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

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 ac...

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Bibliographic Details
Published in:	Journal of clinical oncology Vol. 38; no. 32; p. 3753
Main Authors:	Monk, Bradley J, Grisham, Rachel N, Banerjee, Susana, Kalbacher, Elsa, Mirza, Mansoor Raza, Romero, Ignacio, Vuylsteke, Peter, Coleman, Robert L, Hilpert, Felix, Oza, Amit M, Westermann, Anneke, Oehler, Martin K, Pignata, Sandro, Aghajanian, Carol, Colombo, Nicoletta, Drill, Esther, Cibula, David, Moore, Kathleen N, Christy-Bittel, Janna, Del Campo, Josep M, Berger, Regina, Marth, Christian, Sehouli, Jalid, O'Malley, David M, Churruca, Cristina, Boyd, Adam P, Kristensen, Gunnar, Clamp, Andrew, Ray-Coquard, Isabelle, Vergote, Ignace
Format:	Journal Article
Language:	English
Published:	United States 10.11.2020
Subjects:	Adult Aged Benzimidazoles - adverse effects Benzimidazoles - therapeutic use Cystadenocarcinoma, Serous - drug therapy Cystadenocarcinoma, Serous - enzymology Cystadenocarcinoma, Serous - pathology Doxorubicin - analogs & derivatives Doxorubicin - therapeutic use Fallopian Tube Neoplasms - drug therapy Fallopian Tube Neoplasms - enzymology Fallopian Tube Neoplasms - pathology Female Humans MAP Kinase Kinase 1 - antagonists & inhibitors MAP Kinase Kinase 2 - antagonists & inhibitors Middle Aged Neoplasm Grading Neoplasm Recurrence, Local - drug therapy Ovarian Neoplasms - drug therapy Ovarian Neoplasms - enzymology Ovarian Neoplasms - pathology Paclitaxel - therapeutic use Peritoneal Neoplasms - drug therapy Peritoneal Neoplasms - enzymology Peritoneal Neoplasms - pathology Polyethylene Glycols - therapeutic use Progression-Free Survival Protein Kinase Inhibitors - adverse effects Protein Kinase Inhibitors - therapeutic use Topotecan - therapeutic use Young Adult
ISSN:	1527-7755, 1527-7755
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Summary:	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. 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. 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 mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. 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 mutation might predict response to binimetinib.
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ISSN:	1527-7755 1527-7755
DOI:	10.1200/JCO.20.01164