Olaparib-Carboplatin Combination Shows Promise for Patients with Ovarian or Triple-Negative Breast Cancer
Philadelphia, PA—The use of the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib (Lynparza), plus carboplatin chemotherapy shows promising activity in patients with recurrent breast or ovarian cancer; furthermore, the order of administration of these therapies did not affect the occurrence of side effects, according to new data from a phase 1 clinical trial presented at the 2015 American Association for Cancer Research (AACR) meeting.
In December 2014, olaparib was approved by the FDA for the treatment of women with ovarian cancer and BRCA mutations.
“Studies to identify treatment combinations that might increase the number of patients benefiting from olaparib are important,” said Victoria L. Chiou, MD, a Medical Oncology Fellow at the National Cancer Institute.
The goal of the study, Dr Chiou noted, was to investigate “the best way to deliver combination therapy using olaparib and carboplatin to maximize DNA damage, which likely correlates with antitumor effects, and minimize clinical toxicities.”
The results, she said, showed that “the overall sequence of treatments did not significantly impact the side effects that patients felt. Moreover, we identified a safe drug treatment schedule that also had preliminary activity, known as tumor shrinkage, in women with breast cancer and ovarian cancer.”
Overall, the women with ovarian cancer and BRCA mutation had a 60% overall response rate (ORR) with the combination of the PARP inhibitor plus chemotherapy, compared with the approximately 30% ORR reported for olaparib alone in heavily pretreated patients with ovarian cancer and BRCA mutation.
Overall, 59 women with recurrent breast or ovarian cancer were included in the study. Of these, 47 women had ovarian cancer, 10 had triple-negative breast cancer, 1 had a uterine carcinosarcoma, and 1 had endometrial cancer. In all, 26 women with ovarian cancer and 4 women with triple-negative breast cancer had a BRCA mutation.
The patients were randomized to 1 of 2 groups; group 1 received olaparib before carboplatin in cycle 1 and carboplatin before olaparib in cycle 2; group 2 received carboplatin before olaparib in cycle 1 and olaparib before carboplatin in cycle 2. Starting with cycle 3, all patients received the same treatment regimen.
Toxicity analysis showed no significant difference in the frequency of grade 3 or 4 adverse events. The most common grade 3 or 4 events were neutropenia and anemia.
Furthermore, updated results showed that olaparib, used for 7 days, plus carboplatin, given once every 21 days, had preliminary clinical activity in heavily pretreated patients with breast or ovarian cancer.
Of the 54 patients in this analysis, 1 woman with triple-negative breast cancer had a complete response lasting 23 months; of the 24 partial responses, 20 were in women with ovarian cancer and 4 were in women with triple-negative breast cancer.
Dr Chiou noted that 2 patients are still on study. “One woman has had a partial response that has persisted more than 19 months, and another woman who had stable disease documented at the initial time of abstract submission has since achieved a partial response and has been on the study for more than 12 months,” she said.