Efficacy and safety of camrelizumab plus apatinib in previously treated patients with advanced non-small cell lung cancer harboring EGFR or ALK genetic aberration

Guanghui Gao, Jian Ni, Yina Wang, Shengxiang Ren, Zhihua Liu, Gongyan Chen, Kangsheng Gu, Aimin Zang, Jun Zhao, Renhua Guo, Jianxing He, Xiaoyan Lin, Yueyin Pan, Zhiyong Ma, Zhehai Wang, Min Fan, Yunpeng Liu, Shundong Cang, Xinfeng Yang, Weixia Li, Quanren Wang, Caicun Zhou, Guanghui Gao, Jian Ni, Yina Wang, Shengxiang Ren, Zhihua Liu, Gongyan Chen, Kangsheng Gu, Aimin Zang, Jun Zhao, Renhua Guo, Jianxing He, Xiaoyan Lin, Yueyin Pan, Zhiyong Ma, Zhehai Wang, Min Fan, Yunpeng Liu, Shundong Cang, Xinfeng Yang, Weixia Li, Quanren Wang, Caicun Zhou

Abstract

Background: Camrelizumab plus apatinib shows encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced non-small cell lung cancer (NSCLC); however, clinical benefits from this combination regimen in NSCLC patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) have not been reported. We assessed the efficacy and safety of this combined regimen in pretreated patients with advanced NSCLC and defined EGFR/ALK status (EGFR+/ALK+) in a phase 1b/2 trial.

Methods: Previously treated patients with advanced EGFR+/ALK+ NSCLC were enrolled and given camrelizumab 200 mg intravenously every 2 weeks plus apatinib at the recommended dose of 250 mg orally once daily. Patients harboring sensitive EGFR mutations or ALK fusion genes had received at least one EGFR/ALK TKI and a platinum-based chemotherapy regimen before the enrollment. The primary endpoint was objective response rate (ORR).

Results: All 43 enrolled patients comprised the efficacy and safety analysis population. The confirmed ORR was 18.6% (95% CI: 8.4-33.4%) and the clinical benefit response rate was 27.9% (95% CI: 15.3-43.7%). Median progression-free survival (PFS) was 2.8 months (95% CI: 1.9-5.5 months) and median overall survival was not reached (95% CI: 7.3 months-not reached), with a median follow-up period of 15.7 months (range, 0.5-24.4 months). The most common grade ≥3 treatment-related adverse events (TRAEs) were hypertension (16.3%), proteinuria (11.6%) and palmar-plantar erythrodysaesthesia syndrome (9.3%). No unexpected adverse events were recorded.

Conclusions: Camrelizumab plus apatinib showed moderate antitumor activity and acceptable safety profile in previously treated patients with advanced NSCLC and EGFR or ALK genetic aberrations, which warranted further validation.

Trial registration: ClinicalTrials.gov identifier: NCT03083041. Registered March 17, 2017.

Keywords: Apatinib; Camrelizumab; PD-L1 expression; immunotherapy.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-22/coif). All authors report that this study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd. QW, WL, and XY were employees of Jiangsu Hengrui Pharmaceuticals Co., Ltd. CZ serves as an unpaid editorial board member of Translational Lung Cancer Research from August 2020 to July 2022. The authors have no other conflicts of interest to declare.

2022 Translational Lung Cancer Research. All rights reserved.

Figures

Figure 1
Figure 1
Flow chart of patients with advanced EGFR+/ALK+ non-small cell lung cancer (n=43). EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase.
Figure 2
Figure 2
Clinical activity of camrelizumab plus apatinib in advanced non-small cell lung cancer patients harboring EGFR or ALK genetic aberrations. (A) Best percentage changes in sum of the diameters of target lesion from baseline. (B) Treatment duration and tumor response in 8 responders (0 CR and 8 PR). EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; CR, complete response; PR, partial response; PD, progressive disease. Red asterisks indicated confirmed responses.
Figure 3
Figure 3
PFS and OS in advanced non-small cell lung cancer patients harboring EGFR or ALK genetic aberrations (n=43). (A) Kaplan-Meier curves for PFS; (B) Kaplan-Meier curves for OS. EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; PFS, progression-free survival; OS, overall survival; CI, confidence interval; NR, not reached.

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