Combination yields ‘promising’ results for recurrent, BRCA–deficient ovarian cancer
Researchers at University of New Mexico Comprehensive Cancer Center are evaluating a novel treatment combination for women with recurrent ovarian cancer who have BRCA1 or BRCA2 gene mutations.
The phase 1 portion of the trial verified the safety of olaparib (Lynparza, AstraZeneca) — a PARP inhibitor that may exploit tumor DNA damage response pathway deficiencies to kill cancer cells — and tremelimumab, a CTLA-4 monoclonal antibody.
Enrollment for the phase 2 portion of the trial opened in May 2016.
Sarah F. Adams, MD, associate professor in the division of gynecologic oncology at University of New Mexico Comprehensive Cancer Center, spoke with HemOnc Today about the trial and why she thinks the combination approach will help improve outcomes in this patient population.
Question: Can you describe the rationale for this study?
Answer: The trial is based upon data we developed in our lab that initially tested the hypothesis that PARP inhibitors may sensitize BRCA–deficient ovarian cancer to immunotherapy, specifically immune checkpoint inhibitors. We have data — and other people also have produced data — that suggest BRCA–deficient ovarian cancer may be more visible to the immune system than BRCA wild-type ovarian cancers. In our lab, we showed that treating BRCA–deficient tumor cells with a PARP inhibitor further enhanced their immunogenicity, or their ability to be recognized and killed by T cells.
Q: Why do you think the combination approach may help improve outcomes?
A: We think that, if we combine this treatment with a PARP inhibitor, we can enhance tumor clearance and hopefully generate long-term results in patients. We have shown this in mouse models in the lab, and this trial is an opportunity to translate data to be able to benefit patients who are being treated at University of New Mexico.
Q: What have you found so far?
A: We have observed promising results in some patients, which generated a lot of enthusiasm for us. However, it is too early to draw conclusions because we have not yet met our enrollment goals. We have submitted an embargoed abstract for the upcoming ASCO Annual Meeting.
Q: What do you hope you will find next?
A: My hope is that we will find that the combination therapy not only reduces tumor burden, but also prolongs response compared with either drug alone. This is what we found with mouse models. The beauty of immunotherapy is that it can generate an immune response against the tumor, and it has the potential to create a memory response so that a person’s body rejects tumor recurrence.
Q: Once this trial is complete, what will future research entail?
A: This trial is designed to evaluate the response rate to this combination. We would like to expand the trial to evaluate the potential of this regimen to achieve long-term responses. Another area we are interested in expanding is to see whether the combination is effective for a larger cohort of women, because our trial is limited to women with BRCA mutations.
Q: Is there anything else that you would like to mention?
A: The eligibility requirements for this trial are broad. There are no restrictions on the number of prior chemotherapy regimens a woman may have had before enrolling in this trial, and women who were previously treated with a PARP inhibitor also are eligible. All eligible patients who want to learn more about this trial may call University of New Mexico Comprehensive Cancer Center at (505) 272-4946 and ask for Sheri Westgate, RN, the nurse who is running the trial. – by Jennifer Southall
For more information:
Sarah F. Adams, MD, can be reached at email@example.com.
Disclosure: The study is supported by the New Mexico Cancer Care Alliance and AstraZeneca. Adams reports no relevant financial disclosures.