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Comparative Study
. 2021 Feb;9(2):e001999.
doi: 10.1136/jitc-2020-001999.

Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung

Elizabeth Dudnik #  1   2 , Samuel Kareff #  3 , Mor Moskovitz  4 , Chul Kim  3 , Stephen V Liu  3 , Anastasiya Lobachov  5 , Teodor Gottfried  5 , Damien Urban  5 , Alona Zer  6   2 , Ofer Rotem  6 , Amir Onn  2   7 , Mira Wollner  4 , Jair Bar  2   5 ; Israel Lung Cancer Group
Affiliations
Comparative Study

Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung

Elizabeth Dudnik et al. J Immunother Cancer. 2021 Feb.

Abstract

Background: Little is known regarding the efficacy of immune checkpoint inhibitors (ICI) in patients with advanced large-cell neuroendocrine lung carcinoma (aLCNEC).

Methods: 125 consecutive patients with aLCNEC were identified in the electronic databases of 4 participating cancer centers. The patients were divided into group A (patients who received ICI, n=41) and group B (patients who did not receive ICI, n=84). Overall survival since advanced disease diagnosis (OS DX) and OS since ICI initiation (OS ICI) were captured.

Results: With a median follow-up of 11.8 months (mo) (IQR 7.5-17.9) and 6.0mo (IQR 3.1-10.9), 66% and 76% of patients died in groups A and B, respectively. Median OS DX was 12.4mo (95% CI 10.7 to 23.4) and 6.0mo (95% CI 4.7 to 9.4) in groups A and B, respectively (log-rank test, p=0.02). For ICI administration, HR for OS DX was 0.59 (95% CI 0.38 to 0.93, p=0.02-unadjusted), and 0.58 (95% CI 0.34 to 0.98, p=0.04-adjusted for age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), presence of liver metastases and chemotherapy administration). In a propensity score matching analysis (n=74; 37 patients in each group matched for age and ECOG PS), median OS DX was 12.5 mo (95% CI 10.6 to 25.2) and 8.4 mo (95% CI 5.4 to 16.9) in matched groups A and B, respectively (log-rank test, p=0.046). OS ICI for patients receiving ICI as monotherapy (n=36) was 11.0 mo (95% CI 6.1 to 19.4).

Conclusions: With the limitations of retrospective design and small sample size, the results of this real-world cohort analysis suggest a positive impact of ICI on OS in aLCNEC.

Keywords: active; immunotherapy; lung neoplasms; programmed cell death 1 receptor.

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Conflict of interest statement

Competing interests: ED reported consulting fees from MSD, BMS, Astra Zeneca, Roche, Boehringer Ingelheim, Pfizer, Novartis, Takeda. MM reported consulting fees from Boehringer Ingelheim, Roche, Astra Zeneca, MSD, BMS, Abbvie, Takeda, Pomicell. CK reported research funding (to institution) from AstraZeneca, BMS, Novartis, Regeneron, Tesaro, Karyopharm, Debiopharm, Jassen, and Mirati and consulting fees from Novartis. SVL reported consulting fees from AstraZeneca, Beigene, Blueprint, Boehringer Ingelheim, Bristol-Myers Squibb, Catalyst, Celgene, Clovis, Corvus, G1 Therapeutics, Genentech, Guardant Health, Inivata, Janssen, Jazz, Lilly, LOXO, MSD, PharmaMar, Pfizer, Regeneron, and Takeda and research grants (to institution) from Alkermes, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Genentech, Lilly, Lycera, Merck, Molecular Partners, Pfizer, Rain Therapeutics, RAPT, Spectrum, and Turning Point Therapeutics. DU reported consulting fees and non-financial support from BMS, Astra Zeneca, Takeda, consulting fees MSD, Roche and Boehringer Ingelheim. AZ reported grants from BMS, personal fees from Roche, MSD, BMS, Astra Zeneca, Takeda. AO reported advisory fees from MSD, BMS, Roche, Astra Zeneca, Novartis, Boehringer Ingelheim. MW reported speaker fees and funding (to institution) from Roche, MSD. JB reported grants and personal fees from MSD, Roche, BMS, Abbvie, Pfizer, Novartis, Astra Zeneca, Boehringer Ingelheim, Takeda.

Figures

Figure 1
Figure 1
OS of patients with advanced LCNEC according to ICI exposure in the entire cohort (A, n=125), and in the cohort matched for age and ECOG PS (B, n-74): group A—patients who received ICI; group B—patients who did not receive ICI. ECOG PS, Eastern Cooperative Oncology Group performance status score; ICI, immune check point inhibitors; LCNEC, large-cell neuroendocrine tumors of lung; mOS, median overall survival.
Figure 2
Figure 2
The effect of ICI exposure on OS of patients with advanced LCNEC in selected subgroups according to age (A1 ≥65 years; A2 ≤65 years), ECOG PS (B1-ECOG PS 0/1; B2-ECOG PS 2–4), liver metastases (C1-liver metastases present; C2-liver metastases absent) and molecular subtype (D1-SCLC-like subtype or unknown molecular subtype; D2-NSCLC-like subtype). ECOG PS, Eastern Cooperative Oncology Group performance status score; ICI, immune checkpoint inhibitors; LCNEC, large-cell neuroendocrine tumors of lung; mOS, median overall survival; NR, not reached; NSCLC, non-small-cell lung cancer; SCLC, small-cell lung cancer.
Figure 3
Figure 3
OS with ICI in patients with advanced LCNEC. ICI, immune checkpoint inhibitors; LCNEC, large-cell neuroendocrine tumors of lung; mOS, median overall survival.
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References

    1. Derks JL, Hendriks LE, Buikhuisen WA, et al. . Clinical features of large cell neuroendocrine carcinoma: a population-based overview. Eur Respir J 2016;47:615–24. 10.1183/13993003.00618-2015 - DOI - PubMed
    1. Lo Russo G, Pusceddu S, Proto C, et al. . Treatment of lung large cell neuroendocrine carcinoma. Tumour Biol 2016;37:7047–57. 10.1007/s13277-016-5003-4 - DOI - PubMed
    1. Kinoshita T, Yoshida J, Ishii G, et al. . The differences of biological behavior based on the clinicopathological data between resectable large-cell neuroendocrine carcinoma and small-cell lung carcinoma. Clin Lung Cancer 2013;14:535–40. 10.1016/j.cllc.2013.04.003 - DOI - PubMed
    1. Travis WD, Brambilla E, Nicholson AG, et al. . The 2015 World Health organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 2015;10:1243–60. 10.1097/JTO.0000000000000630 - DOI - PubMed
    1. Rekhtman N, Pietanza MC, Hellmann MD, et al. . Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma-like and non-small cell carcinoma-like subsets. Clin Cancer Res 2016;22:3618–29. 10.1158/1078-0432.CCR-15-2946 - DOI - PMC - PubMed

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