The following article features coverage from the Society of Gynecologic Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Results of subgroups analyses of patients enrolled in a phase 3 study evaluating bevacizumab-based maintenance therapy with addition of either the PARP inhibitor olaparib or placebo following first-line platinum-based chemotherapy plus bevacizumab showed that patients were more likely to benefit from the former approach if they underwent upfront compared with interval cytoreductive surgery. These findings were accepted for presentation at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and released on March 28, 2020.1

In the placebo-controlled, double-blind, multinational PAOLA-1/ENGOT-ov25 study patients with previously untreated stage III/IV ovarian/fallopian tube/peritoneal cancer characterized by high-grade serous or endometrioid histology who had achieved a complete or partial response following first-line platinum-based chemotherapy plus bevacizumab were randomly assigned in a 2:1 ratio and stratified by tumor BRCA mutation status to receive maintenance therapy with olaparib plus bevacizumab (537 individuals) or placebo plus bevacizumab (269 individuals).  The primary study endpoint was investigator-assessed progression-free survival (PFS).1,2

Previously reported results for this study evaluated at a median follow-up of 2 years or longer, revealed PFS was significantly increased for the  patients receiving olaparib-containing maintenance therapy, with median PFS of 22.1 months vs 16.6 months for those receiving maintenance therapy with and without olaparib (hazard ratio [HR], 0.59; 95% CI, 0.49-0.72; P <.0001). Furthermore, more pronounced differences between study arms in favor of olaparib-containing maintenance therapy were observed in subgroups of patients with disease characterized by a deleterious tumor BRCA mutation or homologous recombination deficiency.2

The analysis presented here, which was undertaken at a median follow-up of 22.9 months, extends these results to include assessments of the efficacy of maintenance therapy with olaparib plus bevacizumab according to timing of surgery, whether or not residual tumor was present following surgery, and stage of disease.1


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While upfront cytoreductive surgery was performed in 51% of patients, 42% of patients were classified as having had interval cytoreductive surgery, which is surgery performed following a few cycles of chemotherapy, and 7% of patients did not undergo surgery, Although a PFS benefit was observed for addition of olaparib to bevacizumab-based maintenance therapy in patients undergoing upfront surgery alone or interval surgery, the impact appeared to be more pronounced in those patients treated with the former surgical approach.

Specifically, for the subgroup of patients treated with upfront surgery, median PFS was 29.6 months for the olaparib-containing arm and 18.2 months for the control arm (HR, 0.52; 95% CI, 0.40-0.69), and 21.4 months and 16.7 months for these respective arms for those treated with interval surgery (HR, 0.66; 95% CI, 0.50-0.87).

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Similar findings were observed with respect to the presence of macroscopically detectable residual tumor, with those patients without detectable residual tumor showing a more pronounced PFS benefit with addition of olaparib to maintenance therapy with bevacizumab.

Furthermore, for the 245 patients who underwent upfront surgery and had undetectable residual disease, median PFS was 39.3 months for patients treated with olaparib plus bevacizumab maintenance therapy compared with 22.1 months for those receiving maintenance therapy with placebo plus bevacizumab (HR, 0.47; 95% CI, 0.21-0.75). 

Finally, for the 211 patients with stage III disease who underwent upfront surgery and were without detectable residual disease, median PFS was not reached in the olaparib-containing arm and was 24.9 months in the control arm (HR, 0.45; 95% CI, 0.27-0.75).

Disclosures: Two study authors disclosed financial relationships with Roche and AstraZeneca. For a full list of disclosures, please refer to the study abstract.

Read more of Cancer Therapy Advisor‘s coverage of SGO 2020 by visiting the conference page.

References

  1. Grimm C, Cropet C, Ray-Coquard I. Maintenance olaparib plus bevacizumab (bev) after platinum-based chemotherapy plus bev in patients (pts) with newly diagnose. d advanced high-grade ovarian cancer (HGOC): Efficacy by timing of surgery and residual tumor status in the Phase III PAOLA-1 trial. Submitted to: Society of Gynecologic Oncology (SGO) 2020 Annual Meeting on Women’s Cancer. Abstract 34.
  2. Ray-Coquard IL, Pautier P, Pignata S, et al. Phase III PAOLA-1/ENGOT-ov25 trial: Olaparib plus bevacizumab (bev) as maintenance therapy in patients (pts) with newly diagnosed, advanced ovarian cancer (OC) treated with platinum-based chemotherapy (PCh) plus bev. Ann Oncol. 2019;30 (Suppl_5): ix191-ix192. Abstract LBA2_PR.