Abstract
BackgroundClinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown.MethodsPatients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: (1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and (2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups.ResultsAmong a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8–7.7 months) and overall survival (OS) (11.4 months, 95% CI 7.4–27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1–7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6–29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0–1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC.ConclusionsICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.
Highlights
The emergence of immune checkpoint inhibitors (ICIs) has led to major changes in treatment paradigms for nonsmall cell lung cancer (NSCLC)
The uNSCLC group had a median age of 66 years, and most patients were men (95%), and most had a smoking history (95%) and good Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0–1 (82%)
The data are expressed as number (%) and median compared with NSCLC with common histology (cNSCLC), common non-small cell lung cancer; ECOG-PS, Eastern Cooperative Oncology Group performance status; LCNEC, large cell neuroendocrine carcinoma; NA, not available; PD-L1, programmed death ligand-1; TPS, tumor proportion score; uNSCLC, uncommon non-small cell lung cancer respectively
Summary
The emergence of immune checkpoint inhibitors (ICIs) has led to major changes in treatment paradigms for nonsmall cell lung cancer (NSCLC). Adenocarcinoma and squamous cell carcinoma are the dominant tumor pathologies in NSCLC, 8–18% of patients have uncommon histology, such as pleomorphic carcinoma, large cell neuroendocrine carcinoma (LCNEC), large cell carcinoma and not otherwise specified (NOS) [10,11,12,13]. Patients with NSCLC-NOS are reported to have a median PFS of 5.9 months after first-line platinum-based chemotherapy, which is shorter than 7.3 months in patients with adenocarcinoma [15]. Patients with LCNEC have better clinical benefit from small cell lung cancer (SCLC)-based chemotherapy, such as etoposide/platinum, compared with NSCLC-based chemotherapy, such as gemcitabine/platinum, pemetrexed/platinum and paclitaxel/platinum [16]. Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown
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