Brief Report: Phase I Results from a Study of Crizotinib in Combination with Erlotinib in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer.

Publication Type:

Journal Article


Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (2016)


INTRODUCTION: This phase I trial was conducted to determine the safety, maximum tolerated dose (MTD)/recommended phase II dose, and efficacy of crizotinib plus erlotinib in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

METHODS: NSCLC patients with an Eastern Cooperative Oncology Group performance status of 0-2 after failure of 1-2 prior chemotherapy regimens were eligible. Erlotinib 100 mg was given continuously once daily (QD) starting between day -14 and -7; crizotinib 200 mg twice daily (BID; dose level 1) or 150 mg BID (dose level -1) was added continuously beginning on treatment cycle 1, day 1. Potential pharmacokinetic interactions between crizotinib and erlotinib were evaluated.

RESULTS: Twenty-seven patients received treatment; 26 received crizotinib plus erlotinib. Common adverse events were diarrhea, rash, decreased appetite, and fatigue. Dose-limiting toxicities were dehydration, diarrhea, dry eye, dysphagia, dyspepsia, esophagitis and vomiting. The MTD was crizotinib 150 mg BID with erlotinib 100 mg QD. Crizotinib increased erlotinib area under the concentration-time curve 1.5-fold (dose level -1) and 1.8-fold (dose level 1). The crizotinib plasma level appeared to be unaffected by erlotinib coadministration. Two patients whose tumors harbored activating epidermal growth factor receptor mutations achieved confirmed partial responses, one at each crizotinib dose level.

CONCLUSIONS: The MTD of the crizotinib-erlotinib combination in patients with advanced NSCLC was crizotinib 150 mg BID with erlotinib 100 mg QD, below the approved dose of either agent. The phase II portion of the study was not initiated.