ICARE Social Media Post December 2020

Cost-Effectiveness of Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer

For further information, read the article available at: https://jnccn.org/…/journals/jnccn/18/11/article-p1528.xml



ICARE Social Media Post December 2020

PALB2-associated Metastatic Breast Cancer

For further information, view the article at: https://ascopubs.org/doi/abs/10.1200/JCO.20.02151




ICARE Social Media Post November 2020

Olaparib May Be Cost-Effective Maintenance Treatment For Women With Newly Diagnosed Ovarian Cancer and BRCA Mutation

For further information, view the article available at: https://www.gynecologiconcology-online.net/…/fulltext




ICARE Social Media Post November 2020

ASCO Guideline Updates: Breast Cancer

The American Society of Clinical Oncology (ASCO) published updated guidelines for the management of hereditary breast cancer for the following gene carriers:
 
𝘽𝙍𝘾𝘼1/2
• Consider breast-conserving therapy
• Consider nipple-sparing mastectomy, if medically appropriate
• Advanced breast cancer:
⫸ PARP inhibitors (olaparib, talazoparib) preferred over non-platinum single agent chemotherapy
⫸ Platinum agents are recommended versus taxanes
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• Mastectomy is advised
• Radiation therapy is contraindicated except for those at risk for locoregional recurrence
 
For more information, check out the full article at: https://ascopubs.org/doi/full/10.1200/JCO.20.00299



ICARE Social Media Post November 2020

Clinical Trial Participation Powers Patient’s Positive Attitude

Brooke Thomas has leaned on 12 years of experience as a medical social worker and found ways to stay positive and upbeat through it all – and she has a lot to be positive about these days, thanks to an amazing response to her treatment as part of a clinical trial at Vanderbilt-Ingram Cancer Center. The trial involves PARP inhibitors, a class of drugs with an expanding role in cancer treatment.

http://spr.ly/6186G7Ir8




ICARE Social Media Post October 2020

New ASCO Guidelines On Use Of PARP Inhibitors To Manage Ovarian Cancer

New guidelines for the use of PARP inhibitors to treat ovarian cancer among those with BRCA1 or BRCA2 mutations were published through the American Society of Clinical Oncology (ASCO) to guide providers about the role of this class of drugs in the management of this type of cancer.

Link to the guidelines are available at: https://ascopubs.org/doi/full/10.1200/JCO.20.01924




ICARE Social Media Post October 2020

Addition of Veliparib to Carboplatin/Paclitaxel in Previously Treated Patients With BRCA-Mutated Advanced Breast Cancer

Among 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.

To read the full article visit: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30447-2/fulltext
[This finding was previously outlined last year based on the ESMO 2019’s BROCADE3 abstract; however, the full article was not published until recently]




ICARE Social Media Post September 2020

Rucaparib May Have Antitumor Activity in Male BRCA Carriers with Metastatic Prostate Cancer

For further information, view the article available at: https://ascopubs.org/doi/full/10.1200/JCO.20.01035




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 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

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 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 November 2019

High Frequency of BRCA in Unselected Women with Metastatic Breast Cancer

Did you know? National practice guidelines currently recommend ALL women with metastatic (HER2-) breast cancer to get genetic testing for inherited cancer (including BRCA1/2 testing), because it can guide eligibility for treatment with PARP inhibitors.

A new study led by our colleague at the Vanderbilt-Ingram Cancer Center, Dr. Ben Park, suggests that more women with metastatic breast cancer have BRCA1/2 mutations than previously thought. In fact, of the 100 women with metastatic breast cancer tested through this study, 6% had BRCA1/2 mutations!

Findings from this study highlight the importance of genetic testing for ALL women with metastatic breast cancer to help guide their treatment, AND further guide risk management for themselves and their at-risk family members.

Check out the study at the following link: https://www.ncbi.nlm.nih.gov/pubmed/31465090




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

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

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

The Role of “Non-Truncating” Mutations in RAD51D on Ovarian Cancer Risk

As testing has broadened to include newer inherited cancer genes, studies have suggested that mutations which shorten the protein (“truncating mutations”) in the RAD51D gene are associated with ovarian cancer.  However, a recent study examined ovarian cancer risks for a “non-truncating” change (a single base pair within the gene is changed which is called a missense mutation) in the RAD51D gene. The study was focused on a French-Canadian population in which a specific missense change (c.620C>T) is particularly common.  Findings showed that this change substantially raised the risk for high-grade serous ovarian cancer, which was seen in 3.8% of ovarian cancer patients and 0.2% of controls.  Furthermore, laboratory studies showed that this gene change may confer sensitivity to PARP inhibitors.  This is the first study to confirm a missense mutation in RAD51D and suggests that PARP-inhibitor therapies may be of use among this group of ovarian cancer patients.

Rivera et al. Cancer Res. 2017 Aug 15;77(16):4517-4529. PMID: 28646019.




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

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 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 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 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.