Article Text

Download PDFPDF

1 MILO/ENGOT-OV11: Phase-3 study of binimetinib versus physician’s choice chemotherapy (PCC) in recurrent or persistent low-grade serous carcinomas of the ovary, fallopian tube, or primary peritoneum
  1. R Grisham1,
  2. B Monk J2,
  3. S Banerjee3,
  4. R Coleman L4,
  5. A Oza M5,
  6. M Oehler K6,
  7. E Kalbacher7,
  8. M Mirza Raza8,
  9. J del Campo M9,
  10. C Marth10,
  11. A Westermann11,
  12. S Pignata12,
  13. N Colombo13,
  14. D Cibula14,
  15. F Hilpert15,
  16. C Aghajanian1,
  17. E Drill1,
  18. V Sandor16,
  19. A Boyd P17 and
  20. I Vergote18
  1. 1Memorial Sloan Kettering Cancer Center, Department of Medicine- Gynecologic Medical Oncology, New York, USA
  2. 2Arizona Oncology US Oncology Network- University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, USA
  3. 3Royal Marsden Hospital, Gynaecological Cancers at the Institute of Cancer Research, London, UK
  4. 4MD Anderson Cancer Center, Gynecologic Oncology and Reproductive Medicine, Houston, USA
  5. 5Princess Margaret Cancer Centre, Medical Oncology and Hematology, Toronto, Canada
  6. 6Royal Adelaide Hospital, Gynaecological Oncology, Adelaide- SA, Australia
  7. 7Centre Hospitalier Régional et Universitaire de Besançon, Oncology, de Besançon, France
  8. 8NSGO and Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  9. 9Vall d’Hebron University Hospital, Medical Oncology, Barcelona, Spain
  10. 10Innsbruck Medical University, Obstetrics and Gynecology, Innsbruck, Austria
  11. 11Amsterdam University Medical Centers, Dutch Gynaecological Oncology Group DGOG, Amsterdam, The Netherlands
  12. 12Istituto Nazionale Tumori Fondazione Pascale IRCCS, Medical Oncology, Naples, Italy
  13. 13Università Milano-Bicocca Direttore Programma Ginecologia Oncologica Istituto Europeo Oncologia, Dipartimento Medicina e Chirurgia, Milan, Italy
  14. 14First Faculty of Medicine- Charles University in Prague and General University Hospital in Prague, Obstetrics And Gynecology, Prague, Czech Republic
  15. 15Onkologisches Therapiezentrum am Krankenhaus, Gynecology, Jerusalem, Israel
  16. 16Array BioPharma Inc, Array, Boulder, USA
  17. 17Array BioPharma Inc, Biometrics and Clinical Operations, Boulder, USA
  18. 18Belgium and Luxemburg Gynaecological Oncology Group, Gynaecologic Oncology, Leuven, Belgium


Objectives Low-grade serous ovarian carcinomas (LGSOC) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30–60% of LGSOC. A phase II study of the MEK inhibitor selumetinib showed promising response rate of 15% in LGSOC and binimetinib, a potent MEK1/2 inhibitor, has demonstrated activity across multiple cancers.

Methods MILO (MEK-Inhibitor in Low-grade Serous Ovarian Cancer)/ENGOT-ov11 was an open-label, 2:1-randomized study of binimetinib (45-mg BID) vs PCC in LGSOC. Eligible patients had recurrent or persistent measurable LGSOC following ≥1 prior platinum-based chemotherapy, ≤3 prior chemotherapy lines, and no prior MEK-or BRAF-inhibitor. The primary endpoint was progression-free survival (PFS) by blinded central review; additional assessments: overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety.(NCT01849874).

Results 303 patients were randomized (201 binimetinib,102 PCC). Median PFS was 9.1 months (95% CI:7.3,11.3) for binimetinib and 10.6 months (95% CI:9.2,14.5) for PCC (HR:1.21(0.79,1.86);closed early for futility). Secondary efficacy endpoints were similar in the two groups: ORR 16%(complete/partial responses[CR/PRs]=32) vs 13%(CR/PRs=13); median DOR 8.1 (range:0.3–12.0+ months) vs 6.7 (0.3–9.7+ months); and median OS 25.3 vs 20.8 months, for binimetinib and PCC, respectively. Safety results were consistent with known safety profile of binimetinib; most common ≥grade 3 events were blood CK increased(20%) and hypertension(20%). Post-hoc analysis suggests a possible association between KRAS mutation and response to binimetinib.

Conclusions Although MILO did not meet its primary endpoint, binimetinib showed activity in LGSOC across the efficacy endpoints evaluated. Chemotherapy responses were higher than predicted. Further evaluation is warranted.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.