ICARE Newsletter Summer 2020

Treatment Advances Among Those with Neurofibromatosis Type 1

There continue to be ongoing advances in treatment studies among those with inherited cancer gene mutations, which are rapidly being followed by FDA approval for specific cancer treatments. Select studies and advances are summarized below:

Neurofibromatosis Type 1 (NF1): 

The FDA granted selumetinib (a MEK inhibitor) breakthrough therapy designation for treatment of inoperable plexiform neurofibromas.




ICARE Newsletter Summer 2020

Treatment Advances Among Those with Lynch Syndrome

There continue to be ongoing advances in treatment studies among those with inherited cancer gene mutations, which are rapidly being followed by FDA approval for specific cancer treatments. Select studies and advances are summarized below:

Lynch Syndrome: 

Colorectal Cancer: Among patients with MSI-H or MMR-deficient colorectal cancers (frequently seen among those with Lynch syndrome), pembrolizumab (an immunotherapy drug) improved survival [1], which then led to subsequent FDA approval of its use as first-line treatment in unresectable or metastatic, MSI-H or MMR-deficient colorectal cancer.

Endometrial Cancer: Among women with MMR-deficient endometrial cancer, a recent study showed potential benefit from avelumab (an immunotherapy drug) [2].

[1] Andre, et al. ASCO Meeting. 2020 May. Available at: https://meetinglibrary.asco.org/record/186928/abstract; [2] Konstantinopoulos, et al. J Clin Oncol. 2019 Aug. PMID: 31461377




ICARE Newsletter Summer 2020

Treatment Advances Among Those with Von-Hippel Lindau (VHL) Disease

There continue to be ongoing advances in treatment studies among those with inherited cancer gene mutations, which are rapidly being followed by FDA approval for specific cancer treatments. Select studies and advances are summarized below:

Von-Hippel Lindau (VHL) Disease: 

Among patients with VHL-associated clear cell renal cell carcinoma (RCC), a recent study suggested potential benefit from MK-6482, which subsequently led to the FDA breakthrough therapy designation for those with nonmetastatic RCC tumors < 3 cm in size.

Jonasch, et al. J Clin Oncol. 2020 May. Available at: https://tinyurl.com/jonasch2020




ICARE Newsletter Summer 2020

Treatment Advances Among BRCA1/2 Carriers

There continue to be ongoing advances in treatment studies among those with inherited cancer gene mutations, which are rapidly being followed by FDA approval for specific cancer treatments. Select studies and advances are summarized below:

BRCA1/2 Carriers: 

Breast Cancer: For those with later stage or metastatic breast cancer, the FDA currently has approvals for the use of PARP inhibitors, yet the impact of combination therapy is still under investigation. A recent study suggested veliparib (a PARP inhibitor) in combination with chemotherapy showed benefit [1]. For those with early stage breast cancer, a recent study suggested benefit from talazoparib (another PARP inhibitor) [2]. New research suggests that platinum-based agents, which have been suggested to be of particular benefit to treat BRCA1/2-related breast cancer, are less effective than previously thought in the neoadjuvant setting (treatment given before surgery) [3], and among those with early stage triple negative breast cancer in the neoadjuvant setting [4].

Ovarian Cancer: For those with advanced ovarian cancer, the FDA recently approved niraparib (a PARP inhibitor) as first-line maintenance treatment. Among those with platinum-sensitive relapsed ovarian cancer who had received at least two prior lines of platinum-based chemotherapy, olaparib (another PARP inhibitor) showed potential benefit [5]. Subsequently, the FDA approved olaparib as first-line maintenance treatment in those with complete or partial response to first-line platinum-based chemotherapy.

Prostate Cancer: Among those with metastatic castration-resistant prostate cancer, a recent study suggested that rucaparib (a PARP inhibitor) may have antitumor activity [6], which then provided data to support FDA approval of rucaparib among those treated with anti-androgens and/or other treatments. Olaparib (another PARP inhibitor) also received FDA approval recently for a similar indication.

Pancreatic Cancer: Among BRCA1/2 or PALB2 carriers with stage 3 or 4 pancreatic cancer, the addition of veliparib (a PARP inhibitor) did not provide additional benefit over cisplatin and gemcitabine alone [7].

[1] Dieras, et al. ESMO 2019 Congress. 2019 Sep. Available at: https://tinyurl.com/dieras2019; [2] Litton, et al. J Clin Oncol. 2020 Feb. PMID: 31461380; [3] Tung, et al. J Clin Oncol. 2020 May. PMID: 32097092; [4] Pohl-Rescigno, et al. JAMA Oncol. 2020 Mar. PMID: 32163106; [5] Penson, et al. J Clin Oncol. 2020 Feb. PMID: 32073956; [6] Abida, et al. J Clin Oncol. 2020 Aug. PMID: 32795228; [7] O’Reilly, et al. J Clin Oncol. 2020 May. PMID: 31976786; 




ICARE Social Media Post July 2020

BRCA1/2 and Other Gene Carriers with Breast Cancer Don’t Always Receive Recommended Treatment

BRCA1/2 and other gene mutation carriers with early stage breast cancer are not always receiving cancer treatment as recommended by national guidelines.

Even though more and more people have been tested for hereditary cancer over the years, using this information accurately to guide treatment has not been as successful.

These findings highlight the need for using this information better to help guide appropriate breast cancer treatment, including radiation treatment and chemotherapy.

Check out the full article at https://jamanetwork.com/journals/jamaoncology/fullarticle/2760433.




ICARE Social Media Post June 2020

Advances in Treatment for Colorectal Cancer

On June 29, 2020, the FDA approved the use of Keytruda (pembrolizumab), as first-line treatment in unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer.

Among people with Lynch syndrome, the risk for colorectal cancer (which often has microsatellite instability and/or mismatch-repair deficiency) is raised.

Keytruda (pembrolizumab) showed to double the progression-free survival in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer.

The recent FDA approval to use Keytruda (pembrolizumab) as first-line treatment for microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer represents another strategy to improve treatment of individuals with Lynch syndrome and unresectable or metastatic colorectal cancer.

Check out the news release: https://www.fda.gov/news-events/press-announcements/fda-approves-first-line-immunotherapy-patients-msi-hdmmr-metastatic-colorectal-cancer




ICARE Social Media Post June 2020

Advances in Treatment for BRCA-Mutated Triple Negative Breast Cancer

In a study of 914 women with different breast cancer subtypes, overall pathologic complete response rates were:

  • Higher in those with BRCA1/2 mutations (60.4% versus 46.7%)
  • No differences were seen in those with mutations in other inherited cancer genes
  • Among patients with triple-negative breast cancer, BRCA1/2 mutations had highest response rates to treatment in both study arms (Arm 1: 74.3%, Arm 2: 64.7%) compared to non-carriers (Arm 1: 47%; Arm 2: 45%)
  • Among those without triple negative disease, BRCA1/2 carriers had higher response rates compared to non-carriers (31.8% vs 11.9%)
  • Both platinum-based and non-platinum-based treatment may be of benefit to BRCA1/2 carriers with triple negative breast cancer in the neoadjuvant setting, but additional studies are needed to further evaluate these findings

Check out the original article at: https://jamanetwork.com/journals/jamaoncology/article-abstract/2762579




ICARE Social Media Post June 2020

Advances in BRCA1/2 Breast Cancer Treatment

Through a randomized phase 2 study (called the INFORM trial) among BRCA1/2 carriers with breast cancer, cisplatin was no better in inducing pathologic complete remission compared to AC. The pathologic complete remission rate was 18% for cisplatin and 26% for AC. Cisplatin is not better than other chemotherapy for induction therapy for breast cancers in BRCA1/2 mutation carriers.

