Ursula A. Matulonis, MD
Niraparib (Zejula) demonstrated durable antitumor activity in patients with heavily pretreated homologous recombinant deficiency (HRD)-positive ovarian cancer, according to data from the phase II QUADRA trial.
The PARP inhibitor is currently FDA approved as a maintenance therapy for patients with ovarian cancer, regardless of BRCA
status. The single-arm QUADRA study, results of which were presented at the 2018 ASCO Annual Meeting, is aimed to test the oral agent’s activity in patients with HRD-positive recurrent disease. The primary endpoint was overall response rate (ORR).1
In patients with HRD-positive, platinum-sensitive disease who received ≥3 prior lines of treatment without a PARP inhibitor, the ORR was 27% (14/51). Duration of response (DOR) for this cohort was 9.2 months. The ORR was 29% among patients receiving treatment in the fourth- and fifth-line settings. Toxicity levels were consistent with other niraparib studies and became manageable with dose reductions.
KEYNOTE-100 was another notable study in this setting presented at the 2018 ASCO Annual Meeting. The large, phase II trial indicated that single-agent pembrolizumab (Keytruda) demonstrated significant antitumor activity in patients with PD-L1–positive advanced ovarian cancer. Patients were divided into 2 cohorts based on level of prior treatment and combined positive score (CPS), said lead study author Ursula A. Matulonis, MD.
Data presented suggested that ORR increased with PD-L1 expression. Total ORR for the 376 patients was 8.0%. Across both cohorts, for patients with a CPS ≥1, ORR was 10.2%; for CPS ≥10, it was 17.1%.2
In an interview with OncLive
, Matulonis, chief of the Gynecological Oncology Division at Dana-Farber Cancer Institute and professor of Medicine at Harvard Medical School, highlighted the activity and tolerability of niraparib and discussed other recent data in ovarian cancer.
OncLive: Please provide some background to the QUADRA study.
: The rationale for QUADRA was really to expand the use of the oral PARP inhibitor niraparib into patient populations beyond where it's currently FDA approved. Currently, it is FDA approved for maintenance therapy in women who have responded to platinum-based chemotherapy and have recurrent disease. In order to prolong that maintenance and that remission they have achieved, the FDA granted approval to niraparib as a very broad label. Using niraparib following chemotherapy at a dose of 300 mg—so once somebody's blood counts have come back up to normal—they're ready to go on a PARP inhibitor.
What was the study design?
This is a very large trial looking at single-agent niraparib in more heavily pretreated populations. The total number of participants enrolled was 463, and after a little more than 300 women had been enrolled, an amendment was then issued stating that patients were limited to 3 or 4 prior lines of therapy and they had to have an initial response to chemotherapy. This was to ensure that their disease had some susceptibility to drugs such as PARP inhibitors.
What were the data presented at the 2018 ASCO Annual Meeting?
The full data issued really looked at the primary endpoint, which was ORR in heavily pretreated patients with HRD-positive ovarian cancer. There was a 29% ORR, and this is exciting because these are patients with few options once they get to the fourth-line setting and beyond. Overall, this is a good thing.
Are there any additional data you would like to mention?
Other results being presented are around the germline BRCA
-mutated cohort. This is a subgroup of patients with underlying BRCA
mutations. In that population of heavily pretreated women with 3 or 4 prior lines of therapy, there are excellent response rates. In these women with platinum-sensitive disease, there was a little greater than 40% ORR, which is very impressive. For patients with platinum-resistant cancer, it was still very good at around 25% ORR. Overall for the BRCA
-mutated group, the ORR was close to 30%.
The other telling part of these results is the DOR. For BRCA
-positive patients, it was more than 9 months. For HRD-positive patients, DOR was a little longer than 8 months. In terms of safety, no new safety signals were observed. We did see a necessity for dose reductions from 300 mg to 200 mg, and even sometimes down to 100 mg.