|The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Intensive maintenance therapy with the PARP inhibitor olaparib added to bevacizumab resulted in a significant and clinically meaningful improvement in progression-free survival in patients with advanced ovarian cancer, according to the results of the phase 3 PAOLA-1/ENGOT-ov25 study presented at the European Society for Medical Oncology (ESMO) Congress 2019.1
The study enrolled 537 all-comers with newly diagnosed disease who had been treated with platinum-based chemotherapy plus bevacizumab. Patients were randomly assigned in a 2:1 ration to receive to olaparib tablets plus bevacizumab or placebo plus bevacizumab.
With a median follow-up of 2 years, the investigator-assessed progression-free survival was 22.1 months for the olaparib arm compared with 16.6 months for placebo (hazard ratio [HR], 0.59; 95% CI, 0.49-0.72; P <.0001).
“This study reports the greatest hazard ratio (0.59) and longest progression-free survival we have ever seen,” study author Isabelle Ray-Coquard, MD, PhD, Centre Leon Bérard, Université Claude Bernard, Lyon, and president of the GINECO group France, said in a press release.2 “Patient selection was not restricted by surgical outcome or BRCA mutation status, so participants represent the general population of women with advanced ovarian cancer. Previous studies of relapse have suggested benefits from combining anti-angiogenic agents and PARP inhibitors and today’s results appear to support this.”
Looking at those subgroups, patients with BRCA mutations assigned to olaparib had a median progression-free survival of 37.2 months compared with 21.7 months for placebo (HR=0.31; 95% CI, 0.20-0.47). Among patients with homologous recombination deficiency (HRD) the median progression-free survival was also 37.2 months for olaparib compared with 17.7 months for placebo (HR=0.33; 95% CI, 0.25-0.45).
Grade 3 or worse adverse events were observed in 57% of patients assigned olaparib and 51% assigned placebo. The most common of these adverse events were hypertension and anemia. Five treatment-emergent adverse events of death occurred; one in the olaparib arm and four in the placebo arm.
In regard to the data’s relevance, Dr Ana Oaknin, Vall d’Hebrón Institut d’Oncologia (VHIO), Barcelona, said: “The main goal in ovarian cancer is to avoid relapse after first-line therapy because otherwise the probability of cure is quite low. The combination of bevacizumab and olaparib as maintenance therapy should become a new standard of care for patients with advanced ovarian cancer. The PAOLA-1/ENGOT-ov25 trial did not include patients with no response to first-line chemotherapy, but this is a small group. This trial is a significant step forward in treatment for these women.”
Disclosure: The study was funded by Merck Sharp & Dohme Corp. For a full list of author disclosures, please refer to the original abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.
- Ray-Coguard IL, Pautier P, Pignata S, et al. Phase III PAOLA-1/ENGOT -ov25trial: 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. Presented at: European Society of Medical Oncology (ESMO) Congress 2019; September 27-October 1, 2019: Barcelona, Spain. Abstract LBA2_PR.
- European Society of Medical Oncology (ESMO). Ovarian cancer: more women benefit from maintenance combined targeted therapy. Published September 28, 2019.