Joining FORCES is the FORCE newsletter with news, views and supportive information for individuals concerned about hereditary breast and ovarian cancer.
by Sue Friedman
PARP inhibitors (PARPis) are experimental medications that were found in early studies to be specifically effective against BRCA-related cancers. These drugs block an enzyme used by cells to mend breaks in DNA. Cancer cells in people with BRCA mutations have problems repairing DNA already, and the PARPis make that worse. Theoretically, these drugs should spare healthy cells that have at least one working copy of the BRCA gene, with limited side effects or toxicity. Because they are not yet FDA-approved, PARPis are not available outside clinical trials, but several such trials are currently recruiting participants.
Early PARPi research generated a lot of excitement. In the first trials, the drugs effectively treated some people with BRCA mutations and advanced cancers, including those who have already undergone multiple prior treatments with standard chemotherapy drugs. Not all patients benefitted, but enough did to warrant larger trials. Overall, PARPis were well tolerated, although some patients developed fatigue, nausea, anemia, and low platelet counts. After early successes, trials that expanded to include more people without BRCA mutations were less successful and received quite a bit of negative attention. But closer inspection revealed several reasons why these later studies may have been less successful. These insights (shown below) provide hope that researching these agents remains worthwhile.
Despite these setbacks, PARPi research continues and is now focused on the population for which these drugs were initially developed: people with BRCA mutations. If these studies are successful, PARPi research could expand to earlier-stage cancers or prevention. Ongoing investigations of PARPis include:
The participation of the HBOC community in PARPi research is critical. If enrollment falls short, scientists and pharmaceutical companies may decide that the HBOC community is too difficult to research, and fewer studies will be designed. If you are interested in participating, ask your oncologist about studies in your area. Prior treatment sometimes affects participation eligibility; if you are newly diagnosed with a primary or recurring cancer, consider enrolling in a PARP inhibitor trial as early after diagnosis as possible. Share this information with friends and relatives. Review the FORCE and clinicaltrials.gov websites for finding PARP inhibitor studies.
Ledermann J, et. al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. Volume 366:15 (2012): 1382-1392.
Kaye SB, et. al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J. Clin. Oncol. Volume 30:4 (2012): 372-379.
Gelmon KA, et. al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncology. Volume 12:9 (2011): 852-861.
Patel AG, et. al. Failure of iniparib to inhibit poly(ADP-Ribose) polymerase in vitro. Clin. Cancer Res. Volume 18:6 (2012): 1655-1662.