This study corrects data from prior studies, some of which were observational studies prone to bias. Specifically, results from this trial provides new information which suggests less efficacy of platinum-based therapies than previously thought. This information should be considered when choosing the best treatment for these women.

Check out original article at https://ascopubs.org/doi/pdf/10.1200/JCO.19.03292.

Check out ASCO’s commentary at: https://www.ascopost.com/issues/february-25-2020/neoadjuvant-cisplatin-for-brca-mutation-carriers-pruning-the-dead-branches/




ICARE Social Media Post June 2020

Advances in Treatment for Pancreatic Cancer: Cisplatin + Gemcitabine

In BRCA1/2 or PALB2 carriers with stage 3 or 4 pancreatic cancer, the combination of cisplatin + gemtricitabine with veliparib (a PARP inhibitor), did NOT seem to provide additional benefit over cisplatin + gemtricitabine alone.

Through this phase 2 randomized control trial, response rates in both treatment arms were high with similar overall survival rates. The take-home point is that the cisplatin/gemcitabine regimen showed a tremendous response for these patients (and veliparib did not really provide additional benefit). Additional trials are ongoing to study these drugs further in pancreatic cancer patients.

Check out the full article at https://www.ncbi.nlm.nih.gov/pubmed/31976786




ICARE Social Media Post May 2020

Platinum Based Chemotherapy for Metastatic Pancreatic Cancer

A recent study found that patients with metastatic pancreatic cancer who had mutations in the DNA repair genes (either inherited or just in the tumor) had better clinical outcomes after platinum-based chemotherapy compared to patients without these mutations.

Check out the link to full article: https://clincancerres.aacrjournals.org/content/early/2020/05/20/1078-0432.CCR-20-0418




ICARE Social Media Post May 2020

Advances in Treatment for Metastatic Prostate Cancer: Olaparib

On May 19, 2020 the FDA approved the use of olaparib (Lynparza) as treatment in BRCA and other gene carriers (homologous recombination repair genes) with metastatic castration-resistant prostate cancer who have been treated with enzalutamide or abiraterone.

Link to full article: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-hrr-gene-mutated-metastatic-castration-resistant-prostate-cancer




ICARE Social Media Post May 2020

Advances in Treatment for Metastatic Prostate Cancer: Rucaparib

On May 15, 2020 the FDA approved the use of rucaparib (Rubraca) as treatment in BRCA carriers with metastatic castration-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.

Link to full article: https://www.fda.gov/drugs/fda-grants-accelerated-approval-rucaparib-brca-mutated-metastatic-castration-resistant-prostate




ICARE Social Media Post May 2020

Advances in Ovarian Cancer Treatment for BRCA1/2 Carriers: Olaparib & bevacizumab

On May 8, 2020 the FDA approved the use of olaparib (Lynparza) as first-line maintenance treatment in BRCA1/2 carriers (deleterious or suspected deleterious mutations) and/or a genomic instability, with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.

Link to full article: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-plus-bevacizumab-maintenance-treatment-ovarian-fallopian-tube-or-primary




ICARE Social Media Post May 2020

Advances in Ovarian Cancer Treatment for BRCA1/2 Carriers: Olaparib

In recognition of World Ovarian Cancer Day, we’d like to share some exciting results from a study of women with ovarian cancer and a BRCA mutation:

In a recent phase III trial, olaparib (PARP inhibitor) showed improved response and progression-free survival compared with chemotherapy (without platinum) in BRCA carriers with platinum-sensitive relapsed ovarian cancer who had received at least two prior lines of platinum-based chemotherapy.

Among patients treated with olaparib, the objective response rate was 72.2% compared to only 51.4% for patients treated with chemotherapy only. Additionally, the median progression-free survival was 13.4 months for the olaparib group compared to 9.2 months for the chemotherapy group.

Link to full article: https://ascopubs.org/doi/full/10.1200/JCO.19.02745




ICARE Social Media Post May 2020

Advances in Treatment for Metastatic Prostate Cancer: Olaparib

Findings from a recent study showed that olaparib (PARP inhibitor) significantly improved progression-free survival in patients with BRCA1, BRCA2, or ATM genetic alterations. Benefits were also more broadly seen among patients with homologous recombination repair gene defects.

Link to full article: https://www.nejm.org/doi/full/10.1056/NEJMoa1911440
Check out the ASCO post article at: https://www.ascopost.com/news/may-2020/olaparib-for-patients-with-mcrpc-and-homologous-recombination-repair-gene-alterations/




ICARE Social Media Post April 2020

Advances in Treatment for Ovarian Cancer in BRCA1/2 Carriers: Niraparib

On April 29, 2020 the FDA approved the use of niraparib (Zeluja) as first-line maintenance treatment in BRCA1/2 carriers with advanced ovarian cancer!

More details available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer




ICARE Social Media Post April 2020

Treatment Patterns in Women with Inherited Breast Cancer

Results from a population-based study of over 20,000 women from SEER registries of Georgia and California diagnosed with stage 0 to stage III breast cancer between 2014 and 2016 tested for inherited breast cancer were recently published. Findings suggest that women who test positive for certain mutations receive certain patterns of treatment. These patterns of treatment may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.

Specifically, results from the study suggested that among women with inherited breast cancer gene mutations suggest:

– undertreatment with radiotherapy (i.e., lower use of post-lumpectomy radiotherapy in those in whom this would be indicated)

-overtreatment with chemotherapy (i.e., greater use of chemotherapy in those eligible to consider omitting this treatment (e.g., early-stage, ER/PR-positive disease))

-overtreatment with bilateral mastectomy (i.e., greater use of bilateral mastectomy in women eligible for unilateral surgery)

Check out the full article at https://jamanetwork.com/journals/jamaoncology/article-abstract/2760433




ICARE Social Media Post March 2020

Cancer Treatment in Childhood and Treatment-Associated Polyposis

Treatment-associated polyposis (TAP) should be considered in patients who develop many colon polyps after treatment for a childhood or young adulthood cancer but do not have an identified mutation in a hereditary cancer gene.

A recent study reported that 35% of patients with TAP developed over 50 colorectal polyps, and 94% had multiple types of polyps, including adenomas, serrated polyps, hyperplastic polyps, and hamartomas.

