Updated OS Results Add Evidence On Olaparib Maintenance For Recurrent Serous Ovarian Cancer

Patients with recurrent, platinum-sensitive serous ovarian cancer may derive a survival benefit from olaparib after chemotherapy

medwireNews: Updated analysis from Study 19 suggests that olaparib maintenance monotherapy after platinum-based chemotherapy might extend overall survival (OS) in patients with platinum-sensitive, recurrent serous ovarian cancer, especially those with BRCA1/2 mutations (BRCAm).

“[T]his is the first analysis to show survival data in patients with recurrent BRCA mutated ovarian cancer that are consistent with previously reported benefits in progression-free survival and time to first and second subsequent therapy or death”, write Jonathan Ledermann, from UCL Cancer Institute in London, UK, and co-workers.

“Taken together, the available data support the long-term benefit and tolerability of maintenance olaparib in patients with BRCAm and platinum-sensitive recurrent serous ovarian cancer”, they say in The Lancet Oncology.

This third analysis of the secondary endpoint of OS, at a point of “high data maturity”, gave a median OS of 29.8 months for the 136 patients who were randomly assigned to receive olaparib 400 mg twice daily versus 27.8 months for the 129 patients who were given placebo.

The researchers say that the hazard ratio (HR) of 0.73 had a nominal p value of 0.025 which did not meet the threshold of significance of 0.0095, but explain that as the study was not powered to show a significant benefit in OS, the analysis should be considered “descriptive” only.

And they believe that the trend to improved OS with olaparib was driven by its effects in a subgroup of 136 patients with BRCAm, who had a median OS of 34.9 months with olaparib versus 30.2 months with placebo, giving a HR of 0.62 with a nominal p value of 0.025.

In all, 15% of 74 BRCAm patients received the drug for 5 years or longer, “highlighting that this PARP inhibitor can significantly change the disease course”, the team writes.

For the patients with wild-type BRCA1/2, OS was a median of 24.5 months and 26.6 months for the olaparib and placebo groups, respectively, with a HR of 0.83 and a nominal p value of 0.37.

But the researchers note that “some separation is seen at the tail end of the BRCA[wild type] survival curves for the two treatment groups, suggesting that a further subset of patients might exist who receive benefit from olaparib treatment”.

Further research into alternative means of homologous recombination repair deficiency, such as mutations or epigenetic mechanisms, which might result in olaparib benefit among women wild-type for BRCA1/2 are now being examined, they say.

The authors note that study achieved “[c]linically useful long-term exposure to olaparib” with “no new safety signals”.

Among 32 patients who received olaparib for at least 2 years, 94% had one or more adverse events and 47% had at least one grade 3 or more severe event, with rates of the most common side effects comparable to those in earlier reports. These included low-grade nausea (75 vs 40% of five placebo-treated controls), fatigue (56 vs 40%), vomiting (38 vs 0%) and anaemia (25 vs 20%).

The most common grade 3 and more severe events in both treatment groups were fatigue (8 vs 3%) and anaemia (6 vs 1%) and serious events were recorded in 22% and 9% of patients, respectively.

Reference

Ledermann JA, Harter P, Gourley C, et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol 2016; Advance online publication 8 September. DOI: http://dx.doi.org/10.1016/S1470-2045(16)30376-X

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