Binimetinib/Erlotinib Shows Tolerability in EGFR- or KRAS-Mutated NSCLC

Video

Andreas Saltos, MD, discusses a phase 1 trial of binimetinib and erlotinib for patients with non–small cell lung cancer and EGFR or KRAS mutations.

Andreas Saltos, MD, medical oncologist and clinical research medical director in the department of thoracic oncology at Moffitt Cancer Center, discusses a phase 1 trial (NCT01859026) of binimetinib (Mektovi) and erlotinib (Tarceva) for patients with non–small cell lung cancer (NSCLC) and EGFR or KRAS mutations.

The study investigators were looking at whether the combination of binimetinib and erlotinib showed safety and efficacy for patients with NSCLC. Erlotinib is an EGFR inhibitor used as targeted therapy for NSCLC, while the MEK inhibitor binimetinib is not currently approved for NSCLC. Saltos says that investigators theorized that dual inhibition of the MAP kinase pathway would have efficacy in patients with EGFR mutations as well as KRAS mutations, which have limited targeted therapies available.

Of a total of 43 patients enrolled in the phase 1 or 1b parts of the trial, 17 (40%) had an EGFR mutation, while 22 (51%) had a KRAS mutation. According to Saltos, investigators performed dose escalation of both drugs until they determined a recommended phase 2 dose. The safe dose was lower than the dosage each drug was approved for individually: 100 mg of erlotinib daily and 15 mg of binimetinib twice daily for 5 days a week. The toxicity was manageable, and investigators did not observe any significant drug interactions.

TRANSCRIPTION:

0:08 | Our group here at Moffitt Cancer Center conducted this phase 1/1b clinical trial exploring the use of binimetinib, which is a MEK inhibitor, with erlotinib, an improved EGFR inhibitor, in patients with NSCLC harboring either KRAS or EGFR mutations.

The rationale for the study came from the observation that a patients with EGFR-mutant lung cancer inevitably develop resistance to EGFR inhibitors, and patients with KRAS mutations make up a large population of patients with this driver, KRAS, which until recently was undruggable. And with the theory that with dual inhibition in the MAP kinase pathway, where there's activation in both populations, we might be able to achieve better tumor control or better responses.

1:13 | In this phase 1 trial, we first were able to ramp up from a low doses of both drugs. And in our case, actually, we had to tune the doses down until we found ultimately a slightly lower dose than what's the approved use for both drugs was needed to manage the [adverse event] profile. Ultimately, we found that the dose of erlotinib, 100 mg daily with binimetinib, 15 mg twice a day, for 5 days a week, was our maximum tolerated dose or recommended phase 2 dose.

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