In an exploratory post hoc analysis reported in the Journal of Clinical Oncology, Amit M. Oza, MD, and colleagues found superior quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in patients with platinum-sensitive, recurrent ovarian carcinoma receiving maintenance rucaparib vs placebo in the phase III ARIEL3 trial.
The trial supported the April 2018 U.S. Food and Drug Administration approval of rucaparib for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
Amit M. Oza, MD
Study Details
In the trial, 564 patients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned 2:1 to receive rucaparib at 600 mg twice per day (n = 375) or placebo (n = 189).
QA-PFS represents the duration of progression-free survival adjusted for treatment toxicity and associated detrimental effects as reported by the patient. It was calculated as progression-free survival function × the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function.
Q-TWiST is an outcome that subtracts periods of treatment toxicity or disease symptoms from the survival endpoint (TWiST) and incorporates patient assessments of quality of life by weighting it with a patient-derived utility value. Q-TWiST analysis included TOX, defined as the mean duration in which a patient experienced grade ≥ 3 adverse events or the grade ≥ 2 adverse events of nausea, vomiting, fatigue, and asthenia. It was calculated as µTOX × TOX + TWiST, with µTOX calculated using EQ-5D-3L data.
Key Findings
Mean QA-PFS was significantly longer with rucaparib vs placebo, with differences of 6.28 months in the intent-to-treat population, 9.37 months in the BRCA-mutant subgroup (130 rucaparib vs 66 placebo), 7.93 months in the homologous recombination deficient (HRD) subgroup (236 rucaparib vs 118 placebo), and 2.71 months in the BRCA wild-type/loss of heterozygosity (LOH)-low subgroup.
“The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib vs placebo in all predefined cohorts.”— Amit M. Oza, MD, and colleagues
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With TOX defined using grade ≥ 3 adverse events, the difference in mean Q-TWiST for rucaparib vs placebo was 6.88 months in the intent-to-treat population, 9.73 months in the BRCA-mutant subgroup, 8.11 months in the HRD subgroup, and 3.35 months in the BRCA wild-type/LOH-low subgroup.
With TOX defined as grade ≥ 2 nausea, vomiting, fatigue, and asthenia, the difference in mean Q-TWiST for rucaparib vs placebo was 6.77 months in the intent-to-treat population, 9.56 months in the BRCA-mutant subgroup, 8.00 months in the HRD subgroup, and 6.00 months in the BRCA wild-type/LOH-low subgroup.
The investigators concluded, “The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib vs placebo in all predefined cohorts.”
Dr. Oza, of Princess Margaret Cancer Centre, University of Toronto, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Clovis Oncology and others. For full disclosures of the study authors, visit ascopubs.org.
