TY - JOUR
T1 - Chemotherapy in non-small cell lung cancer patients after prior immunotherapy
T2 - The multicenter retrospective CLARITY study
AU - study, CLARITY
AU - Bersanelli, Melissa
AU - Buti, Sebastiano
AU - Giannarelli, Diana
AU - Leonetti, Alessandro
AU - Cortellini, Alessio
AU - Russo, Giuseppe Lo
AU - Signorelli, Diego
AU - Toschi, Luca
AU - Milella, Michele
AU - Pilotto, Sara
AU - Bria, Emilio
AU - Proto, Claudia
AU - Marinello, Arianna
AU - Randon, Giovanni
AU - Rossi, Sabrina
AU - Vita, Emanuele
AU - Sartori, Giulia
AU - D'Argento, Ettore
AU - Qako, Eva
AU - Giaiacopi, Elisa
AU - Ghilardi, Laura
AU - Bettini, Anna Cecilia
AU - Rapacchi, Elena
AU - Mazzoni, Francesca
AU - Lavacchi, Daniele
AU - Scotti, Vieri
AU - Ciccone, Lucia Pia
AU - De Tursi, Michele
AU - Di Marino, Pietro
AU - Santini, Daniele
AU - Russano, Marco
AU - Bordi, Paola
AU - Di Maio, Massimo
AU - Audisio, Marco
AU - Filetti, Marco
AU - Giusti, Raffaele
AU - Berardi, Rossana
AU - Fiordoliva, Ilaria
AU - Cerea, Giulio
AU - Pizzutilo, Elio Gregory
AU - Bearz, Alessandra
AU - De Carlo, Elisa
AU - Cecere, Fabiana
AU - Renna, Davide
AU - Camisa, Roberta
AU - Caruso, Giuseppe
AU - Ficorella, Corrado
AU - Banna, Giuseppe Luigi
AU - Cortinovis, Diego
AU - Garassino, Marina Chiara
N1 - Funding Information: Melissa Bersanelli received funding outside the present study by Seqirus and Roche S.p.A . (FICOG as Institution, no personal fees), research funding from Pfizer and Novartis (University as Institution) , honoraria as speaker at scientific events (personal fees) by Astra Zeneca, Bristol-Myers Squibb (BMS), Novartis and Pfizer ; personal fees as consultant for advisory role by Novartis, BMS and Pfizer. Massimo Di Maio reports personal fees from Bristol Myers Squibb , personal fees from Merck Sharp & Dohme , personal fees from AstraZeneca , personal fees from Janssen , personal fees from Astellas , personal fees from Pfizer , personal fees from Eisai , personal fees from Takeda , grants from Tesaro GSK , outside the submitted work. Raffaele Giusti declared Advisory boards/Honoraria/Speakers’ fee/Consultant for: Astra Zeneca, Roche. Sebastiano Buti received honoraria as speaker at scientific events and advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli-Lilly, AstraZeneca and Novartis; he also received research funding from Novartis . Marcello Tiseo received honoraria (personal fees) by MSD, BMS, Boehringer (BI), Takeda, AstraZeneca , and research funding by AstraZeneca (Institution) . Vieri Scotti participated, with personal fees, to advisory boards and speaker's bureaus for Roche S.p.A. Rossana Berardi declared institutional grants from AZ, BI, Otsuka, Lilly, Novartis, MSD . Alessio Cortellini reports grants from AstraZeneca , grants from MSD , grants from BMS , grants from Roche , during the conduct of the study; grants from AstraZeneca , grants from MSD , grants from BMS , grants from Roche , grants from Novartis , outside the submitted work. Saverio Cinieri declared international board for Eli Lilly international. Sara Pilotto reports personal fees from AstraZeneca, Eli Lilly, Boehringer Ingelheim, Merk & Co, Roche , outside the submitted work. Dr. Garassino reports grants and personal fees from Eli Lilly , personal fees from Boehringer Ingelheim , grants and personal fees from Otsuka Pharma , grants and personal fees from Astra Zeneca , grants and personal fees from Novartis , grants and personal fees from BMS , grants and personal fees from Roche , grants and personal fees from Pfizer , grants and personal fees from Celgene , grants and personal fees from Incyte , personal fees from Inivata , personal fees from Takeda , grants from Tiziana Sciences , grants from Clovis , grants from Merck Serono , grants and personal fees from Bayer , grants and personal fees from MSD , grants and personal fees from GlaxoSmithKline S.p.A. , personal fees from Sanofi-Aventis , grants and personal fees from Spectrum Pharmaceutcials , grants and personal fees from Blueprint Medicine , personal fees from Seattle Genetics , personal fees from Daiichi Sankyo , grants from UNITED THERAPEUTICS CORPORATION , grants from Merck KGaA , personal fees from Jannesen , non-financial support from MSD, non-financial support from Pfizer, non-financial support from Eli-Lilly, grants from TURNING POINT , grants from IPSEN , grants from MedImmune , grants from EXELISIS , outside the submitted work. Giuseppe Lo Russo declares