Prognostic Value of / Status for Overall Survival in First-Line Monoimmunotherapy and Chemoimmunotherapy Treated Patients With Nonsquamous NSCLC in the Netherlands: A Brief Report.

INTRODUCTION

Programmed death-ligand 1 (PD-L1) is the main predictive biomarker used to identify patients with NSCLC who are eligible for treatment with immune checkpoint inhibitors. Despite its utility, the predictive capacity of PD-L1 is limited, necessitating the exploration of supplementary predictive biomarkers. In this report, we describe the prognostic value of / mutation status for overall survival (OS) in patients with NSCLC treated with first-line immunotherapy or combined chemoimmunotherapy.

METHODS

Clinical data of all patients diagnosed with metastatic nonsquamous NSCLC in the Netherlands between January 1 and December 31 of 2019 were retrieved from the Netherlands Cancer Registry and linked to pathology reports of the Dutch Nationwide Pathology Databank. A total of 694 patients with available and mutation status and treated with first-line pembrolizumab or chemoimmunotherapy were included, with a median follow-up time of 42.5 months. Patients with an or mutation or , or fusion were excluded from the analysis.

RESULTS

Among patients treated with first-line pembrolizumab or chemoimmunotherapy, mutations in and occurred in 48.8% (n = 339) and 58.4% (n = 405), respectively. OS differed significantly between / mutational subgroups in patients treated with first-line pembrolizumab or chemoimmunotherapy (log-rank test,  = 0.007). Median OS of pembrolizumab or chemoimmunotherapy treated patients with mutated was longer in patients with -wildtype (485 versus 359 d, hazard ratio [HR] = 0.76,  = 0.028) or mutated (571 versus 447 d, HR = 0.73,  = 0.019). In a separate analysis of treatment subgroups, mutated was associated with longer median OS in chemoimmunotherapy treated -wildtype patients (468 versus 341 d, HR = 0.71,  = 0.029) but not in monoimmunotherapy treated patients with -wildtype (512 versus 371 d, HR = 0.91,  = 0.78). In multivariable Cox regression analysis including age, sex, clinical disease stage, and PD-L1 tumor proportion score, / mutation status was no longer associated with OS.

CONCLUSIONS

Among patients with metastatic NSCLC who are treated with pembrolizumab or chemoimmunotherapy, the presence of a pathogenic and mutation is associated with longer OS. Nevertheless, in multivariable Cox regression analysis including age, sex, clinical disease stage, and PD-L1 tumor proportion score, / mutation status was no longer associated with OS.