Certain Biomarkers Predict Immunotherapy Responses in Patients With NSCLC

Results from a recent study suggest the use of integrated tumor microenvironment-based biomarkers to effectively predict responses to immunotherapy in patients with advanced non–small-cell lung cancer (NSCLC; JAMA Netw Open. 2019;2[7]:e196879).

“The beneficial role of immunotherapy and the clinical relevance of current biomarkers in non–small cell lung cancer…remain inconclusive; thus, appropriate strategies and reliable predictors need further definition,” according to lead investigator Yunfang Yu, MD, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Guangzhou, China, and colleagues.

Thus, Dr Yu et al sought to assess the relationship between clinical outcomes and immune checkpoint inhibitors, tumor vaccines, and cellular immunotherapy in patients with advanced NSCLC. They also wanted to explore appropriate strategies, candidates, and predictors.

Predicting Immunotherapy Response

Using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases, the investigators collected data from  randomized clinical trials of overall survival (OS), progression-free survival (PFS), or objective response rate with immune checkpoint inhibitors, tumor vaccines, or cellular immunotherapy versus conventional therapy in patients with advanced or metastatic NSCLC. There were 31 immunotherapy trials included, and multicohort data comprised next-generation sequencing data from patients with advanced NCSLC.

The primary end points of the study were OS and PFS, the survival increases of which were estimated with hazard ratios (HRs) and 95% CIs. Data were analyzed between February 1, 2018, and August 31, 2018.

Overall, there were 14,395 patients included in the meta-analysis, and 1833 patients included in the individual patient-level study. Immunotherapy led to a significantly longer OS than conventional therapy (HR, 0.76; 95%CI, 0.71-0.82; P <.001), with the same results seen for PFS (HR, 0.76; 95%CI, 0.70-0.83; P <.001). Of note, first-line pembrolizumab plus platinum-based chemotherapy was deemed the best checkpoint blockade strategy.

When combined, PD-L expression and tumor mutation burden (TMB) were tied to predictive prognosis (whole-exome sequencing: 1-year PFS area under the receiver operating characteristic curve [AUC], 0.829; 3-year PFS AUC, 0.839; targeted next-generation sequencing: 1-year PFS AUC, 0.826; 3-year PFS AUC, 0.948).

In addition, adding CD8+ T-cell tumor-infiltrating lymphocytes was also tied to improved prognostications for OS (3-year OS AUC, 0.659; 5-year OS AUC, 0.665).

Promising Regimens and Biomarkers

“Pembrolizumab with platinum-based chemotherapy was found to be the most appropriate first-line immune checkpoint inhibitor regimen for advanced NSCLC, and the combined use of PD-L1 expression and TMB was found to be a promising biomarker to evaluate patients’ survival and response to precision immunotherapy,” Dr Yu and colleagues reported.

“The further combination of CD8+ T-cell tumor-infiltrating lymphocytes, PD-L1 expression, and TMB was associated with reliable prognosis,” they concluded, adding that the prognostic value of that combination needs to be validated in large-scale trials.—Hina Khaliq