Check out the full article at https://cancerpreventionresearch.aacrjournals.org/content/early/2020/02/09/1940-6207.CAPR-19-0416




ICARE Social Media Post February 2020

Advances in Treatment: Plexiform Neurofibromas in NF1

The FDA has granted a breakthrough therapy designation to selumetinib, a MEK inhibitor, for treatment of inoperable plexiform neurofibromas.

These types of neurofibromas are almost exclusively seen in individuals with neurofibromatosis type 1 (NF1). These plexiform neurofibromas are benign tumors on the nerve sheaths and can develop anywhere in the body. These tumors typically cause morbidities such as pain, motor dysfunction, disfigurement, and more, and can surround internal organs. Approximately 5-10% can transform to malignant peripheral nerve sheath tumors. Although many of them can be removed through surgery, there are some that are inoperable.

A recent study showed that most patients with inoperable plexiform neurofibromas had some benefit with treatment with selumetinib which may represent a tremendous treatment advance for these individuals.

Check out more information about this study at https://ccr.cancer.gov/news/article/mek-inhibitor-selumetinib-granted-breakthrough-designation-by-fda-to-treat-neurofibromatosis-type-one-in-pediatric-patients




ICARE Social Media Post February 2020

Genetic Testing in Tumors versus Genetic Testing for Cancer Risk

There are different types of genetic/DNA tests offered to patients with cancer:

1) Tumor tests, mainly done to guide cancer treatment.

2) Blood or saliva tests (on normal DNA that individual was born with) to identify inherited cancer predisposition, which may also guide cancer treatment in some instances.

Genetic testing of the tumor detects mutations found in the tumor tissue itself and helps select the appropriate treatment. Genetic testing for hereditary cancer is done on normal DNA (DNA a person was born with) which is found in every cell of the body. Mutations found in normal DNA can detect an inherited predisposition to cancer and provides information for at-risk relatives.

A recent study of individuals with cancer who enrolled in a clinical trial for genetic testing of the tumor, revealed that although most knew that the results would be used to select their cancer treatment, a very small number knew that the test would NOT provide information about their future cancer risks or cancer risks to their family members.

This highlights the importance of focusing on improving the level of genetic health literacy of the public. Check out the article at https://healthitanalytics.com/news/cancer-patients-have-limited-understanding-of-genomic-test-results




ICARE Newsletter Winter 2020

Treatment Advances Among Those with Inherited Prostate Cancer Predisposition

A recent study reported a high complete response rate among men with a BRCA1/2 mutation with metastatic, castration-resistant prostate cancer who were treated with niraparib (a PARP inhibitor) of 63% compared to 17% in the non-BRCA1/2 group.1 Based on this data, the Federal Drug Administration (FDA) granted breakthrough therapy designation to niraparib on October 3, 2019 to expand the treatment options for men with BRCA1/2 positive, metastatic, castration-resistant prostate cancer.2

1Smith, et al. Presented at 2019 ESMO Congress. 2019 Sept-Oct. Barcelona, Spain. Abstract LBA50. 2Augenstein S. FDA Grants Breakthrough Therapy Designation to Niraparib for mCRPC. 2019 Oct. Available at: https://tinyurl.com/BRCAassociatedprostatecancer.

Social media post: https://tinyurl.com/ICARE20191220




ICARE Newsletter Winter 2020

Treatment Advances Among Those with Inherited Pancreatic Cancer Predisposition

Results from a recent study showed olaparib (a PARP inhibitor) nearly doubled the progression-free survival in BRCA1/2 carriers with metastatic pancreatic cancer.1 Based on this data, the FDA approved the use of olaparib as a first-line maintenance treatment in BRCA1/2 carriers with metastatic, platinum-sensitive pancreatic cancer. This represents another treatment advance in pancreatic cancer and highlights the importance of genetic testing for all patients with pancreatic cancer.

Another recent study among pancreatic cancer patients with a BRCA1/2 or PALB2 mutation showed that response rates after first line treatment with cisplatin/gemcitabine alone was 65.2%, and with addition of veliparib (a PARP inhibitor), it was 74.1%.2 The study evaluated each arm separately and did not compare them. Survival at 2 years and 3 years was also encouraging at 31% and 18%, respectively. These data highlight the importance of conducting testing for inherited cancer among all patients with pancreatic cancer, as this information may guide treatment among those identified to have inherited cancer gene mutations such as BRCA1/2 or PALB2.

1Golan, et al. N Engl J Med. 2019 Jul. PMID: 31157963; 2Helwick, C. The ASCO Post. 2020 Jan. Available at: https://www.ascopost.com/  

Social media post: https://tinyurl.com/ICARE202013  




ICARE Social Media Post January 2020

Advances in Treatment for Lynch Syndrome-Related Endometrial Cancer

A recent phase II study showed increased response to an immunotherapy drug (avelumab), in women with endometrial cancer with mismatch repair deficiency.

Among women with Lynch Syndrome, the risk for endometrial cancer (which often has mismatch repair deficiency) is raised. This new study shows promising treatment options for women with endometrial cancer and Lynch syndrome with recurrent or persistent endometrial cancer.

Check out the full article at the Journal of Clinical Oncology: https://lnkd.in/embydpk




ICARE Social Media Post January 2020

Celebrating 10 Years of ICARE

 

Happy New Year! 2020 represents a decade for ICARE

We are celebrating 10 years of research, education, and engagement, through which we have enrolled nearly 3500 participants, including over 2000 gene mutation carriers, disseminated 15 newsletters, led and collaborated on multiple research projects, and impacted individuals affected by inherited cancer predisposition all over the world.

Let’s take a quick look at what’s happened in the last decade:

2010ICARE was launched.

2012 – First commercially available gene panel test for inherited cancer became available, and ICARE reached 1000 study participants! Cost of testing just for BRCA1 and BRCA2 was over $4000.

2013 –The Supreme Court invalidated the BRCA patent which allowed expanded use of multi-gene panel testing as the BRCA genes could then be added to the panel tests.

2015 – FDA approved the use of PARP inhibitors for BRCA carriers with ovarian cancer which improved treatment options.

2016ICARE reached 1000 BRCA carriers and 2000 study participants!

2017 – The FDA approved immunotherapy treatment for mismatch repair-deficient cancers, which was an important advance for individuals with Lynch syndrome.

2019ICARE reached 3000 study participants!

2020 – Ongoing discovery of new cancer genes and improved technology continues to drive cost of genetic tests down to as low as $250 and lower!

Thank you for your continued support in helping us fulfill our mission to end the cycle of inherited cancer through research, education, and engagement!




ICARE Social Media Post January 2020

Advances in Treatment for Pancreatic Cancer in BRCA Carriers

The FDA approved the use of olaparib, a PARP inhibitor, as first-line maintenance treatment in BRCA1/2 carriers with metastatic, platinum-sensitive, pancreatic cancer.

