Cabozantinib, a multi-kinase RET inhibitor, demonstrated safety and efficacy for treating patients with RET-rearranged lung cancer in an open-label, phase 2 trial (ClinicalTrials.gov Identifier: NCT01639508), according to results presented at the International Association for the Study of Lung Cancer (IASLC) 17th Annual World Conference on Lung Cancer in Austria.1
RET rearrangements are found in 1% to 2% of non-small cell lung cancers (NSCLC). Researchers previously reported on cabozantinib’s safety and efficacy in the first stage of this trial at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO); the study has since completed accrual of both stages, with 26 patients treated.
Patients with stage IV pathologically confirmed lung cancers, the presence of an RET rearrangement, Karnofsky Performance Status (KPS) greater than 70%, and measurable disease were eligible for inclusion. Twenty-six patients were included; each was orally administered 60 mg of cabozantinib daily until either progression of disease or unacceptable toxicity.
The study’s primary objective was overall response rate (ORR), and the secondary objectives were progression-free survival (PFS), overall survival (OS), and toxicity.
The study met its primary endpoint with confirmed partial responses observed in 7 of 25 response-evaluable patients. The median PFS was 5.5 months, and the median OS was 9.9 months. In 26 patients evaluable for toxicity, the most common all-grade treatment-related adverse events were increased alanine aminotransferase (25 patients), increased aspartate aminotransferase (19 patients), hypothyroidism (18 patients), diarrhea (16 patients), and palmar plantar erythrodysesthesia (15 patients). Nineteen patients required dose reduction.
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The researchers concluded that cabozantinib is an active agent in patients with RET-rearranged lung cancers. They said that an improved understanding of tumor biology and novel therapeutic approaches is still required to improve outcomes with RET-directed therapy.
- Drilon A, Somwar R, Smith RS, et al. A Phase 2 study of cabozantinib for patients with advanced RET-rearranged lung cancers. Paper presented at: International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer; December 2016; Vienna, Austria.