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Updates in Research on Treating Hereditary Cancers

May 19, 2016

Note: This post which was originally published 08/4/15 was just updated on 05/19/16.

In December 2014, the FDA approved the first targeted therapy for people with BRCA mutations. Lynparza, a type of medication known as a PARP inhibitor, was approved for women with a BRCA mutation to treat advanced ovarian, fallopian tube, or primary peritoneal cancer that has progressed after three or more rounds of chemotherapy treatments. Lynparza’s FDA approval extends only to certain women with ovarian cancer; however, a desperate need exists for more therapies to treat other cancers associated with hereditary breast and ovarian cancer (HBOC). Scientists are researching PARP inhibitors and other agents for the following situations:

  • Cancers other than ovarian; including breast, pancreatic, and prostate cancers
  • Cancers caused by other gene mutations, such as PALB2, PTEN, ATM and others
  • Earlier stage cancers
  • Cancers that have not responded to, or have progressed after PARP inhibitors

Until now, PARP inhibitor studies have focused almost exclusively on people with advanced cancer. At our last Joining FORCEs conference, Alan Ashworth, PhD, one of the researchers who developed PARP inhibitors, discussed how the largest potential benefit of PARP inhibitors will come from using them in earlier-stage cancers because early stage cancers are less likely to develop resistance to treatment. Clinical research on early stage cancers only occur once the safety and activity of a drug has been established. PARP inhibitors have reached this milestone in their development.

Fortunately, clinical trials looking at treatments for different types of HBOC-related cancers are open and enrolling patients. This includes studies for people with:

Earlier stage cancers:

  • OlympiA is a clinical trial for people with a BRCA1 or BRCA2 mutation who have breast cancer that has not advanced to stage 4; people who have been recently diagnosed with stage 2 or stage 3 breast cancer may be eligible. The study is evaluating whether adding the PARP inhibitor olaparib after adjuvant or neoadjuvant treatment is safe and improves outcomes.
  • INFORM is a study for newly-diagnosed breast cancer patients who who have a BRCA1 or BRCA2 mutation. The study is evaluating whether the chemotherapy drug cisplatin is better than currently used standard chemotherapy drugs (Cyclophosphamide/Doxorubicin).

Cancers other than ovarian:

Several studies are open for other types of cancer associated with HBOC.

Mutations in other genes associated with HBOC:

Cancers associated with HBOC regardless of mutation status:

  • ARIEL2 is a phase 2 PARP inhibitor trial for women with relapsed, high-grade serous or endometrioid ovarian cancer. ARIEL2 is now enrolling its expansion phase to include patients who have progressed after three lines of prior chemotherapy and are platinum sensitive or platinum resistant.  All patients enrolled in the study will receive the PARP inhibitor rucaparib.
  • Quadra is a study for women with advanced, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received at least 3 previous chemotherapy regimens (which may have included a PARP inhibitor).

Cancers that did not respond or progressed after PARP inhibitors:

Several studies are open to patients whose cancers did not respond or recurred after treatment with a PARP inhibitor, this is good news that will hopefully yield more treatment options for people with HBOC-associated cancers.

All of these clinical trials need to be completed so that as many people as possible may benefit from these new therapies. That is why we are turning to the community and health care providers to help to spread the word about clinical trials for HBOC-related cancers. To search for prevention, detection, treatment and quality of life research studies enrolling people with HBOC, visit our HBOC Research Search Tool. We will have further updates on some of these studies and agents after the American Society of Clinical Oncology’s Annual Conference, so stay tuned.

 

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One Comment

  1. […] PARP inhibitors are in development, and clinical trials are open and enrolling patients with, and without BRCA mutations. The FDA approved olaparib in December 2014 to treat women with advanced ovarian cancer with […]

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