Platinum-sensitive cancer is a cancer that responds to treatment with drugs that contain the metal platinum, such as carboplatin or cisplatin. Olaparib showed to nearly double the progression-free survival in BRCA1/2 carriers with metastatic pancreatic cancer.

The recent FDA approval to use olaparib as first-line maintenance treatment for BRCA carriers with metastatic pancreatic cancer represents another strategy to improve treatment of pancreatic cancer. It also demonstrates the importance of genetic testing for ALL patients with pancreatic cancer (because it will tell us who has a BRCA mutation, which may then make them eligible for PARP inhibitor treatment).

Check out the articles at: https://www.ncbi.nlm.nih.gov/pubmed/?term=Maintenance+Olaparib+for+Germline+BRCA-Mutated+Metastatic+Pancreatic+Cancer

-OR-

https://www.healio.com/hematology-oncology/gastrointestinal-cancer/news/online/%7B3235fd91-3983-444f-b51e-39a111619a12%7D/maintenance-olaparib-significantly-delays-progression-of-brca–mutated-pancreatic-cancer




ICARE Social Media Post December 2019

Evaluation of PARP Inhibitors in BRCA-Associated Prostate Cancer

The FDA granted breakthrough therapy designation to niraparib (a PARP inhibitor) for the treatment of men with BRCA1/2 positive, metastatic castration-resistant, and heavily pre-treated prostate cancer.

Results from a recent study show a 63% complete response rate in men with BRCA1/2 positive, metastatic castration-resistant prostate cancer treated with niraparib compared to 17% in the non- BRCA group.

Previously, niraparib was approved for ovarian cancer. This treatment can help address lack of treatment options for men with BRCA1/2 positive, metastatic castration-resistant prostate cancer.

Check out the articles at https://www.cancernetwork.com/fda/fda-grants-breakthrough-therapy-designation-niraparib-mcrpc and https://www.healio.com/hematology-oncology/prostate-cancer/news/online/%7B22878907-82bd-408e-b99f-b51c50d8c467%7D/fda-grants-breakthrough-therapy-designation-to-zejula-for-prostate-cancer-subtype.




ICARE Featured Video December 2019

NCCN Genetic/Familial Breast, Ovarian, and Pancreatic Guidelines

Below you may watch a featured video from the December 2019 Genetics Case Conference, which outlined updates to the National Comprehensive Cancer Network (NCCN) guidelines.

 




ICARE Social Media Post December 2019

Patient Reported Outcomes In A Study of PARP Inhibitors in BRCA Carriers with Metastatic Breast Cancer

Did you know? PROs are impacting treatment advances in metastatic breast cancer. Olaparib increased progression-free survival among BRCA carriers with metastatic HER2- breast cancer. Thanks to patient reported outcomes, a new study now suggests it also improved patients’ quality of life!

Check it out the new article published in October 2019 directly at https://www.ncbi.nlm.nih.gov/pubmed/31446213!




ICARE Social Media Post October 2019

Advances in Treatment for Advanced Breast Cancer in BRCA Carriers

Monotherapy with PARP inhibitors is FDA-approved for patients with metastatic breast cancer with BRCA mutations. BUT, does adding additional drugs (called ‘combination therapy’) help?

In BRCA carriers with metastatic breast cancer, the combination of veliparib AND chemotherapy with platinum-based agents (carboplatin) and taxanes (paclitaxel) led to a longer duration of progression free survival (disease that did not progress), compared to those treated with ONLY chemotherapy. The duration of progression free survival was DOUBLE with veliparib/chemotherapy 3 years after treatment.

Additional information can be found at ESMO 2019’s BROCADE 3 abstract.




ICARE Social Media Post October 2019

Advances in Early Stage Breast Cancer Treatment for BRCA Carriers

New benefits from a PARP inhibitor, talazoparib, among BRCA carriers with early stage breast cancer. The current FDA approvals for the use of PARP inhibitors is limited to women with metastatic (stage IV) breast cancer. These drugs are being tested in early stage breast cancer to shrink down the tumor (called neoadjuvant treatment) before surgery to remove it.

Specifically, 6 months of neoadjuvant talazoparib monotherapy (treatment with only talazoparib) resulted in significantly improved rates of complete response in patients with operable (stage I-III) breast cancer.

Check out the full article at: https://pubmed.ncbi.nlm.nih.gov/31461380/

You can also look for other treatment advances in BRCA carriers in our newsletters at https://inheritedcancer.net/newsletters/.




ICARE Newsletter Summer 2019

Ovarian Cancer Treatment Advances for BRCA1/2 Carriers

A recently reported study of women with ovarian cancer and homologous recombination deficiency (HRD) who received a PARP inhibitor (niraparib) as fourth line or later treatment showed potential clinical benefit. Specifically, median overall survival after treatment was 19 months in the HRD-positive group (including those with BRCA1/2 mutations) compared to 15.5 months in the HRD-negative group. In fact, the subgroup with BRCA1/2 mutations had a median overall survival of 26 months. These results suggest possible expansion for use of this class of drugs beyond those with BRCA1/2 mutations to a broader patient population with HRD-positive ovarian cancer.

Moore, et al. Lancet Oncol. 2019 May. PMID 30948273.




ICARE Newsletter Summer 2019

Pancreatic Cancer Treatment Advances for BRCA1/2 Carriers

Results from a clinical trial of individuals with a BRCA1/2 mutation and pancreatic cancer showed that patients who received a PARP inhibitor (olaparib) for maintenance treatment had almost half the risk of their disease progressing when compared to receiving a placebo.1 In fact, after 2 years, 22.1% of patients who received olaparib had no disease progression compared to 9.6% of those receiving a placebo.1 In October 2018, Lynparza (olaparib) received orphan drug designation for pancreatic cancer through the U.S. Food and Drug Administration. Another study of a PARP inhibitor called rucaparib, presented at the 2019 AACR meeting, showed that BRCA1/2 or PALB2 carriers with advanced, platinum-sensitive, pancreatic cancer seemed to benefit from this maintenance treatment.2 In fact, of the 19 patients assessed so far, one had a complete response and six had a partial response to the treatment.2 These results remain preliminary and require more proof that they are true, but represent another possible treatment advance for those with pancreatic cancer and BRCA1/2 or PALB2 mutations. These results also highlight the importance for both germline (inherited) and tumor (somatic) testing among patients with pancreatic cancer.

1Golan, et al. N Engl J Med. 2019 July. PMID 31157963.
2Reiss Binder, et al. Abstract CT234. AACR Annual Meeting, presented 2019 April.




