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ESMO 2018: SOLO-1: Olaparib Maintenance Extends Progression-Free Survival in BRCA1/2-Mutated Advanced Ovarian Cancer

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Key Points

  • “The median PFS for patients who received placebo was only 13.8 months, while the median PFS for those who received olaparib was not reached, but looks to be approximately 3 years longer than the placebo group,” stated Dr. Moore.
  • PFS2 remained significantly improved among patients who had received olaparib maintenance, with a median PFS2 of 41.9 months for placebo vs median not reached for the olaparib group.

Two-year maintenance therapy with olaparib (Lynparza), a poly ADP-ribose polymerase (PARP) inhibitor, led to a substantial improvement in progression-free survival (PFS) in newly diagnosed patients with advanced ovarian cancer and a BRCA1/2 mutation, results from the phase III SOLO-1 trial presented by Moore et al at the European Society for Medical Oncology (ESMO) 2018 Congress show (Abstract LBA7_PR).

“The median PFS for patients who received placebo was only 13.8 months, while the median PFS for those who received olaparib was not reached, but looks to be approximately 3 years longer than the placebo group (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.23–0.41; P < .0001),” reported Kathleen Moore, MD, Associate Professor at the Stephenson Cancer Center, University of Oklahoma.

“While it is too early to say whether we have impacted the fraction of women who could be cured with their front-line therapy, the fact that it is estimated that over 50% of women on the olaparib arm were still progression-free at 4 years as compared to only 11% for placebo speaks to this hope,” she remarked.

“The results of SOLO-1 herald a new era in treatment for women diagnosed with advanced ovarian cancer who carry a BRCA mutation…This study demonstrates an outstanding improvement in PFS over placebo which is maintained even after the olaparib is stopped at 2 years,” added Dr. Moore in a statement.

More About SOLO-1

SOLO-1 is the first double-blind, randomized, prospective phase III trial evaluating frontline olaparib maintenance therapy after platinum-based chemotherapy in newly diagnosed, advanced ovarian cancer (FIGO stage III–IV) with a BRCA mutation. “It provides the first large dataset of prospectively collected outcomes for this population of women,” said Dr. Moore.

A total of 391 patients with high-grade serous or endometrioid ovarian cancer who were in clinical complete or partial response after chemotherapy upon entering the study, were randomly assigned 2:1 to olaparib tablets 300 mg twice per day (n = 260) or placebo (n = 131) for 2 years. The primary endpoint was investigator-assessed PFS from randomization. Secondary outcomes included PFS2, which was time from randomization to second progression; overall survival; and quality of life. Median follow-up was 41 months.

Findings

PFS2 remained significantly improved among patients who had received olaparib maintenance, with a median PFS2 of 41.9 months for placebo vs median not reached for the olaparib group (HR = 0.50; 95% CI = 0.35–0.72; P = .0002).

The most common grade ≥ 3 toxicities with olaparib were anemia (22%) and neutropenia (8%). There was no clinically relevant change in quality of life between groups, and dosing was well tolerated, with only 12% of patients discontinuing olaparib due to toxicity and not disease progression. Furthermore, there was no detriment to quality of life.

Commentary

“These are outstanding results in a worsening disease setting. Not only was olaparib efficacious, but it was also shown to be well tolerated,” said Isabelle Ray-Coquard, MD, PhD, of Université Claude Bernard Lyon Est, Lyon, France, commenting on the results for ESMO. “The findings promise to change practice in this subgroup of patients with a BRCA mutation.”

“Now, two questions remain. Can we expand this benefit to all high-grade serous carcinomas? Looking at existing results in relapse with PARP inhibitor maintenance in all comers, we can anticipate excellent results for all patients with high-grade serous or endometrioid ovarian carcinoma,” said Dr. Ray-Coquard. “Also, what is the best maintenance therapy? Standard first-line therapy in many countries is chemotherapy plus bevacizumab maintenance for the majority of advanced disease, but the question remains whether maintenance with olaparib alone, or in combination with bevacizumab, is preferable. The PAOLA-1 trial will provide some information, and will probably be available next year.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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