Olaparib associated with non-BRCA–mutated ovarian tumor shrinkage

Gelmon KA. Lancet. 2011;doi:10.1016/S1470-2045(11)70214-5.

Nearly one in four women diagnosed with ovarian cancer without BRCA mutations experienced tumor shrinkage while assigned to the PARP inhibitor olaparib, according to results from a phase 2, multicenter, open-label, non-randomized study.

Women with breast cancer did not respond to olaparib, regardless of BRCA mutation status.

From July 8, 2008 to Sept. 24, 2009, 64 women with ovarian cancer and 26 with breast cancer were treated with 400 mg twice daily olaparib (AstraZeneca). Among patients with ovarian cancer, 17 had the BRCA mutation — 13 with BRCA1 or BRCA2 mutations — and 47 did not.

Sixty-three patients in the ovarian cancer group had target lesions and were evaluable for response. Overall, 18 patients responded to the drug (ORR=29%; 95% CI, 19%-41%). All responses were partial responses. Response was 41% in patients who carried the mutation and 24% for those negative for the mutation.

The best median percent change in target-tumor baseline size was 14.2% reduction. Median PFS was 192 days in patients who did not carry the mutation, 221 for those with the mutation and 219 days for the entire cohort.

All patients had at least one adverse event and 88% of those were associated with olaparib. Adverse events observed in at least 20% of patients included fatigue, nausea, vomiting, decreased appetite and abdominal distension.

Twenty-three patients (36%) had grade-3/grade-4 adverse events, 16% of which were caused by olaparib. Two patients discontinued the study due to toxicities associated with olaparib.

Follow HemOncToday.com on Twitter.