ICARE Newsletter Summer 2019

Prostate Cancer Treatment Advances for BRCA1/2 Carriers

There is now information to suggest that identifying inherited mutations in DNA repair genes, such as BRCA1/2 and other genes, in men with metastatic prostate cancer may open doors for other treatment options. Results of a phase 2 clinical trial among men with metastatic and heavily pre-treated prostate cancer were presented at the American Society of Clinical Oncology 2019 meeting.1 Mateo and colleagues found that treatment with a PARP inhibitor (olaparib) was promising among those with BRCA1/2 mutations (24 of 30 patients) and PALB2 mutations (4 of 7 patients), while patients with other inherited genes also showed some response.1 Another recent study suggested that men with metastatic prostate cancer and a BRCA2 mutation who received androgen blockers for their initial treatment had better outcomes compared with those who received taxanes.2 This suggests that BRCA2 status may guide initial treatments among metastatic prostate cancer patients.2

 1Mateo, et al. J Clin Oncol. 2019 May. DOI: 10.1200/JCO.2019.37.15_suppl.5005.
 2Castro, et al. J Clin Oncol. 2019 Feb. PMID 30625039.




ICARE Newsletter Winter 2019

Other Advances in Cancer Treatment Among Cancer Patients with Inherited Disease: Familial Adenomatous Polyposis (FAP)

A new drug (sorafenib) showed promising results among patients with desmoid tumors, which are a type of tumor for which patients with Familial Adenomatous Polyposis (FAP) due to APC gene mutations are at risk. These tumors frequently grow and encompass internal organs and can be hard to remove surgically. The newly published research showed that treatment with sorafenib doubled the rate of progression-free survival at 2 years among patients with advanced or refractory desmoid tumors. The drug also reduced the risk of death by 87% compared to the placebo, with no major safety concerns. These advances serve to highlight some of the recent breakthroughs in the treatment of tumors among those with inherited cancer predisposition.

Gounder MM, et al. N Engl J Med. 2018 Dec 20. doi: 10.1056/NEJMoa1805052.




ICARE Newsletter Winter 2019

Other Advances in Cancer Treatment Among Cancer Patients with Inherited Disease: Lynch Syndrome

Pertaining to metastatic prostate cancer, recently published data reported 8.1% of men with advanced prostate cancer had evidence of mismatch repair (MMR) mutations in their tumors. These types of mutations are frequently seen in tumors among Lynch syndrome patients. In addition, men with this type of tumor had much poorer survival. Tumors with MMR defects are thought to generate more antigens and be more responsive to a new class of drugs called immunotherapy. The researchers are now planning to conduct a new clinical trial to test the effectiveness of immunotherapy (through checkpoint inhibitors) in this group of patients with particularly aggressive prostate cancer. These advances serve to highlight some of the recent breakthroughs in the treatment of tumors among those with inherited cancer predisposition.

Nava Rodrigues D, et al. J Clin Invest. 2019 Oct 1. PMID: 30179225.




ICARE Newsletter Winter 2019

Other Advances in Cancer Treatment Among Cancer Patients with Inherited Disease: von Hippel-Lindau (VHL) Disease

Additional exciting advances include the results of a new drug (pazopanib) to treat an inherited cancer condition called von Hippel-Lindau Disease (VHL), in which patients are predisposed to kidney cancers, pancreatic tumors, and hemangioblastomas (i.e., tumors involving the blood vessels). Study results showed that among 31 patients with VHL, overall response rate with the drug was 42%, with responses of 52% for renal cell carcinomas, 53% for pancreatic lesions, and 4% for CNS hemangioblastomas. Results are encouraging, and this may be a treatment option for individuals with VHL and growing or unresectable lesions, although safety and activity for these indications warrants further study. These advances serve to highlight some of the recent breakthroughs in the treatment of tumors among those with inherited cancer predisposition.

Jonasch E, et al. Lancet Oncol. 2018 Sept 17. doi 10.1016/S1470-2045(18)30487-X.




ICARE Newsletter Winter 2019

New Research and Approvals of PARP Inhibitor Drugs to Treat Prostate Cancer in BRCA Carriers

Treatment among patients with metastatic castration-resistant prostate cancer: A PARP inhibitor (rucaparib) was granted a breakthrough therapy designation in October 2018 for monotherapy (i.e., sole treatment) among men with metastatic castration-resistant prostate cancer (with a BRCA1/2 mutation) who have received at least one prior androgen receptor-directed treatment and taxane-based chemotherapy. This designation was granted based on results of the phase II TRITON2 study, some results of which have been presented at national meeting, but not yet published.




ICARE Newsletter Winter 2019

New Research and Approvals of PARP Inhibitor Drugs to Treat Breast Cancer in BRCA Carriers

Treatment among patients with advanced or metastatic breast cancer: A PARP inhibitor (talazoparib) was approved by the FDA on October 16, 2018 for BRCA carriers with HER2-negative locally advanced or metastatic breast cancer, based on results of the EMBRACA trial outlined in the last ICARE newsletter.

Litton JK, et al. N Engl J Med. 2018 Aug 23. PMID: 30110579.




ICARE Newsletter Winter 2019

Expansion of Lynch Syndrome Tumor Spectrum Which May Have Treatment Implications

Although the Lynch syndrome tumor spectrum is thought to be limited to cancers of the colorectum, endometrium, ovaries, stomach, and a few other cancer types, a recent article suggested there might be a broader tumor spectrum than previously considered. Furthermore, colorectal and endometrial cancers which develop among Lynch syndrome patients frequently are determined on tumor testing to have high microsatellite instability (MSI-H) or mismatch repair deficiency (MMR-D). The recently published study tested tumors in over 15,000 cancer patients with over 50 cancer types and found that among patients identified to have Lynch syndrome (based on germline DNA testing), 50% had tumors at sites other than the colorectum or endometrium, including urothelial, prostate, pancreas, adrenocortical, small bowel, sarcoma, mesothelioma, melanoma, gastric, and germ cell tumors. The investigators concluded that MSI-H/MMR-D predicts the presence of Lynch syndrome across a much broader tumor spectrum than currently appreciated and suggested that any patient with this tumor characteristic should receive a germline genetic assessment for Lynch syndrome regardless of cancer type or family history. This is particularly important given that Lynch syndrome tumors often respond to a new class of drugs (immunotherapy); thus, this information may help to guide cancer treatments.

Latham A, et al. J Clin Oncol. 2018 Oct 30. PMID: 30376427.




ICARE Newsletter Winter 2019

Refining Treatment for Aggressive Prostate Cancer in Men with BRCA2

A recent study reported that a large proportion of men with aggressive prostate cancer have inherited cancer gene mutations. Specifically, among 400 patients with castration-resistant prostate cancer, 16.2% had a germline mutation in a DNA damage repair gene, including 3% with a BRCA2 mutation. Among BRCA2 carriers, survival was 17.4 months, which was much lower than the 33.2 months observed among non-carriers. Furthermore, the subset of BRCA2 carriers who received first-line treatment with abiraterone or enzalutamide had better outcomes than those who received taxanes. Consequently, these findings suggest that determination of BRCA2 status may help to guide initial treatment of metastatic prostate cancer among BRCA2 carriers, although additional studies are needed to confirm these results.

Castro E, et al. J Clin Oncol. 2019 Jan 9. PMID: 30625039.




