Entrectinib Demonstrates Efficacy in Rare Lung Cancer, Pediatric Solid Tumors

A pair of study abstracts presented at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, supported the efficacy of entrectinib among 2 different groups of patients, including patients with a rare form of lung cancer and pediatric and adolescent patients with solid tumors.

The first abstract¹ reviewed data coming from 3 phase 1/2 single-arm clinical trials assessing the tyrosine kinase inhibitor among 53 patients with ROS1-mutated non—small cell lung cancer (NSCLC). Due to the rarity of the tumor type and therefore low feasibility of a randomized trial, the researchers identified 69 patients from the Flatiron Health electronic health record-derived database who were treated with crizotinib between January 1, 2011, and June 30, 2018, in order to compare the efficacy of the 2 drugs. Crizotinib is currently considered standard of care for the patient population.

“In situations where you’re dealing with vary rare molecularly defined subpopulations of cancer patients, it’s often difficult to conduct a randomized study because of the low feasibility of being able to identify and recruit enough patients,” explained Neal J. Meropol, MD, vice president of Research Oncology at Flatiron Health, and an author of the abstract, in an interview with The American Journal of Managed Care^®. “Given the availability of high-quality, real-world data, there is now the potential to gain insights into the treatment outcomes of patients who are cared for in routine clinical practice, as well as gain a potential comparator to the results of single-arm clinical trials.”

Comparing the 2 groups of patients, the researchers observed significantly longer time-to-treatment discontinuation therapy associated with entrectinib compared with crizotinib (14.6 months vs 8.8 months). Progression-free survival also favored entrectinib (weighted hazard ratio: 0.44; 95% CI: 0.27-0.74). With a median follow-up of 15.5 months, median overall survival (OS) associated with entrectinib was not reached. The median weighted OS with crizotinib was 18.5 months.

“These results using real-world data support the hypothesis that entrectinib has meaningful activity against lung tumors with ROS1 fusions and may be superior to current standard of care. While provocative, further study is certainly warranted to confirm these results,” said Meropol.

The second abstract² focused on the use of entrectinib in children between 4 months and 20 years with recurrent/refractory solid or central nervous system (CNS) tumors. Between May 2016 and October 2018, 29 patients with tumors with mutations in NTRK1/2/3, ROS1, or ALK, and neuroblastoma (NBL) were enrolled in the study and 28 were evaluated for response.

Among the 6 patients with CNS tumors, 1 achieved a complete response, 3 achieved a partial response, 1 achieved an unconfirmed partial response, and 1 has yet to be evaluated. There were 8 patients with extracranial solid tumors, of whom 6 had a fusion, with 1 achieving a complete response and 5 achieving a partial response. Among the 15 patients with NBL, 1 achieved a complete response.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors harboring NTRK1/2/3, ROS1, or ALK fusions (11 out of 11) as well as in an ALK-mutated NBL,” wrote the researchers. “No responses were seen in tumors lacking aberrations in targeted kinases.”

Based on the results, the researchers concluded that continued evaluation of entrectinib as a targeted therapy for solid tumors with these fusions, especially in high-grade CNS neoplasms, is warranted.

References:

1. Doebele R, Perez L, Trinh H, et al. Time-to-treatment discontinuation (TTD) and real-world progression-free survival (rwPFS) as endpoints for comparative efficacy analysis between entrectinib trial and crizotinib real-world ROS1 fusion-positive (ROS1+) NSCLC patients. Presented at: Presented at: 2019 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract: 9070.

2. Robinson G, Gajjar A, Gauvain K, et al. Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors. Presented at: 2019 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract: 10009.