Paul A. DiSilvestro, MD
Isabelle Ray-Coquard, MD, PhD
First-line maintenance therapy with olaparib extended survival beyond historical expectations in some women with newly diagnosed advanced ovarian cancer, according to long-term follow-up of two phase III studies presented at the European Society for Medical Oncology (ESMO) Congress 2022.1,2 Paul A. DiSilvestro, MD, of Women and Infants Hospital, Providence, Rhode Island, presented the results from the SOLO-1 trial,1 and Isabelle Ray-Coquard, MD, PhD, of Centre Léon Bérard, Lyon, France, and President of the GINECO group, presented the results from the PAOLA-1 trial.2
In the SOLO-1 trial, more than two-thirds of patients with advanced BRCA-mutated ovarian treated with olaparib maintenance therapy cancer were alive at 7 years compared with 46% of those randomly assigned to receive placebo, translating to a 45% reduction in death. The study set the statistical significance bar at a P value less than .0001, and survival results achieved a P value of .0004. Results from SOLO-1 were published in the Journal of Clinical Oncology to coincide with Dr. DiSilvestro’s presentation.3
“These 7-year results provide further confirmation that the benefit of maintenance olaparib extends well beyond its 2-year treatment cap,” said Dr. DiSilvestro. “These results support the use of maintenance olaparib to achieve long-term remission in women with newly diagnosed advanced ovarian cancer and a BRCA mutation.”
In the PAOLA-1 trial, no significant benefit in overall survival was observed in women with newly diagnosed advanced ovarian cancer with the addition of olaparib to bevacizumab maintenance therapy in the overall population.2 However, a meaningful improvement in overall survival was observed in the homologous recombination deficiency (HRD)-positive subgroup. In this subgroup, the 5-year overall survival rate was 65.5% with the addition of olaparib vs 48.4% with bevacizumab maintenance alone, “representing a 38% improvement.
“These data confirm the addition of olaparib to bevacizumab as a standard of care for HRD-positive patients in this setting [following response to first-line chemotherapy] and the importance of precision medicine and biomarker testing to guide treatment decisions,” said Dr. Ray-Coquard.
SOLO-1 was a double-blind phase III trial that included 391 women with newly diagnosed, advanced BRCA-mutant ovarian cancer. Platinum-responsive participants were randomly assigned 2:1 to maintenance therapy with olaparib or placebo for up to 2 years. The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo. Median follow-up exceeded 87 months in both study arms.
Median time from randomization to first subsequent therapy or death served as a surrogate for progression-free survival. Median progression-free survival was 64 months with olaparib vs 15.1 months with placebo, representing a 63% improvement with olaparib. At data cutoff, 45.3% of women in the olaparib arm had not been treated with a subsequent therapy, compared with 20.6% of women in the placebo arm.
Time to the second subsequent therapy also favored maintenance therapy with olaparib over placebo: median 93.2 months vs 40.7 months. “This indicates a continued benefit [for olaparib] after the first subsequent therapy,” Dr. DiSilvestro observed.
No new safety signals for olaparib emerged during the study. One new case of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was reported in the olaparib group since the primary data cutoff 4 years ago, for a total of four cases at 7 years with olaparib vs one case with the placebo. New primary malignancies (most commonly breast cancer) were well balanced between the two arms.
A total of 38.1% of events have occurred thus far, and the final survival analysis will be conducted when 60% of events have occurred. “It may be many years before we reach that final analysis,” Dr. DiSilvestro said.
The phase III PAOLA-1 study assigned 537 patients with newly diagnosed ovarian cancer to receive olaparib plus bevacizumab, and 269 were assigned to receive placebo plus bevacizumab.
Median follow-up was 62 months. Median overall survival in the intent-to-treat population did not significantly differ in the two study arms: 5 months with olaparib plus bevacizumab vs 51.6 months with placebo. The 5-year overall survival rate was 47.3% vs 41.5%, respectively. The 5-year overall survival rates were much better with olaparib plus bevacizumab in the subset of patients with a BRCA mutation: 73.2% with olaparib plus bevacizumab and 53.8% with placebo, a 40% improvement associated with the addition of olaparib.
For new data on the use of olaparib in ovarian cancer from the SOLO-1 trial, see an interview with Paul A. DiSilvestro, MD, on The ASCO Post Newsreels at ascopost.com/videos.
In an exploratory analysis of HRD-positive patients that excluded the BRCA-positive patients, the 5-year overall survival rates were 54.7% with olaparib plus bevacizumab vs 44.2% with placebo, an improvement of 29%. No benefit of maintenance olaparib plus bevacizumab was observed in the HRD-negative subgroup of patients.
Median progression-free survival was 46.8 months with olaparib plus bevacizumab vs 17.6 months with bevacizumab plus placebo. The 5-year progression-free survival rate was 46.1% vs 19.2%, respectively.
No new safety signals were observed. Adverse events of special interest with olaparib in combination with bevacizumab vs bevacizumab alone included MDS/AML/aplastic anemia, new primary malignancies, and pneumonitis/interstitial lung disease/bronchiolitis.
DISCLOSURE: Dr. DiSilvestro has served on advisory boards for AstraZeneca and GSK/Tesaro. Dr. Ray-Coquard reported financial relationships with AbbVie, Agenus, Advaxis, Bristol Myers Squibb, PharmaMax, GenMab, AstraZeneca, Pfizer, Roche, GlaxoSmithKline, MSD, Deciphera, Mersena, Merck Serono, Novartis, Amgen, Tesaro, and Clovis.
1. DiSilvestro P, Banerjee S, Colombo N, et al: Overall survival at 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation who received maintenance olaparib in the SOLO1/GOG-3004 trial. ESMO Congress 2022. Abstract 517O. Presented September 9, 2022.
2. Ray-Coquard I, Leary A, Pignata S, et al: Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola)plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC). ESMO Congress 2022. Abstract LBA29. Presented September 9, 2022.
3. DiSilvestro P, Banerjee S, Colombo N, et al: Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: The SOLO1/GOG 3004 trial. J Clin Oncol. September 9, 2022 (early release online).
Jonathan Ledermann, MD
Formal discussant Jonathan Ledermann, MD, of UCL Cancer Institute University College London, commented on both phase III trials. He was enthusiastic about the SOLO-1 results: “Perhaps, we really are seeing a cure in some of these patients.” He noted that overall...