ICARE Newsletter Winter 2019

New Research and Approvals of PARP Inhibitor Drugs to Treat Ovarian Cancer in BRCA Carriers

First line maintenance treatment among patients newly diagnosed with advanced ovarian cancer: The results of a trial using a PARP inhibitor (olaparib) as maintenance treatment among ovarian cancer patients with advanced disease, a BRCA mutation, and complete or partial response to platinum-based chemotherapy showed that survival at 3 years was 60% among those who got the drug versus 27% among those who did not. Investigators concluded that among those with successful first-line chemotherapy, “The use of maintenance therapy with olaparib provided a substantial benefit among women with newly diagnosed advanced ovarian cancer and a BRCA mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo.” Soon after publication of these results, on December 19, 2018, the FDA approved olaparib for maintenance treatment of BRCA-mutation advanced ovarian cancer.

Moore K, et al. N Engl J Med. 2018 Dec 27. PMID: 30345884.




ICARE Newsletter Summer 2018

Another PARP-Inhibitor Trial Among BRCA Carriers with Advanced Breast Cancer

In a Phase 3 clinical trial among BRCA carriers with advanced breast cancer, an oral PARP Inhibitor (talazoparib) was compared to standard chemotherapy.  Among those who received the PARP inhibitor, risk of disease progression or death was 46% lower, and the response rate was double. Furthermore, the side effect profile, quality-of-life measures, and breast cancer symptoms were more favorable in the PARP inhibitor group. These findings indicate that talazoparib among this group of patients results in longer progression-free survival than standard chemotherapy, with better patient-reported outcomes.

Litton JK, et al.. N Engl J Med. 2018 Aug 15. PMID: 30110579.




ICARE Newsletter Winter 2018

Advances in the Understanding of Inherited Prostate Cancer

Findings through a recent study reported that inherited cancer gene mutations were present in 8.2% of those with advanced or metastatic prostate cancer, which provides additional support to include this group of men in broader testing, particularly as targeted treatments based on inherited gene mutations becomes increasingly available.1 Another recent study suggested that those with a stronger family history of prostate cancer were more likely to present with more advanced prostate cancer, suggesting that familial or hereditary prostate cancer may be associated with a more aggressive disease.2 In view of these and other recent advances in the understanding about inherited prostate cancers, a group of experts convened to develop a consensus statement to guide the identification, management, and testing of men at risk for inherited prostate cancer.3 Overall, there was broad agreement for discussion of prostate cancer screening among BRCA2 carriers. Furthermore, there was moderate consensus that BRCA2 should be factored into management decisions from an early stage in the patient’s treatment, with stronger consensus that this is very important to consider among those with advanced or metastatic disease. Genetic testing for all men with metastatic castration-resistant prostate cancer regardless of family history was also considered to be important to inform prognosis and targeted therapy, particularly for the BRCA1 and BRCA2 genes, and possibly for the ATM gene.

1Thalgott et al. World J Urol. 2017 Nov 21. PMID:29164326.
2Giri et al. JCO Precision Oncology 2017 May 4;1, 1-17.
3Giri et al. J Clin Oncol. 2017 Dec 13. PMID:29236593.




ICARE Newsletter Winter 2018

Advances in New Treatments for Individuals with Lynch Syndrome

A recently published phase II clinical trial investigated the use of a new class of drugs (called PD-1 Inhibitors) in DNA mismatch repair-deficient/ microsatellite instability-high colorectal tumors (which are features seen in the majority of colorectal tumors from individuals with Lynch Syndrome) among patients with metastatic disease.1 Investigators found patients who received two PD-1 Inhibitors (compared to just one PD-1 inhibitor, which had already shown to be of benefit2) had better response rates which lasted longer while maintaining the safety of the drug. Overall, 50% of these patients did not have progression of their colorectal cancer after 2 years. This treatment strategy represents a promising new option. Additional studies are already underway to evaluate this drug combination as a first line of treatment.

1Overman et al. J Clin Oncol. 2018 Jan 20:JCO2017769901. PMID:29355075.
2Overman et al. Lancet Oncol. 2017 Sep;18(9):1182-1191. PMID:28734759.




ICARE Newsletter Winter 2018

FDA Approval of PARP Inhibitor (Lynparza) for Treatment of Advanced Breast Cancer

On January 12, 2018, the FDA approved the first PARP Inhibitor (Lynparza) for treatment in patients with advanced breast cancer due to inherited BRCA mutations.1 This drug is already approved for certain BRCA carriers for advanced ovarian cancer. PARP inhibitors were originally developed to target the specific pathway through which cancer develops among those with a BRCA mutation. This latest approval demonstrates that developing drugs to target the underlying genetic cause of cancer can be used across cancer types. The approval of this drug was based on a recently published trial which showed that the drug delayed disease progression, which may help preserve quality of life by delaying the use of chemotherapy.2 It remains to be determined whether further improvements in treatment with this drug can be achieved through using it in combination with other drugs.

1https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592347.htm
2Robson et al. N Engl J Med. 2017 Aug 10;377(6):523-533. PMID: 28578601.




ICARE Newsletter Summer 2017

Emerging FDA Approvals of Immunotherapy Among Patients With Metastatic MSI-H Cancers

Over the last few years, immunotherapy has emerged as an exciting new class of drugs. As early as 2015, immunotherapy through PD-1 Inhibitors among patients with MSI-H colorectal cancers was shown to be of potential benefit.1 As many individuals with Lynch Syndrome have cancers that are MSI-H and mismatch repair deficient, this class of drugs was thought to represent a class of ‘targeted treatments’ for individuals with this syndrome.

More recently, the FDA granted accelerated approval for the use of a PD-1 Inhibitor (nivolumab) for the treatment of patients with MSI-H or mismatch repair deficient metastatic colorectal cancer that has progressed after standard treatment through fluoropyrimidine, oxaliplatin, and irinotecan.2 The approval was based on results of the Phase II CheckMate-142 trial, where almost a third of patients who received nivolumab experienced some benefit from it.3 These exciting advances illustrate the expanded treatment options that are being evaluated and approved for those with inherited forms of cancer.

1Le et al. N Engl J Med. 2015 Jun 25;372(26): 2509-20. PMID:26028255.
2https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-receives-fda-approval-opdivo-nivolumab-ms.
3Overman et al. Lancet Oncol. 2017 Jun 19. [Epub ahead of print] PMID: 28734759.




ICARE Newsletter Summer 2017

New Results of a PARP Inhibitor Study Among BRCA Carriers with Metastatic Breast Cancer

Over the last decade, a new class of drugs called “PARP Inhibitors” has been evaluated as a form of targeted treatment among BRCA carriers. Results were recently reported from a Phase 3 clinical trial among BRCA carriers with HER2-negative metastatic breast cancer who received two or less prior chemotherapy regimens for their metastatic disease. Study participants received either the PARP inhibitor (olaparib) or standard treatment, and the primary outcome measured was progression-free survival (i.e. the length of time during and after the treatment where the cancer does not get worse). Of the 302 women who participated in this study, progression-free survival was ~3 months longer among those who received olaparib compared to standard treatment. Side effects from treatment and treatment discontinuation were also lower in the olaparib group.  Furthermore, progression of disease or death was 42% lower among those given olaparib. Although no PARP inhibitor is yet FDA-approved for breast cancer, these results demonstrate the type of evidence needed to move a drug from the clinical trials setting to an FDA-approved treatment and highlight the expansion of personalized treatments among BRCA carriers.

