In an analysis of health-related quality of life and patient-centered outcomes in the phase III SOLO-1 trial reported in The Lancet Oncology, Friedlander et al found no clinically meaningful difference in health-related quality of life—and improved quality-adjusted progression-free survival and time without significant symptoms of toxicity—among patients with newly diagnosed advanced BRCA-mutant ovarian cancer who received maintenance olaparib vs placebo.
The trial showed that maintenance olaparib was associated with a significant progression-free survival benefit vs placebo in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in response after platinum-based chemotherapy.
The substantial progression-free survival benefit provided by maintenance olaparib in the newly diagnosed setting was achieved with no detrimental effect on patients’ [health-related quality of life] and was supported by clinically meaningful quality-adjusted progression-free survival and [time without significant symptoms of toxicity] benefits with maintenance olaparib vs placebo.— Friedlander et al
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Study Details
In the double-blind trial, 391 patients were randomly assigned 2:1 to receive olaparib at 300 mg twice daily (n = 260) or placebo (n = 131). The secondary endpoint of health-related quality of life was assessed as change from baseline in the Functional Assessment of Cancer Therapy-Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months among all randomly assigned patients; TOI scores range from 0 to 100 (higher score = better health-related quality of life), with a clinically meaningful difference defined as a within- or between-group difference of ≥ 10 points. Prespecified exploratory analyses included evaluation of quality-adjusted progression-free survival and time without significant symptoms of toxicity. Quality-adjusted progression-free survival is a measure incorporating duration of good health-related quality of life and progression-free survival derived from the product of the EuroQoL EQ-5D-5L single-index utility score from random assignment to disease progression and restricted mean progression-free survival. Time without significant symptoms of toxicity was derived from restricted mean progression-free survival minus time with toxicity, with toxicity defined as grade ≥ 2 nausea, vomiting, or fatigue (most common symptoms associated with olaparib).
Health-Related Quality of Life and Patient-Centered Outcomes
Median follow-up was 40.7 months (interquartile range [IQR] = 34.9–42.9 months) in the olaparib group and 41.2 months (IQR = 32.2–41.6 months) in the placebo group.
At 24 months, there were no clinically meaningful changes in TOI from baseline within the olaparib group (adjusted mean change = 0.30 points, 95% CI = −0.72 to 1.32 points) or within the placebo group (adjusted mean change = 3.30 points, 95% CI = 1.84–4.76 points). The between-group difference of −3.00 points (95% CI = −4.78 to −1.22 points, P = .0010) did not meet the criterion for a clinically meaningful change.
At primary analysis, median progression-free survival was not reached in the olaparib group vs 13.8 months in the placebo group. Restricted mean progression-free survival was 36.39 months vs 21.46 months (difference = 14.93 months, P < .0001). Mean EQ-5D-5L single-index utility score was 0.817 vs 0.819 (difference = –0.002, P = .84). Mean duration of toxicity was 3.24 months vs 1.22 months (difference = 2.02 months, P = .004).
Mean quality-adjusted progression-free survival was 29.75 months (95% CI = 28.20–31.63 months) in the olaparib group vs 17.58 months (95% CI = 15.05–20.18 months) in the placebo group. The between-group difference was 12.17 months (95% CI = 9.07–15.11 months, P < .0001).
Mean duration of time without significant symptoms of toxicity was 33.15 months (95% CI = 30.82–35.49 months) in the olaparib group vs 20.24 months (95% CI = 17.36–23.11 months) in the placebo group. The between-group difference was 12.92 months (95% CI = 9.30–16.54 months, P < .0001).
The investigators concluded, “The substantial progression-free survival benefit provided by maintenance olaparib in the newly diagnosed setting was achieved with no detrimental effect on patients’ [health-related quality of life] and was supported by clinically meaningful quality-adjusted progression-free survival and [time without significant symptoms of toxicity] benefits with maintenance olaparib vs placebo.”
Michael Friedlander, MD, of the University of New South Wales Clinical School, Prince of Wales Hospital, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by AstraZeneca and Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.
