The long-term results of the pivotal SOLO-1 trial have shown that maintenance olaparib more than doubles the 5-year disease-free survival time for patients who have newly diagnosed advanced ovarian cancer with BRCA mutations, according to an update presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 by Susana N. Banerjee, MBBS, PhD, a consultant medical oncologist at The Royal Marsden and reader at The Institute of Cancer Research, London.1
“We are presenting data from the SOLO-1 trial after the longest duration of follow-up for any PARP inhibitor in the newly diagnosed advanced ovarian cancer setting. The benefit derived from maintenance olaparib was sustained substantially beyond the end of treatment. More than half of women in complete response at baseline who received maintenance olaparib for 2 years remained free of relapse 5 years later,” Dr. Banerjee said.
Susana N. Banerjee, MBBS, PhD
In the primary analysis, conducted in May 2018, maintenance olaparib was shown to significantly reduce the risk of disease progression by 70%.2 The current analysis was performed at the March 2020 cutoff, 5 years after the last patient was randomly assigned. At this point, 48.3% of the olaparib group had not experienced disease progression vs 20.5% of the placebo arm. Median disease-free survival was 56.0 months vs 13.8 months, respectively (hazard ratio [HR] = 0.33), Dr. Banerjee reported.
“Previous research of PARP inhibitors in ovarian cancer has only been in patients with relapsed disease, so SOLO-1 has given us the evidence to show that, as a first-line therapy, they can have substantial benefit for patients earlier in the cancer pathway…. These results provide further evidence to support the use of maintenance olaparib as standard of care for women with newly diagnosed advanced ovarian cancer and a BRCA mutation and suggest the possibility of long-term remission (or even cure) for some patients,” she commented.
SOLO-1 was a phase III, randomized, double-blinded, placebo-controlled, multicenter trial evaluating olaparib (300 mg twice daily) as a maintenance monotherapy, compared with placebo, in 391 patients with newly diagnosed BRCA-mutated advanced ovarian cancer who responded to first-line platinum-based chemotherapy. Patients were randomly assigned (2:1) to olaparib or placebo for up to 2 years or until disease progression. Patients who had a partial response at 2 years were permitted to stay on therapy at the physician’s discretion. The median duration of treatment with olaparib was 24.6 months vs 13.9 months with placebo.
The primary endpoint was progression-free survival, the results of which were presented in 2018.2 After the study met its primary endpoint, olaparib was approved for maintenance therapy for advanced ovarian cancer in many countries around the world.
“Patients receiving olaparib had an additional 3.5 years [median, 42.4 months] free of disease progression,” Dr. Banerjee reported. “At 5 years, 48% were progression-free, compared with 21% with placebo.”
Recurrence-free survival was also examined in the subgroup of patients in complete response at baseline. In this group, median recurrence-free survival was not met, and it was 15.3 months with placebo (HR = 0.37). Maintenance olaparib also significantly delayed the second disease progression (progression-free survival 2; HR = 0.46) and the time to subsequent therapy (HR = 0.46) in the overall population, and similarly in patients with complete responses to chemotherapy.
The safety profile of olaparib was consistent with previous observations. Adverse events grade ≥ 3 were seen in 40% of the olaparib arm and 19% of the placebo arm. No additional cases of myelodysplastic syndromes or acute myeloid leukemia were reported; their incidence remained less than 1.5%.
DISCLOSURE: Dr. Banerjee has received honoraria from and served as a consultant or advisor for Amgen, AstraZeneca/MedImmune, Clovis Oncology, GenMab, GlaxoSmithKline, Immunogen, Merck Sereno, Mersana, MSD Oncology, Roche, Seattle Genetics, and Tesaro; has served as an institutional consultant or advisor to Carrick Therapeutics; has received institutional research funding from AstraZeneca, GSK, and Janssen-Cilag; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca and NuCana BioMed.
1. Banerjee S, Moore KN, Colombo N, et al: Maintenance olaparib for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO-1. ESMO Virtual Congress 2020. Abstract 811MO. Presented September 18, 2020.
2. Moore K, Colombo N, Scambia G, et al: Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 379:2495-2505, 2018.
SOLO-1’s invited discussant, Jonathan Ledermann, MD, Professor of Medical Oncology at UCL Cancer Institute and University College London Hospitals, predicted that “an overall survival benefit will occur” with maintenance olaparib, based on the study’s long follow-up and encouraging results from key ...