Robson et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Jun 4. PMID: 28578601.




ICARE Newsletter Winter 2017

Newly Approved PARP-Inhibitor (Rucaparib) to Treat BRCA Carriers with Ovarian Cancer

The FDA just approved another PARP inhibitor, rucaparib, for BRCA carriers with ovarian cancer who have already been treated with two or more chemotherapies. Among those with BRCA-mutant ovarian cancers, 54% had a partial or complete response to the drug with a median duration response of 9.2 months. The agency also approved a companion diagnostic test through Foundation Medicine, FoundationFocusTM which may be used in tandem. FoundationFocus CDxBRCA is a tissue-based test that detects tumor BRCA1 and BRCA2 mutations (germline and/or somatic) in ovarian cancer.

What remains interesting is that despite the availability of the companion diagnostic test, FoundationFocus, this test may not be required to determine eligibility for the drug – in fact, those determined to have a germline mutation in BRCA1/2 through any commercial laboratory may be eligible to receive this drug.




ICARE Newsletter Winter 2017

New Study Suggesting BRCA1/2 and ATM Are Associated with Aggressive Prostate Cancer

Among 799 patients with prostate cancer, the rate of BRCA1/2 mutations was much higher among those who passed away of prostate cancer (6.07%) compared to those with low risk disease (1.44%).1 Among the group that died of prostate cancer, those with BRCA1/2 or ATM mutations passed away at an earlier age and had a shorter survival time compared to date of diagnosis. These findings suggest that prostate cancer patients with inherited mutations in BRCA1/2 and ATM have a poorer prognosis, with a higher risk of dying at an earlier age. These results are consistent with results of prior efforts, and highlight the importance of genetic testing among these patients to inform decisions regarding prostate cancer screening and treatment.

1Na R, et al. Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. Eur Urol. 2016 Dec 9. [Epub ahead of print]; PMID: 27989354.




ICARE Newsletter Winter 2017

The Potential Promise of Immunotherapy Targeted to Those with Bi-Allelic Mutations in Lynch Syndrome Genes

People with Lynch Syndrome have a non-working Lynch gene (“mutation”), while the other copy of that gene is normal (recognizing that all of these genes come in pairs, with one member of the pair coming from each parent). Over the last few years, there has been an increased realization that some individuals have a mutation in both copies of their Lynch gene, which leads to a condition called Constitutional Mismatch Repair Deficiency (CMMRD). Those affected with CMMRD often develop cancer in childhood, with the most frequent types of cancer being brain tumors, gastrointestinal (colon or small bowel) cancers, and leukemias.1 Screening guidelines for children with CMMRD, developed through consortium-based efforts, include upper and lower GI scopes and brain imaging in childhood, followed by additional screening in adulthood.2 These efforts form the basis of collecting data to someday develop evidence-based screening guidelines.

Recently, a study of tumors from children with CMMRD showed some unique findings. Specifically, these tumors accumulate mutations at a very high rate (~600 mutations/cell cycle) but do not exceed ~20,000 mutations in <6 months.3 This finding suggests a new mechanism of cancer progression. The exciting component of this is now that the high mutation load and threshold effect are known, this information can be used to target more effective treatments for these cancers. To this end, high mutation load (which also leads to high neoantigen loads) may respond to immune checkpoint inhibition, which is a new class of immunotherapy drugs. In fact, a recent study demonstrated that neoantigen loads of individuals with CMMRD was substantially higher than those without the condition.4 Furthermore, based on this preclinical data, study investigators treated two siblings with CMMRD with recurrent glioblastoma multiforme (a rare and aggressive form of brain cancer) with an immune checkpoint inhibitor (PD-1 inhibitor) called nivolumab, which led to a clinically significant response and substantial shrinkage of the tumor on MRI scans. These findings suggest that cancers with exceptionally high mutation loads may more likely respond to immunotherapy because there is a higher chance they have specific neoantigens which activate T cells. Taken together, it is possible that all CMMRD-related cancers may benefit from this type of treatment approach. To investigate this further, a group of international researchers has developed a pilot study of nivolumab in pediatric patients with hypermutated cancers (clinicaltrials.gov identifier NCT02992964) and anticipates beginning enrolling patients in early 2017.

1Bakry D, et al. Eur J Cancer. 2014 Mar. PMID: 24440087.
2Durno CA, et al. Eur J Cancer. 2015 May. PMID: 25883011.
3Shlien A, et al. Nat Genet. 2015 Mar. PMID:25642631.
4Bouffet E, et al. J Clin Oncol. 2016 Jul 1. PMID: 27001570.




ICARE Newsletter Winter 2016

Potential Use of PARP-Inhibitors Among Men with Prostate Cancer Who Carry a Mutation in BRCA or Other DNA-Repair Gene

A recent study published in the New England Journal of Medicine suggests that PARP-Inhibitors may be of potential use in men who are no longer responding to standard treatments and carry either somatic (i.e., tumor) and/or germline (inherited) mutations in DNA-repair genes (i.e., BRCA1/2, ATM, Fanconi Anemia genes and CHEK2).1 Of 49 men with prostate cancer evaluated through the study, 16 (33%) had somatic mutations in DNA-repair genes.  Of these 16 patients, 14 (88%) responded to the PARP-inhibitor drug (Olaparib), including all 7 patients with BRCA2 mutations (3 with germline mutations and the other 4 with somatic mutations only) and 4 of the 5 ATM mutation carriers. These findings further demonstrate the potential importance of PARP-inhibitors among men with DNA-repair gene mutations in their prostate cancers; however, further studies are needed before these drugs can be considered for routine clinical use.

1Mateo J, et al. NEJM. 2015 Oct 29;373(18):1697-708. PMID: 26510020.




ICARE Newsletter Summer 2015

Advances in Preventive and Treatment Approaches for Individuals with Lynch Syndrome

A study of over 1800 individuals with a mutation in one of the Lynch Syndrome genes was recently completed to assess whether aspirin and ibuprofen use may reduce colon cancer risk. Results showed that in those who took aspirin or ibuprofen for between 1 month and 4.9 years, the colon cancer risks were lower than those with less than one month of use.  This study provides additional evidence that both aspirin and ibuprofen may be an effective strategy to help reduce colorectal cancer risk among those with Lynch syndrome, where individuals currently rely solely on frequent colonoscopies for risk reduction. We encourage patients to speak with their healthcare provider about this study to determine if the addition of these medications would be right for them.

