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. 2023 Aug 31;15(8):4172-4181.
doi: 10.21037/jtd-23-348. Epub 2023 Jul 24.

Efficacy and safety of immune checkpoint inhibitors in lung large-cell neuroendocrine carcinoma

Zheng Shi #  1   2 , Jingwen Wei #  1   2 , Manyi Xu #  1   3 , Zhengbo Song  1
Affiliations

Efficacy and safety of immune checkpoint inhibitors in lung large-cell neuroendocrine carcinoma

Zheng Shi et al. J Thorac Dis. .

Abstract

Background: Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare and highly aggressive neuroendocrine tumor. There is currently no standard therapeutic regimen, and systemic chemotherapy results in poor prognosis. Due to the rarity of L-LCNEC, the efficacy and safety of immune checkpoint inhibitors (ICIs) remain unclear.

Methods: This study included 34 L-LCNEC patients administered ICIs at Zhejiang Cancer Hospital, from February 6, 2018 to February 6, 2023. The treatment responses were evaluated. Fisher's exact test was used to compare categorical variables, and the Kaplan-Meier method was used for survival analyses. Cox regression was used for multivariate analysis.

Results: The objective response rate (ORR) of 34 patients was 29.4%, the disease control rate (DCR) was 82.4%, the median progression-free survival (PFS) was 6.30 months, and the median overall survival (OS) was 14.77 months. The ORRs of combined LCNEC (n=7) and pure LCNEC (n=27) were 14.3% and 33.3%; the DCRs were 100% and 77.8%; the median PFSs were 12.48 and 5.6 months (P=0.032); and the median OSs were 21.27 and 14.73 months, respectively (P=0.233). The observed incidence of immune-related adverse events (irAEs) was 61.8%, primarily occurring in grades 1/2 (58.8%) and grade 3 (5.9%). Elevated aminotransferases (14.7%), pneumonia (8.8%), and fatigue (8.8%) were the most common irAEs.

Conclusions: ICIs treatment showed efficacy and safety in advanced L-LCNEC, with the potential for greater benefits in the combined LCNEC subtype.

Keywords: Efficacy; immune checkpoint inhibitors (ICIs); immune-related adverse events (irAEs); lung large-cell neuroendocrine carcinoma (L-LCNEC); safety.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-348/coif). ZS reports that this study was funded by the Medical Scientific Research Foundation of Zhejiang Province (No. 2022KY653). ZS was sponsored by Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Swimmer plot of immune checkpoint inhibitors-treated lung LCNEC patients. LCNEC, large-cell neuroendocrine carcinoma; PR, partial response; SD, stable disease; PD, progressive disease.
Figure 2
Figure 2
Kaplan-Meier curves of PFS and OS according to treatments and pathological types. (A) PFS of first-line vs. second- and higher-line treatments. (B) OS of first-line vs. second- and higher-line treatments. (C) PFS of combined LCNEC vs. pure LCNEC patients. (D) OS of combined LCNEC vs. pure LCNEC patients. PFS, progression-free survival; OS, overall survival; LCNEC, large-cell neuroendocrine carcinoma.
See this image and copyright information in PMC

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