2064 - Phase III trial of Lurbinectedin versus PLD or Topotecan in platinum-resistant ovarian cancer patients: Results of CORAIL trial

Background

Lurbinectedin (L) is a new anticancer agent that blocks transcriptional transactivation, induces DNA double-strand breaks, and modulates the tumor microenvironment. L showed activity in platinum-resistant ovarian cancer (PROC) patients (pts) in a randomized phase II trial in comparison to topotecan (Ann Oncol 2017; 28:1280).

Methods

Pts with PROC [platinum-free interval [PFI] 1-6 months (mo) after last platinum chemotherapy (CT)] treated with ≤3 prior CT lines and ECOG PS 0-2 were eligible. Enrolled pts were randomly assigned (1:1) to receive L 3.2 mg/m² q3wk (Arm A), or investigator choice of PLD (P) 50 mg/m² q4wk or topotecan (T) 1.5 mg/m²/day D1-5 q3wk (Arm B) until progression or discontinuation due to toxicity. Pts were stratified by ECOG PS (0 vs ≥ 1), PFI (1-3 vs > 3-6 mo) and prior CT lines (1-2 vs 3). The primary endpoint was PFS by independent review committee (IRC). Sample size was calculated to demonstrate a 30% reduction in the relative risk of progression or death. The secondary endpoints of ORR, OS, and patient-reported outcomes are also reported.

Results

442 pts were randomized; 221 in each arm. Baseline characteristics were well balanced including median prior CT (n = 2) with the following differences (Arm A/B): median age 63/59 years; serous histology 82/90%; ascites 41/50%; and use of prior bevacizumab 40/46%. Median (95% CI) PFS by IRC was 3.5 mo in arm A vs 3.6 mo in arm B (HR 1.04, 95% CI 0.84-1.29). ORR by IRC was 14.0% (9.7-19.3%) in arm A vs 12.2% (8.2-17.3%) for arm B (p=NS). Interim OS was 11.2 mo in arm A vs 11.1 mo in arm B (HR 0.97, 95% CI 0.77-1.23). Related adverse events (AEs) were reported in 201/219 pts (92%) in Arm A vs 198/213 (93%) in Arm B; grade ≥ 3 AEs in 105 (48%) vs 136 (64%) (p = 0.001), respectively. In arm B, T accounted for a higher percentage of AEs than P. Treatment-related dose reductions, delays and discontinuations were more frequent in Arm B. Global QoL scores were not different between the arms.

Conclusions

Although the primary endpoint (30% of reduction in PFS) 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 PROC setting.

Clinical trial identification

NCT02421588.

Legal entity responsible for the study

PharmaMar SA.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

S. Gaillard: Consulting or advisory role: Pfizer, Genentech/Roche, Merck, Tesaro; Patents, royalties, other intellectual property: Sermonix Pharmaceuticals; Honoraria: Merck; Research funding: TetraLogic Pharmaceuticals, PharmaMar, Bristol-Myers Squibb, Gradalis, Merck, Genentech/Roche, Iovance Biotherapeutics. I.L. Ray-Coquard: Consulting or advisory role: Pfizer, Abbvie, Amgen Honoraria: Roche, PharmaMar, AstraZeneca. I.B. Vergote: Consulting or advisory role: AstraZeneca, Amgen, Array Biopharma, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Lilly, GE Healthcare, Genentech, GlaxoSmithKline, Intuitive Surgical, Janssen-Cilag, MedImmune, Menarini, Merck Sharp & Dohme, Morphotek, Nektar, Novo Nordisk, Oasmia Pharmaceutical AB, PharmaMar, Phillips Gilmore Oncology, Roche, Sanofi, Schering-Plough; Travel, accommodations, expenses: GCI Health, Roche, Oasmia Pharmaceutical AB, PharmaMar, AstraZeneca; Research funding: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Exelixis, Fresenius Biotech, GlaxoSmithKline, Ipsen, Janssen-Cilag, Merck Sharp & Dohme, Merrimack, Morphotek, Nektar, Nerviano Medical, Sciences, Novartis, Pfizer, Quintiles, Roche, Sandoz, Sanofi, Schering-Plough, Vifor Pharma, Wyeth, MedImmune, Genmab, Karyopharm Therapeutics, Tesaro. N. Colombo: Consulting or advisory role: Roche/Genentech, PharmaMar, Amgen, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology. S.A. Ghamande: Consulting or advisory role: Advaxis; Speakers' bureau: Advaxis; Research funding: Advaxis, GlaxoSmithKline, AstraZeneca, Tesaro, PharmaMar, Teueda, Merck and Co Inc. A. Soto-Matos, C. Kahatt, J. Gomez, A. Nieto: Employee and stock: PharmaMar. C.M. Fernandez, N. Torres: Employee PharmaMar. R.S. Kristeleit: Consulting or advisory role: Clovis Oncology, Roche/Genentech, Sotio, Cerulean Pharma, Basilea; Travel, accommodations, expenses: Clovis Oncology, Basilea, Valirx; Honoraria: Clovis Oncology, Roche/Genentech, AstraZeneca, Tesaro. D.M. O'Malley: Honoraria: Clovis Oncology; Consulting or advisory role: Janssen Oncology, AstraZeneca, Clovis Oncology, Amgen, Tesaro, Novocure, Myriad Genetics, Abbvie; Research funding: Amgen, VentiRx, AstraZeneca, Genentech/Roche, Regeneron, ImmunoGen, Janssen; Research & Development: Clovis Oncology, EMD Serono, Ergomed, Ajinomoto, ImmunoGen, Janssen, Cerulean Pharma, Array BioPharma, Agenus, Tesaro, Tracon Pharma, Stem CentRx, Bristol Myers Squibb, PharmaMar. All other authors have declared no conflicts of interest.