Overall response rate (ORR) is low for patients with non-small cell lung cancer (NSCLC) with RET rearrangements after targeted therapy, according to research published in the Journal of Clinical Oncology (March 13, 2017; doi:10.1200/JCO.2016.70.9352).
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Multikinase inhibitors are commonly used to target mutations in EGFR, BRAF, and ROS1 mutations in NSCLC. While prospective trials provide limited data for NSCLC driven by rare genomic alterations, registries can offer complementary information on responses to targeted therapies.
Oliver Gautschi, MD, Cantonal Hospital Lucerne (Switzerland), and colleagues established the Global, Multicenter RET Registry (GLORY) to evaluate the use of Multikinase inhibitors in patients with RET-rearranged NSCLC. A total of 165 patients with any stage of NSCLC with RET rearrangements were sampled. Fifty-three patients underwent targeted therapy with agents including cabozantinib, vandetanib, sunitinib, sorafenib, alectinib, lenvatinib, nintedanib, ponatinib, and regorafenib. Patients were a median age of 51 years, 63% were never smokers, 98% had adenocarcinoma, and 72% had stage IV NSCLC at diagnosis. Rearrangements included KIF5B-RET (72%), CCDC6-RET (23%), NCOA4-RET (2%), EPHA5-RET (1%), and PICALM-RET (1%). The primary endpoint was best objective response.
A majority of patients were treated with cabozantinib (n = 21), which resulted in a complete response in 5%, partial response in 32%, and stable disease in 26%. Among those treated with vandetanib (n = 11) and sunitinib (n = 10), no complete responses were observed, limited partial responses were observed (18% and 22%, respectively), and limited stable disease was reported (27% and 33%, respectively). Median progression-free survival was 2.2 months (95% CI, 0.7-0.5 months) and median overall survival (OS) was 6.8 months (95% CI, 1.1 months-not reached). Individual median OS per targeted agent was 4.9 months with cabozantinib, 10.2 months with vandetanib, and 6.8 months with sunitinib.
Researchers concluded that the proportion of ORR for patients treated with targeted therapy for RET-rearranged NSCLC was lower than that observed with targeted therapy for EGFR-mutant and ALK-rearranged NSCLC in previous trials. They believe that suboptimal inhibition of RET kinase and the molecular intricacies of NSCLC could explain the low observed response rate. “New therapeutic approaches and an improved understanding of tumor biology and response are needed,” researchers said. – Zachary Bessette
