Does First-Line Targeted Therapy Plus Immunotherapy Produce Durable Responses in ALK-Positive NSCLC?
A recent study assessed whether combining a targeted therapy with an immunotherapy for anaplastic lymphoma kinase (ALK) translocation-positive advanced non-small cell lung cancer (NSCLC) results in more durable patient responses.
The study will be published in the Journal of Thoracic Oncology (online March 5, 2018; doi:10.1016/j.jtho.2018.02.022).
The ALK kinase inhibitor crizotinib has demonstrated efficacy in the first-line setting for ALK translocation-positive advanced NSCLC. However, a majority of patients progress after receiving this targeted therapy. A common belief is that combining targeted therapy with an immunotherapy—such as the programmed death-1 (PD-1) inhibitor nivolumab—may result in better outcomes for these patients, due to nivolumab’s previously-demonstrated association with durable responses and long-term overall survival in patients with NSCLC.
David R Spigel, MD, Sarah Cannon Research Institute (Nashville, TN), and colleagues conducted a study assessing nivolumab plus crizotinib in patients with previously untreated advanced ALK translocation-positive NSCLC. Researchers comprised a single-arm cohort (Group E) to evaluate the safety of first-line nivolumab (240 mg once every 2 weeks) plus crizotinib (250 mg twice daily).
The primary endpoint was safety, which would be met if less than or equal to 20% of patients discontinued treatment due to adverse events by week 17. The secondary endpoint was objective response rate.
A planned safety review occurred in November 2016, and the data cutoff was May 26, 2017.
Researchers reported that among the first 13 patients treated with nivolumab plus crizotinib, 38% (n = 5) developed severe hepatic toxicities leading to discontinuation of treatment. Among these patients, two died and a likely contributor to death was the presence of severe hepatic toxicities. Researchers closed enrollment of the study and combination treatment was discontinued for all patients due to observed grade 3 or higher hepatic toxicities.
Five patients (38%) demonstrated partial response, researchers noted.
Dr Spigel and colleagues concluded that the combination of crizotinib plus nivolumab is not a safe or effective treatment strategy for patients with advanced ALK translocation-positive NSCLC. Further research is needed to explore other combination strategies to improve durable response rates for such patients.—Zachary Bessette