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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

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  • Bradley J Monk
  • Rachel N Grisham
  • Susana Banerjee
  • Elsa Kalbacher
  • Mansoor Raza Mirza
  • Ignacio Romero
  • Peter Vuylsteke
  • Robert L Coleman
  • Felix Hilpert
  • Amit M Oza
  • Anneke Westermann
  • Martin K Oehler
  • Sandro Pignata
  • Carol Aghajanian
  • Nicoletta Colombo
  • Esther Drill
  • David Cibula
  • Kathleen N Moore
  • Janna Christy-Bittel
  • Josep M Del Campo
  • Regina Berger
  • Christian Marth
  • Jalid Sehouli
  • David M O'Malley
  • Cristina Churruca
  • Adam P Boyd
  • Gunnar Kristensen
  • Andrew Clamp
  • Isabelle Ray-Coquard
  • Ignace Vergote
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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 = 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.

Original languageEnglish
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Issue number32
Pages (from-to)3753-3762
Number of pages10
Publication statusPublished - 10 Nov 2020

ID: 60987441