Phase 3 Trial of Lurbinectedin vs Pegylated Liposomal Doxorubicin or Topotecan in Platinum-Resistant Ovarian Cancer Patients
Lurbinectedin is a novel agent that interferes with transcription, induces DNA double-strand breaks, and modulates the tumor microenvironment. In a previous randomized phase 2 trial, lurbinectedin was shown to have antitumor activity in platinum-resistant ovarian cancer patients, with patients having a significantly greater overall response rate (ORR) and progression-free survival (PFS) compared with topotecan.1 Here, Gaillard and colleagues present the results of the randomized, open-label, controlled phase 3 CORAIL trial, designed to evaluate the efficacy and safety of lurbinectedin versus pegylated liposomal doxorubicin (PLD) or topotecan in patients with platinum-resistant ovarian cancer.2
Included patients (n = 442) were those who had been treated with ≤3 prior chemotherapy lines, a platinum-free interval of 1 to 6 months after the last platinum chemotherapy, and who had an Eastern Cooperative Oncology Group performance status 0-2. Enrolled patients were randomly assigned (1:1) to receive lurbinectedin 3.2â€‰mg/m2 once every 3 weeks, or the investigatorâ€™s choice of PLD 50â€‰mg/m2 once every 4 weeks, or topotecan 1.5â€‰mg/m2/day (days 1-5, every 3 weeks) until progression or discontinuation due to toxicity. The primary end point was 30% reduction in PFS by independent review committee (IRC), with secondary end points of ORR, overall survival (OS), and patient-reported outcomes also reported.
The median PFS by IRC was 3.5â€‰months in patients receiving lurbinectedin versus 3.6â€‰months in patients receiving the other treatments (hazard ratio [HR], 1.04, 95% confidence interval [CI], 0.84-1.29; P = .8599). The ORR by IRC was 14.0% (9.7%-19.3%) in the lurbinectedin arm versus 12.2% (8.2%-17.3%) for the other treatment arm (P = not significant). The interim OS was 11.2â€‰months versus 11.1 months in patients receiving lurbinectedin versus other treatments, respectively (HR, 0.97; 95% CI, 0.77-1.23; P = .9329). ORR, PFS, and OS in patients with primary or secondary platinum resistance were also similar in the experimental and control arms (P = nonsignificant for all comparisons).
Percentages of related results were similar in both treatment arms, although the percentage of high-grade (grade ≥3) adverse events were greater in the treatment arm receiving other treatments (64%) than for lurbinectedin (48%; Pâ€‰=â€‰.001). Treatment-related dose reductions, delays, and discontinuations were more frequent in patients receiving PLD or topotecan than lurbinectedin, although global quality-of-life scores were not different between the arms.
Although the primary end point of this study was not met, the similar efficacy results between arms and the favorable safety profile indicate a potential role for lurbinectedin in the difficult-to-treat platinum-resistant ovarian cancer setting. Moreover, the real value of lurbinectedin may be in combination with other agents, including immunotherapy.
- Poveda A, et al. Ann Oncol. 2017;28(6):1280-1287.
- Gaillard S, et al. ESMO 2018. Abstract 932O.