This is a good combination, based on an improvement in response rate, but we need phase III data to see if it really works or not.— Virginia Kaklamani, MD
Moderator of the press conference on this study, Virginia Kaklamani, MD, of the University of Texas Health Science Center at San Antonio, agreed that an improvement in response is important. “If you are a patient with symptoms, such as a cough from lung metastases, and I give you a combination that produces a response and your symptoms go away, your quality of life improves significantly,” she said. “Response rate is extremely clinically meaningful for patients who are symptomatic, which is many of our metastatic patients.”
Dr. Kaklamani said the failure of this randomized phase II trial to meet its primary endpoint “should not deter us from pursuing a potentially interesting medication…. This is a good combination, based on an improvement in response rate, but we need phase III data to see if it really works or not. The U.S. Food and Drug Administration has approved some medications based on response rates, but I would like to see more than an increase in response rate for approval.”
Platinum is a very good therapy in BRCA-mutation carriers, and it’s very hard to go up against it. Maybe patients are already getting a good benefit from platinum, and veliparib isn’t further boosting that.— Melinda L. Telli, MD
Associate Professor of Medicine at Stanford University Medical Center, Palo Alto, California, told The ASCO Post that the lack of a real benefit for the addition of veliparib is presumably due to the potency of the carboplatin backbone against BRCA-mutated tumors.
“Platinum is a very good therapy in BRCA-mutation carriers, and it’s very hard to go up against it,” she said. “Maybe patients are already getting a good benefit from platinum, and veliparib isn’t further boosting that.” Veliparib may have a better role as a means of potentiating the effect of chemotherapy, suggested Dr. Telli, since it is not a particularly potent single agent.
This study differs from phase III trials ongoing with other poly (ADP-ribose) polymerase (PARP) inhibitors, which are not head-to-head comparisons with a platinum. “All the other companies are not taking that risk,” she said. “They are playing it safe, taking a different approach by comparing these more potent single-agent drugs to physician’s choice of chemotherapy that does not include a platinum. You could ask the question of whether had the company designed this trial differently, the result would have been different.”
Dr. Telli added that a study of veliparib, carboplatin, and paclitaxel in early triple-negative breast cancer (with or without BRCA mutations) will be informative. “It may be that in the population without BRCA mutations, adding a PARP inhibitor may help sensitive tumors to platinum. Maybe we will see something quite different there,” she added. ■
Disclosure: Dr. Kaklamani has received research support from Myriad and AbbVie. Dr. Telli reported no potential conflicts of interest.
The trial did not meet the primary endpoint, but we think the trend toward improved progression-free survival and overall survival is encouraging.— Hyo Sook Han, MD
A randomized phase II study in women with metastatic breast cancer who have mutations in BRCA1 or BRCA2...!-->!-->