Efficacy of ICIs on patients with oncogene-driven non-small cell lung cancer: a retrospective study

Xiaojin Guo,Menghang Yang,Jiayu Li,Fengying Wu,Anweng Xiong,Haiping Zhang,He Du

doi:10.20517/cdr.2021.85

Abstract

Aim: The objective of our study was to assess the efficacy of immune checkpoint inhibitors (ICIs) on patients with non-small-cell lung cancer (NSCLC) harboring oncogenic alterations. Methods: We retrospectively enrolled patients with advanced non-squamous NSCLC who were treated with anti-PD-1-based monotherapy or combined immunotherapy. Major characteristics including PD-L1 expression, treatment, and survival were analyzed. Results: In total, 309 non-squamous NSCLC patients with a median age of 61 years (range 20-88 years) including 70.9% male were retrospectively enrolled. The molecular alterations involved epidermal growth factor receptor (EGFR) (n = 81), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) (n = 31), anaplastic lymphoma kinase (ALK) (n = 1), human epidermal growth factor receptor 2 (HER2) (n = 12), V-raf murine sarcoma viral oncogene homolog (BRAF) (n = 2), rearranged during transfection (n = 4), and c-ros oncogene 1 (ROS1) (n = 3). In the EGFR subset, the ORR was 30.9% (n = 81) and PFS was significantly shorter than WT group (median PFS: 5.7 months vs. 7.1 months; P = 0.0061). In subgroup analyses, ICI combined therapy was significantly correlated with a longer PFS compared with ICI monotherapy (median PFS: 7.7 months vs. 4.7 months; P = 0.0112). In KRAS patients, ORR was 51.6% (n = 31). No significant difference was found in subgroup analyses. The ORR and PFS were 16.7% (n = 12) and 28.6% (n = 7), 7.8 months and 9.0 months for HER2 and EGFR Exon20 insertion patients, respectively. Three ROS1 patients were enrolled with a PFS of 16.0, 34.2, and 45.0 months individually, and one ALK patient with PFS of 4.4 months was identified. No response was found in two BRAF patients. Conclusion: ICI-based combination therapy can bring benefit to patients with EGFR-mutant NSCLC. ICI-based combination therapy could be considered for patients with ROS1 rearrangement, HER2 mutation and EGFR Exon20 insertion NSCLC.

Highlights

Lung cancer is the most common cancer worldwide, in terms of both incidence and mortality[1]
Immune checkpoint inhibitors (ICIs)-based combination therapy could be considered for patients with ros oncogene 1 (ROS1) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation and epidermal growth factor receptor (EGFR) Exon20 insertion non-small cell lung cancer (NSCLC)
309 non-squamous non-small cell lung cancer patients treated with anti-PD-1 based monotherapy or combined immunotherapy in Shanghai Pulmonary Hospital were identified

Summary

Introduction

Lung cancer is the most common cancer worldwide, in terms of both incidence and mortality[1]. The use of small molecule tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of patients with specific genomic aberrations[2,3,4,5]. Despite the high response of TKIs, acquired resistance inevitably occurs and limits the long-term benefits[6]. Once this happens, the subsequent anti-tumor treatment is limited. Whether ICIs alone or in combination with other therapies would bring benefit to those with driver mutations is still to be elucidated. Continued research is required to explore the optimal use of ICI therapy in patients with driver mutations to improve outcomes of this cohort

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