Binimetinib study
The phase 3 MILO/ENGOT-ov11 study enrolled 341 patients with low-grade serous carcinomas of the ovaries, fallopian tubes, or peritoneum. Patients were randomized on a 2:1 basis to receive either binimetinib at 45 mg twice daily (n = 228) or physician’s choice of chemotherapy (n = 113). Chemotherapy consisted of pegylated liposomal doxorubicin at 40 mg/m2 on day 1 of each 28-day cycle; paclitaxel at 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle; or topotecan at 1.25 mg/m2 IV on days 1-5 of each 21-day cycle.
The efficacy analysis included 227 patients assigned to binimetinib and 106 assigned to chemotherapy.
A planned interim analysis was performed in 2016 after the first 303 patients were enrolled. At that time, the median PFS by blinded central review was 9.1 months in the binimetinib arm and 10.6 months in the physician’s choice arm (HR, 1.21; P = .807), so the trial was halted early for futility. Patients on active treatment at the time could continue until progression and were followed by local radiology.
At the interim analysis, secondary endpoints were also similar between the arms. The overall response rate was 16% in the binimetinib arm and 13% in the chemotherapy arm.
The most common grade 3 or greater adverse events with binimetinib were blood creatinine phosphokinase increase (26%) and vomiting (10%).
Dr. Grisham also reported updated follow-up results through January 2019.
The median PFS in the updated analysis was 11.2 months with the MEK inhibitor and 14.1 months with chemotherapy, a difference that was not statistically significant (HR, 1.12; P = .752). Updated overall response rates were the same in both arms, at 24%.
A post hoc molecular analysis of 215 patients suggested a possible association between KRAS mutation and response to binimetinib.
Two MEKs, one ‘meh’
Discussant Jubilee Brown, MD, of the Levine Cancer Institute at Atrium Health in Charlotte, N.C., said that “with a 2% to 5% chance of response in patients with low-grade serous ovarian cancer, there is a low bar for any compound to demonstrate success.”
Regarding the MILO/ENGOT-ov11 trial, she noted that “this study did not meet its primary endpoint, but perhaps the endpoint is not reflective of the importance of the study.”
A different outcome might have occurred had investigators stratified patients by KRAS status upfront, comparing patients with KRAS mutations treated with binimetinib to KRAS wild-type patients treated with either a MEK inhibitor or physician’s choice of care, Dr. Brown said.
She agreed with the assertion by Dr. Gershenson and colleagues that improved PFS qualifies trametinib to be considered a new option for standard care, ”especially in a rare tumor setting with limited options. This is a huge win for patients.”
The trametinib study was sponsored by NRG Oncology and the UK National Cancer Research Institute. Dr. Gershenson disclosed relationships with NRG Oncology, Genentech, Novartis, Elsevier, and UpToDate, as well as stock in several companies.
The binimetinib study was sponsored by Pfizer. Dr. Grisham disclosed relationships with Clovis, Regeneron, Mateon, Amgen, Abbvie, OncLive, PRIME, MCM, and Medscape. MDedge News and Medscape are owned by the same parent organization.
Dr. Brown disclosed consulting for Biodesix, Caris, Clovis, Genentech, Invitae, Janssen, Olympus, OncLive, and Tempus.
SOURCE: Gershenson DM et al. SGO 2020, Abstract 42; Grisham RN et al. SGO 2020, Abstract 41.