MILO/ENGOT-ov11: Binimetinib versus physician’s choice chemotherapy in recurrent or persistent low-grade serous carcinomas of the ovary, fallopian tube, or primary peritoneum Journal Article


Authors: Monk, B. J.; Grisham, R. N.; Banerjee, S.; Kalbacher, E.; Mirza, M. R.; Romero, I.; Vuylsteke, P.; Coleman, R. L.; Hilpert, F.; Oza, A. M.; Westermann, A.; Oehler, M. K.; Pignata, S.; Aghajanian, C.; Colombo, N.; Drill, E.; Cibula, D.; Moore, K. N.; Christy-Bittel, J.; del Campo, J. M.; Berger, R.; Marth, C.; Sehouli, J.; O’Malley, D. M.; Churruca, C.; Boyd, A. P.; Kristensen, G.; Clamp, A.; Ray-Coquard, I.; Vergote, I.
Article Title: MILO/ENGOT-ov11: Binimetinib versus physician’s choice chemotherapy in recurrent or persistent low-grade serous carcinomas of the ovary, fallopian tube, or primary peritoneum
Abstract: PURPOSE Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician’s choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after $ 1 prior platinum-based chemotherapy but # 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to $ 12.0 months) versus 6.7 months (0.03 to $ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade $ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n 5 341; January 2019) were consistent. CONCLUSION Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib. Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
Journal Title: Journal of Clinical Oncology
Volume: 38
Issue: 32
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2020-11-10
Start Page: 3753
End Page: 3762
Language: English
DOI: 10.1200/jco.20.01164
PUBMED: 32822286
PROVIDER: scopus
PMCID: PMC7655017
DOI/URL:
Notes: Article -- Export Date: 1 December 2020 -- Source: Scopus
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  1. Rachel Nicole Grisham
    170 Grisham
  2. Esther Naomi Drill
    93 Drill