Inhibitors of PD-1 in Non-Small Cell Lung Cancer: A Meta-Analysis of Clinical and Molecular Features.

Objective: PD-1 inhibitors have become an indispensable treatment in Non-Small Cell Lung Cancer (NSCLC), but the potential predictive value of clinical and molecular features need to be clarified. The objective of the study was to study the potency of PD-1 inhibitors in patients with NSCLC in contexts of both clinical and molecular features, and to aid identification of patients for choice of type of PD-1 inhibitor therapy in order to acquire more accurate NSCLC treatment in immunotherapy.

Method: PubMed, Google Scholar, Embase Science Direct, the Cochrane library, and major oncology conferences were searched for randomized clinical trials (RCTs) that were published prior to December 2021. RCTs that had PD-1 inhibitor alone or in combination with chemotherapy with non-PD-1 inhibitor for the treatment of NSCLC patients were selected. Two authors independently selected studies, data extraction and bias risk assessment. Basic characteristics of included studies, and also the 95% confidence interval and hazard ratios of the overall patients and subgroups were recorded. The inverse variance weighted method was used to estimate pooled treatment data.

Result: A total of eleven RCTs including 5,887 patients were involved. PD-1 inhibitors-based therapy substantially enhanced OS compared with non-PD-1 inhibitor therapy in patients with age group <65 years, 65-74 years, active or previous smokers, without brain metastases, liver metastases, EGFR wild-type patients, individuals in East Asia and U.S./Canada, but not in patients with age group ≥75 years, never smokers, brain metastases, EGFR mutant patients or individuals in Europe. OS was improved in patients with NSCLC who received PD-1 inhibitors regardless of their gender (male or female), histomorphological subtypes (squamous or non-squamous NSCLC), performance status (0 or 1), and PD-L1 tumor proportion score (TPS) (<1%, ≥1%, 1-49%, or ≥50%). An analysis of subgroups revealed that, patients with age group <65 years old, male, non squamous cell carcinoma, PS 1, TPS ≥1%, and TPS ≥50% benefited from pembrolizumab treatment not related with treatment line and treatment regimen.

Conclusion: Age group, smoking history, metastasis status/site, EGFR mutation status, and region can be used to predict the potency of PD-1 inhibitors, and to be individualized to choose different types of PD-1 inhibitors, and treatment regimen for NSCLC patients.