Morphological, immune and genetic features in biopsy sample associated with the efficacy of pembrolizumab in patients wi
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ORIGINAL ARTICLE – CLINICAL ONCOLOGY
Morphological, immune and genetic features in biopsy sample associated with the efficacy of pembrolizumab in patients with non‑squamous non‑small cell lung cancer Tetsuya Sakai1,2,3 · Hibiki Udagawa1 · Shingo Matsumoto1 · Kiyotaka Yoh1 · Kaname Nosaki1 · Takaya Ikeda1 · Yoshitaka Zenke1 · Keisuke Kirita1 · Seiji Niho1 · Tetsuo Akimoto2,4 · Koichi Goto1 · Genichiro Ishii2,3 Received: 5 August 2020 / Accepted: 24 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Introduction The usefulness of the histopathology of biopsy samples for predicting the efficacy of immunotherapy in nonsquamous, non-small cell lung cancer (NSq NSCLC) patients remains unclear. Methods We retrospectively investigated the associations between the histopathological features in biopsy samples and survival outcomes in advanced NSq NSCLC patients receiving pembrolizumab. NSq NSCLC was classified histopathologically as morphological adenocarcinoma or non-small cell carcinoma (NSCC: absence of definitive features of either adenocarcinoma or a squamous morphology). We investigated the association between the tumor morphological features and immune/genetic features by examining the tumor PD-L1 expression and tumor mutation burden (TMB). Results Among 33 advanced NSq NSCLC patients with tumor PD-L1 scores ≥ 50% receiving pembrolizumab as first-line therapy, a biopsy diagnosis of NSCC was associated with a significantly longer progression-free survival [median 16.8 vs. 2.3 months; hazard ratio (HR) 0.26; 95% CI 0.10–0.62, P = 0.01] and overall survival (median NR vs. 10.1 months; HR 0.35; 0.12–0.97, P = 0.04) as compared to that of morphological adenocarcinoma. In an analysis of 367 biopsy samples, the NSCC group showed a higher percentage of samples with PD-L1 scores ≥ 50% than the morphological adenocarcinoma group (35% vs. 10%). The NSCC group (n = 8) also showed a significantly higher TMB than the morphological adenocarcinoma group (n = 7) (median 236 vs. 25 mutations/whole exome, P = 0.01). Conclusion Absence of definitive morphological features in a biopsy sample could be a useful predictor of the efficacy of pembrolizumab in NSq NSCLC patients with tumor PD-L1 scores ≥ 50%, as these tumors are likely to show high tumor PD-L1 expression and high TMB. Keywords Lung cancer · Pembrolizumab · Morphological features · PD-L1 · TMB
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03413-5) contains supplementary material, which is available to authorized users. * Hibiki Udagawa [email protected] 1
Department of Thoracic Oncology, National Cancer Center Hospital East, 6‑5‑1 Kashiwanoha, Kashiwa, Chiba 277‑0882, Japan
2
Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
3
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan
4
Department of Radiation Oncology and Particle Therapy, National Ca
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