Immunotherapy for Advanced Lung Cancer: Is Tumor Mutational Burden Linked to Response?
Posted: Monday, April 29, 2019
Patients with non–small cell lung cancer (NSCLC) and high tumor mutational burden responded well to first-line nivolumab plus ipilimumab irrespective of PD-L1 status, according to findings from the phase II CheckMate 568 trial, reported in the Journal of Clinical Oncology. Neal Ready, MD, PhD, of Duke University Medical Center, Durham, North Carolina, and colleagues suggested that a tumor mutational burden of at least 10 mutations per megabase (mut/Mb) may serve as an effective cutoff and biomarker for first-line treatment.
The authors treated 288 patients with recurrent, advanced NSCLC with nivolumab plus low-dose ipilimumab. Patients were categorized according to tumor PD-L1 expression (high: 1% or more; low: less than 1%). Overall, 252 patients (88%) were evaluable for PD-L1 expression, and 98 of 120 patients (82%) were evaluable for tumor mutational burden.
The overall response rate of the entire patient population was 30%. Patients with 1% or higher PD-L1 expression had an overall response rate of 41% versus 15% in patients with less than 1% PD-L1 expression. Overall response rates increased with increasing tumor mutational burden and leveled off at 10 mut/Mb. Patients with high and low PD-L1 expression plus a high tumor mutational burden had overall response rates of 48% and 47%, respectively. In contrast, patients with a low tumor mutational burden had overall response rates of 18% and 5%, respectively. Progression-free survival was 7.1 months in patients with a high tumor mutational burden versus 2.6 months in those with a low tumor mutational burden.
As for toxicity, grade 3 or 4 treatment-related adverse events were reported in 29% of patients, and 16% of study patients discontinued treatment as a result. Skin reactions were the most common immune-mediated adverse events related to treatment, occurring in 30% of patients.
Disclosure: The study authors’ disclosure information may be found at ascopubs.org.