Efficacy of immune check-point inhibitors (ICPi) in large cell neuroendocrine tumors of lung (LCNEC)

Sherman, Shira; Rotem, Ofer; Shochat, Tzippy; Zer, Alona; Moore, Assaf; Dudnik, Elizabeth

doi:10.1016/j.lungcan.2020.03.008

Cited by 39 publications

(47 citation statements)

References 34 publications

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“…The median PFS of 4.4 months and median OS of 11.4 months after ICI monotherapy in the current study were comparable with those in previous studies of ICI monotherapy in patients who mostly had cNSCLC (PFS, 2.3-4.0 months and OS, 9.2-13.8 months) [3][4][5][6]. In a retrospective study of 21 patients with LCNEC who received ICI monotherapy, median PFS and OS were 4.2 and 11.8 months, respectively [21]. In 49 patients with pulmonary pleomorphic carcinoma who received ICI monotherapy, median PFS and OS were 7.2 and 22.2 months, respectively [22].…”

Section: Discussionsupporting

confidence: 88%

Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer With Uncommon Histology: A Propensity-Score-Matched Analysis

Miyashita

Karayama

Inoue

et al. 2021

Preprint

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Background Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown. Methods Patients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: 1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and 2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups. Results Among a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8–7.7 months) and overall survival (OS) (11.4 months, 95 % CI 7.4–27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1–7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6–29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0–1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC. Conclusion ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.

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Section: Discussionsupporting

confidence: 88%

Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer With Uncommon Histology: A Propensity-Score-Matched Analysis

Miyashita

Karayama

Inoue

et al. 2021

Preprint

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“…Nevertheless, immunotherapy alone in SCLC did not provide the groundbreaking results obtained in NSCLC and we have few data regarding the role of immunotherapy in LCNECs [ 40 ]. Recently Sherman et al [ 41 ] reported an objective response rate of 33% and a median progression free survival of 4.9 months in a group of 37 consecutive LCNECs treated with immune check-point inhibitors and concluded that the outcomes are comparable with the outcomes reported in advanced NSCLC. Other studies are needed to validate these preliminary results, but for the purpose to select candidate LCNEC patients for immunotherapy, the classification of LCNEC in different genomic subtypes (i.e., “NSCLC-like” characterized by TP53 and KRAS / STK11 / KEAP1 , “SCLC-like” with concurrent TP53 and RB1 , and “Carcinoid-like” with MEN1 mutations) could play a very important role [ 23 ].…”

Section: Discussionmentioning

confidence: 96%

Beyond Traditional Morphological Characterization of Lung Neuroendocrine Neoplasms: In Silico Study of Next-Generation Sequencing Mutations Analysis across the Four World Health Organization Defined Groups

Centonze

Biganzoli

Prinzi

et al. 2020

Cancers

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Lung neuroendocrine neoplasms (LNENs) represent a rare and heterogeneous population of lung tumors. LNENs incidence rate has increased dramatically over the past 30 years. The current World Health Organization LNENs classification (WHO 2015), distinguished four LNENs prognostic categories, according to their morphology, necrosis amount and mitotic count: typical carcinoid (TC), atypical-carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC). At present, due to their rarity and biological heterogeneity there is still no consensus on the best therapeutic approach. Next-generation-sequencing analysis showed that WHO 2015 LNENs classes, could be characterized also by specific molecular alterations: frequently mutated genes involving chromatin remodeling and generally characterized by low mutational burden (MB) are frequently detected in both TC and AC; otherwise, TP53 and RB1 tumor suppressor genes alterations and high MB are usually detected in LCNEC and SCLC. We provide an overview concerning gene mutations in each WHO 2015 LNENs class in order to report the current LNENs mutational status as potential tool to better understand their clinical outcome and to drive medical treatment.

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“…LCNEC is a biologically heterogeneous group of tumors comprising distinct subsets based on genomic signatures: SCLC-like subset (TP53 + RB1 co-mutation/loss and other SCLC-type alterations), NSCLC-like subset (lack of co-altered TP53 + RB1 and a nearly universal occurrence of NSCLC-type mutations [STK11, KRAS, and KEAP1]), and carcinoid-like subset (MEN1 mutations and low mutation burden) 12 PD-1 inhibitors, such as pembrolizumab or nivolumab, are ICIs that are proven to improve overall survival in advanced NSCLC 13 14 ; however, data about the e cacy of ICIs in L-LCNEC are rare and limited mainly to some small sample clinical trials or a few case reports. Sherman et al analyzed 37 patients with advanced LCNEC and found that patients treated with ICIs had a longer median OS because advanced disease diagnosis was longer in patients treated with ICIs than those who were not 15 . In this context of limited data on the e cacy of ICIs in advanced LCNEC, little is known about their use in association with chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Complete tumor response in a patient with locally advanced lung large cell neuroendocrine carcinoma treated with Sintilimab plus platinum-based chemotherapy: a case report

Huang

Wang

et al. 2021

Preprint

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Background pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare subset of lung cancer with a poor prognosis. As LCNEC is an uncommon malignancy, the optimal treatment for LCNEC has not been established. Case presentation : we report a case of a 66-year-old man diagnosed with unresectable, locally advanced LCNEC who presented a partial radiographic response to immunotherapy combined with chemotherapy. Salvage surgery was performed after 4 cycles of docetaxel and cisplatin (DP) regimen plus sintilimab, which is a highly selective, fully human antiprogrammed death-ligand 1 monoclonal antibody. Moreover, a pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Conclusion this case suggests that patients with locally advanced LCNEC may benefit from neoadjuvant chemo-immunotherapy, it is worthy for further study.

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Efficacy of immune check-point inhibitors (ICPi) in large cell neuroendocrine tumors of lung (LCNEC)

Cited by 39 publications

References 34 publications

Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer With Uncommon Histology: A Propensity-Score-Matched Analysis

Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer With Uncommon Histology: A Propensity-Score-Matched Analysis

Beyond Traditional Morphological Characterization of Lung Neuroendocrine Neoplasms: In Silico Study of Next-Generation Sequencing Mutations Analysis across the Four World Health Organization Defined Groups

Complete tumor response in a patient with locally advanced lung large cell neuroendocrine carcinoma treated with Sintilimab plus platinum-based chemotherapy: a case report

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