Dr. Rivkin and I attended the annual meeting of the American Society of Clinical Oncology (ASCO)—a gathering of 38,000 oncology experts from all over the world—in early June in Chicago, Illinois. In addition to oncologists, the attendees included researchers, educators, advocates, research funders, survivors and representatives from genetic testing, drug and other services companies. Our aims of attending ASCO were to learn about the latest findings in the prevention, early detection and treatment of ovarian cancer, meet with ovarian cancer researchers, and to meet with leaders from organizations focused on ovarian cancer research, education and advocacy from around the world. This year there were developments in two hot areas pertinent to ovarian cancer that were at the center of discussion at ASCO: PARP inhibitors and surgical treatment of ovarian cancer (see below for highlights). We left ASCO optimistic and inspired—both from learning about new scientific advances and about opportunities for collaboration with other ovarian cancer focused organizations. We have a lot of work to do and we’re determined to do it!
Here are the highlights of ovarian cancer science and discussions from ASCO:
PARP Inhibitor Highlights
Our cells have a large array of proteins that are mobilized to detect and correct damage that can occur on DNA to prevent mutations and cancer. PARP inhibitors are effective for the treatment of tumors that have defects in proteins needed for response to DNA damage. BRCA1, BRCA2 and many other ovarian and breast cancer genes are components of the cell’s DNA damage response program. Tumors in women with BRCA and other gene mutations have a defective DNA damage response; therefore, PARP inhibitors have been effective in treatment for those women. Some PARP inhibitors are approved for treatment of women who have had several other therapies prior to their use. Other PARP inhibitors are approved for maintenance, meaning that women who have finished treatment take the PARP inhibitor to delay recurrence. A key challenge to PARP inhibitor effectiveness is that even in women who do respond, the duration of the response is limited and the tumor comes back. There was a lot of discussion at ASCO of what combination therapies can be used to increase PARP inhibitor response, initially to increase time before recurrence but, of course, with the goal of eliminating the cancer completely.
- Status of approval of different PARP inhibitors in the US by the FDA and in Europe by the EMA:
- Maintenance Therapy: Niraparib is approved by the FDA for maintenance therapy for all patients regardless of histology, BRCA & DNA damage response status. Olaparib approval for maintenance therapy is awaited in US. Olaparib is approved in Europe for maintenance therapy for BRCA mutation carriers only. Niraparib approval is awaited in Europe
- Treatment: Rucaparib and Olaparib are approved by the FDA as therapy for women with BRCA mutations who’ve received several rounds of other chemotherapy.
- The quality of life on olaparib is no different than on placebo for patients with ovarian cancer
- Testing of tumors for DNA damage repair status may be key to identifying more patients who can benefit from PARP inhibitor therapy, including those who do not carry BRCA mutations
- There is a need to identify new biomarkers to identify tumors that have defective DNA repair to extend use of PARP inhibitors. Genomic scarring and other tests currently used to identify DNA repair defective tumors may not be able to tell if certain chemoresistance mechanisms may be at play which would prevent PARP inhibitor.
- There was significant discussion on identifying components of the DNA damage repair and response pathways as targets for combination therapy with PARP inhibitors. Currently at least ten targets (ATR, ATM, WEE1, etc) with known inhibitors exist and await results for testing in combination with PARP inhibitors.
- There was also discussion of targeting the environment of the tumor to increase efficacy of PARP inhibitors. One example is to create hypoxic (low in oxygen) local environment which been shown to decrease DNA damage response.
Surgery related developments
Surgery remains an important component of ovarian cancer treatment. Here are reports of some studies that examine different surgery related practices.
- The LION trial finds that removing lymph nodes during cancer surgery in women who do not have cancer positive lymph nodes does more harm than good.
- The DESKTOP III trial shows that women with platinum sensitive cancer who have surgery (with no residual disease), after first recurrence, before chemo have better outcomes without increasing adverse events
- We need to refine the way we classify ovarian cancer to better define treatments and prognosis.
- Patient engagement improves survival: Patients with advanced cancer who used an online tool to report side effects & symptoms lived 5 months longer than those who did not and also had reduced ER visits.
- Discussion on testing of germline (inherited) and somatic (non-inherited, usually from the tumor) mutations and different practices of genetics clinics, including a focus on testing non-BRCA genes
You can follow the conversations we had as ASCO with #ASCOvarian.