Pertaining to treatment of colorectal cancers, a new class of drugs that target the immune system (called PD-1 Inhibitors) has been shown to have potential efficacy in colorectal cancers with the MSI-H phenotype.  Given that most colorectal cancers in individuals with Lynch syndrome are MSI-H, this drug could potentially represent a targeted treatment for these individuals.  However, prior to becoming standard treatment in the clinical setting, clinical trials are needed.  These are currently being conducted to evaluate PD-1 inhibitors in individuals with MSI-H colorectal cancers. As clinical trials continue, we will monitor this exciting advancement for individuals with Lynch Syndrome.

 Ait Ouakrim D et al. Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. J Natl Cancer Inst. 2015 Jun 24;107(9). PMID: 26109217




ICARE Newsletter Winter 2015

The First PARP-Inhibitor to Be Approved for Clinical Use in BRCA Carriers

More frequently, cancer drugs are being developed to treat tumors based on their molecular make-up. PARP inhibitors are the first class of drugs specifically developed to treat BRCA-related tumors through targeting the DNA repair pathway. The PARP Inhibitors target this pathway and cause cancer cells to die while healthy cells are spared.

Although PARP inhibitors were developed almost a decade ago, they were only recently approved for clinical use through the U.S. Food and Drug Administration (FDA) after extensive evaluation through clinical trials. Specifically, the PARP inhibitor called Olaparib (Lynparza) was approved for use in BRCA carriers with advanced ovarian cancer treated with three or more prior lines of chemotherapy. 

The effectiveness of this PARP inhibitor, Olaparib, was examined in a study of 137 women with BRCA mutations and advanced ovarian cancer. Results showed that about a third of patients had partial shrinkage or complete disappearance of their ovarian tumor for an average of 8 months. These findings led the FDA to grant accelerated approval of this drug to treat life-threatening disease (because results of the clinical trial showed likely clinical benefit to patients).

Olaparib constitutes the first of a new class of drugs (i.e., PARP inhibitors) for treating ovarian cancer. This drug serves as an example of how the understanding of the underlying molecular mechanisms by which cancer develops can lead to more personalized and effective treatments.

There are many open clinical trials that continue to evaluate PARP inhibitors to determine: 1) when to start treatment with these agents in ovarian cancer patients; 2) whether they work in other BRCA-associated cancers such as breast cancer, pancreatic cancer and prostate cancer (among others); and 3) whether they may also be of benefit to individuals without germline BRCA mutations. Thus it is important to continue evaluating these drugs through clinical trials to determine how they may be best used to treat and perhaps prevent cancer.




ICARE Newsletter Winter 2014

Contralateral Mastectomy May Improve Survival in BRCA Mutation Carriers

It has been established that women who carry a germline BRCA mutation face breast cancer risks of 60-70% in their lifetime. After an initial breast cancer diagnosis, these women face a high risk for contralateral breast cancer. Some women with BRCA mutations move forward with contralateral mastectomy when they develop their first breast cancer diagnosis (as part of their breast cancer treatment); however it remains unclear whether contralateral mastectomy reduced the breast cancer-related mortality in these women. Recently, Dr. Kelly Metcalfe published a study1 based on 390 women with stage I or II breast cancer and a BRCA mutation followed for up to 20 years from diagnosis.  Of these women, 209 were treated with unilateral mastectomy compared to 181 treated with bilateral mastectomy. Results indicated that women with BRCA-associated breast cancer treated with bilateral mastectomy were 48% less likely to die of breast cancer within 20 years of diagnosis than women treated with unilateral mastectomy (even after controlling for age).  This is among the largest and longest running studies to evaluate long-term survival of BRCA-associated breast cancers, comparing type of surgery at initial diagnosis. Study findings suggest that bilateral mastectomy should be discussed as an option for young women with a BRCA mutation and early stage breast cancer. However, despite the long follow-up and large sample size, further research is needed to confirm these findings given the small numbers of “events” (i.e., second breast cancers) in participants. Ultimately, emerging data on personalized chemotherapeutic and biologic treatments for BRCA-related breast cancers coupled with study findings suggest that women with newly-diagnosed breast cancer might benefit from the knowledge that they carry a BRCA mutation.

Metcalfe et al. 2014 BMJ. 2014 Feb 11;348:g226. PMID: 24519767




ICARE Newsletter Summer 2013

Male BRCA Carriers Have Poorer Outcomes from Prostate Cancer

Over the last few years, a number of studies have suggested that men with germline BRCA mutations (especially BRCA2) have poorer outcomes when they develop prostate cancer. In fact, a recent study of 2019 patients with prostate cancer, including 18 BRCA1 carriers, 61 BRCA2 carriers, and 1940 noncarriers indicated that germline mutations were more frequently associated with: higher Gleason score, later stage (T3/T4), nodal involvement, and metastatic disease present at diagnosis. Thus, these findings suggest that when men with BRCA mutations develop prostate cancer, it is more likely to be an aggressive subtype of the disease which may be related to the poorer outcomes observed. Consequently, study authors suggested that consideration should be given for tailoring clinical management for these patients, especially because most BRCA carriers with prostate cancer are currently treated through following the same protocols used for noncarriers (due to lack of studies focused on evaluating tailored management strategies in this group of men).

Furthermore, although clinical trials in this group are needed, authors suggested the following as a consideration: “radical treatment with either surgery or radiotherapy seems to be preferable to active surveillance for these patients, even for cases classified as low risk.”

Castro et al. J Clin Oncol. 2013 May 10;31(14):1748-57.




ICARE Newsletter Winter 2013

The Selection of Chemotherapy in BRCA Patients with Pancreatic Cancer

Some evidence suggests that individuals with BRCA mutations who develop pancreatic cancer may benefit from specific chemotherapy regimens. In a recent review of this topic, Kim et al reported on a study of 5 patients with BRCA mutations (4 BRCA2 and 1 BRCA1) who were treated with a platinum-based chemotherapy regimen.1 Of these patients, 3 had advanced disease and all had some response to platinum; an additional 2 patients had resectable and locally advanced disease, both of whom were downstaged after receiving platinum as part of their treatment and eventually underwent resection of their tumor. Another study was conducted based on 15 BRCA carriers with pancreatic cancer.2 Of these patients, 4 received a PARP inhibitor alone or in combination with chemotherapy, of which 3 demonstrated an initial radiographic response and one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy as first line treatment for metastatic disease, of whom five had a radiographic partial response.

These studies add to the limited literature to suggest that therapeutic agents that target DNA repair (e.g., PARP inhibitors, Platinum-based agents) may offer benefit when treating BRCA-associated pancreatic cancers, even in advanced stages. However, the numbers reported remain very small and it is critical to perform prospective studies in individuals with BRCA-associated pancreatic cancers to truly determine the efficacy of targeted therapies.   

1. Kim R, et al. JOP. 2012 Mar 10;13(2):180-1. 2. Lowery MA, et al. Oncologist. 2011;16(10):1397-402.