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

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.

Efficacy and safety of immunotherapy plus chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma

“…To further improve the prognosis in patients with LCNEC, we observed the e cacy of immunotherapy plus chemotherapy versus chemotherapy in these patients. Consistent with the retrospective study of ICIs alone [11,[22][23][24][25][26][27], our ndings also indicated a potential clinical bene t in patients treated with immunotherapy plus chemotherapy compared to chemotherapy (26.31 months VS. 16.95 months, P = 0.675). Owing to the data gap between the two groups and considering the bias caused by the patients' ECOG PS and tumor stage, the results of PSM showed a statistically signi cant difference (26.31 vs. 13.56 months, P = 0.041), which may better re ect the gap in clinical e cacy between the two groups.…”

“…In 2020, a retrospective study of 125 patients with LCNEC further demonstrated a longer survival bene t (mOS: 12.4 months vs. 6.0 months) in ICIs alone compared with those who did not receive ICIs [23]. In addition, several other retrospective studies have yielded similar results [11,22,[24][25][26][27]. Shirasawa et al con rmed that ICIs positively affect patients with LCNEC regardless of PD-L1 expression.…”

“…Immune checkpoint inhibitors (ICIs) are a class of monoclonal antibodies that mediate treatment properties by blocking immune checkpoints [18], including programmed death receptor 1 (PD-1)/programmed death receptor-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated protein 4, and other types of antibodies [19,20]. ICIs have demonstrated signi cant survival bene ts in various tumor types [21], and retrospective studies have reported that ICIs alone are effective in patients with LCNEC [11,[22][23][24][25][26][27]. However, in the tumor microenvironment (TME), the interaction between immune cells and nonimmune cells has led to the e cacy of ICIs not achieving the expected effect [21].…”

“…Studies have con rmed that the combination of surgery, chemotherapy, radiotherapy, targeted therapy, and other treatment modalities with ICIs can have a synergistic effect [28][29][30]. Currently, a limited number of studies [11,[22][23][24][25][26][27] have been published on the use of ICIs in patients with LCNEC; therefore, further research is needed to determine the appropriate treatment timing, treatment plan, and other in uencing factors. Based on the actual clinical applications and the complexity of TME, this study aimed to evaluate the clinical e cacy and safety of immunotherapy plus chemotherapy in patients with LCNEC.…”