AACR 2018: Tumor Mutational Burden as Biomarker of Response to Immunotherapy in Lung Cancer
Posted: Thursday, May 3, 2018
A tumor mutational burden of ≥ 10 mutations/Mb was associated with an “enhanced response” to first-line therapy with nivolumab plus ipilimumab, regardless of PD-L1 expression, for patients with non–small cell lung cancer (NSCLC). These findings from the phase II CheckMate 568 trial presented at the 2018 Annual Meeting of the American Association for Cancer Research (AACR) in Chicago (Abstract CT078). The measurement of ≥ 10 mutations/Mb was chosen to define the tumor mutational burden for the co-primary efficacy endpoint in the phase III CheckMate 227 trial.
“This response rate, coupled with the known durability of responses to immuno-oncology agents, compares favorably to historical data with platinum-doublet chemotherapy,” concluded lead author Suresh Ramalingam, MD, of the Winship Cancer Institute at Emory University, and colleagues.
The investigators analyzed 288 patients with chemotherapy-naive stage IV NSCLC who received 3 mg/kg of nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks for up to 2 years. Excluded from the study were patients who had EGFR- and ALK-targetable NSCLC.
With a minimum follow-up of 3 months, the overall response rate was 27% in all treated patients, whereas the rate increased in patients with higher tumor mutational burden and plateaued with the threshold of ≥ 10 mutations/Mb. Overall response rates were 4%, 10%, 44%, and 39% in patients with tumor mutational burdens of < 5, < 10, ≥ 10, and ≥ 15 mutations/Mb, respectively. The safety profile for nivolumab plus ipilimumab was consistent with previous reports, and researchers observed no new safety signals.