personal fees from AstraZeneca, MSD , outside the submitted work and travel accommodation with Roche and BMS. Diego Signorelli declares personal fees from AstraZeneca, Boehringer Ingelheim and BMS , outside the submitted work. Claudia Proto declares personal fees from BMS and MSD , outside the submitted work. Francesca Mazzoni declared grants by Takeda, MSD e Roche . Emilio Bria received speakers’ and travels’ fee from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche , and consultant’s fee from Roche, Pfizer ; he also received institutional research grants from AstraZeneca, Roche , and he is currently supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) under Investigator Grant (IG) No. IG20583 , and Institutional funds of Università Cattolica del Sacro Cuore (UCSC-project D1-2018/2019 ). Alessandro Leonetti declares speaker's fees for AstraZeneca . Luca Toschi declared advisory board for MSD; speaker fees for BMS and Roche. Michele Milella reports personal fees from Pfizer, EUSA Pharma and Astra Zeneca , outside the submitted manuscript. All the other authors have no conflict of interest to declare. Publisher Copyright: © 2020 Elsevier B.V. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Objectives: In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of “druggable” mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients. Materials and Methods: We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019. The primary endpoint of the study was represented by overall survival (OS), defined as the time from CT initiation to death. Secondary outcome endpoints of the SCAI (progression free survival, PFS, objective response rate, ORR and toxicity) and explorative biomarkers (lactate dehydrogenase, LDH, and neutrophil-to-lymphocyte ratio, NLR during immunotherapy) were also analyzed. Results: In our study population of 342 NSCLC patients, SCAI obtained a median OS of 6.8 months (95 % confidence interval, CI 5.5–8.1), median PFS of 4.1 months (95 % CI 3.4−4.8) and ORR of 22.8 %. A “Post-CKI score” was constructed by combining significant predictors of OS at the multivariate analyses (sex, ECOG PS, disease control with prior immunotherapy), Harrell'C was 0.65, (95 % CI:0.59−0.71). Conclusions: Despite the late-line settings, our findings support the hypothesis that previous immunotherapy might increase the sensitivity of the tumor to the subsequent chemotherapy. The “Post-CKI score” was clinically effective in successfully discriminating three distinct prognostic subgroups of patients after the failure of CKI, representing a possibly useful tool for the tailored decision-making process of advanced treatment-line settings in NSCLC.
AB - Objectives: In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of “druggable” mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients. Materials and Methods: We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019. The primary endpoint of the study was represented by overall survival (OS), defined as the time from CT initiation to death. Secondary outcome endpoints of the SCAI (progression free survival, PFS, objective response rate, ORR and toxicity) and explorative biomarkers (lactate dehydrogenase, LDH, and neutrophil-to-lymphocyte ratio, NLR during immunotherapy) were also analyzed. Results: In our study population of 342 NSCLC patients, SCAI obtained a median OS of 6.8 months (95 % confidence interval, CI 5.5–8.1), median PFS of 4.1 months (95 % CI 3.4−4.8) and ORR of 22.8 %. A “Post-CKI score” was constructed by combining significant predictors of OS at the multivariate analyses (sex, ECOG PS, disease control with prior immunotherapy), Harrell'C was 0.65, (95 % CI:0.59−0.71). Conclusions: Despite the late-line settings, our findings support the hypothesis that previous immunotherapy might increase the sensitivity of the tumor to the subsequent chemotherapy. The “Post-CKI score” was clinically effective in successfully discriminating three distinct prognostic subgroups of patients after the failure of CKI, representing a possibly useful tool for the tailored decision-making process of advanced treatment-line settings in NSCLC.
KW - Chemotherapy after immunotherapy
KW - CLARITY
KW - Immune checkpoint inhibitors
KW - NSCLC
KW - Salvage chemotherapy
U2 - 10.1016/j.lungcan.2020.10.008
DO - 10.1016/j.lungcan.2020.10.008
M3 - Article
VL - 150
SP - 123
EP - 131
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
ER -