Melissa Bersanelli1, Sebastiano Buti2, Diana Giannarelli3, Alessandro Leonetti4, Alessio Cortellini5, Giuseppe Lo Russo6, Diego Signorelli6, Luca Toschi7, Michele Milella8, Sara Pilotto8, Emilio Bria9, Claudia Proto6, Arianna Marinello7, Giovanni Randon6, Sabrina Rossi7, Emanuele Vita9, Giulia Sartori8, Ettore D'Argento9, Eva Qako10, Elisa Giaiacopi10, Laura Ghilardi11, Anna Cecilia Bettini11, Elena Rapacchi2, Francesca Mazzoni12, Daniele Lavacchi12, Vieri Scotti13, Lucia Pia Ciccone13, Michele De Tursi14, Pietro Di Marino14, Daniele Santini15, Marco Russano15, Paola Bordi2, Massimo Di Maio16, Marco Audisio16, Marco Filetti17, Raffaele Giusti17, Rossana Berardi18, Ilaria Fiordoliva18, Giulio Cerea19, Elio Gregory Pizzutilo19, Alessandra Bearz20, Elisa De Carlo20, Fabiana Cecere21, Davide Renna21, Roberta Camisa2, Giuseppe Caruso2, Corrado Ficorella5, Giuseppe Luigi Banna22, Diego Cortinovis23, Matteo Brighenti24, Marina Chiara Garassino6, Marcello Tiseo4. 1. Medicine and Surgery Department, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy. Electronic address: bersamel@libero.it. 2. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 3. Regina Elena National Cancer Institute, IRCCS, Biostatistical Unit, Roma, Italy. 4. Medicine and Surgery Department, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 5. Department of Biotechnology and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy; Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy. 6. Oncologia Toracica, Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy. 7. Medical Oncology, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milano, Italy. 8. Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy. 9. Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, and Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy. 10. Medicine and Surgery Department, University of Parma, Parma, Italy. 11. UO di Oncologia medica, ASST PAPA Giovanni XXIII Bergamo, Italy. 12. Oncology Department, Careggi University Hospital, Firenze, Italy. 13. Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy. 14. Dipartimento di Scienze mediche, orali e biotecnologiche, Sezione di Oncologia, Università G. D'Annunzio, Chieti, Italy. 15. Oncologia Medica, Università Campus Bio-Medico, Roma, Italy. 16. Department of Oncology, University of Turin, AO Ordine Mauriziano Hospital, Torino, Italy. 17. Medical Oncology Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, Roma, Italy. 18. Clinica Oncologica, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy. 19. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy. 20. Centro di Riferimento Oncologico, CRO-IRCCS, Aviano, Italy. 21. Regina Elena National Cancer Institute, IRCCS, Oncology Unit, Roma, Italy. 22. Portsmouth Hospitals NHS Trust, Portsmouth, UK. 23. SC Oncologia/SS Lung Unit Asst H S Gerardo, Monza, Italy. 24. Medical Oncology Department, ASST Cremona, Cremona, Italy.
Abstract
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.
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 NSCLCpatients. MATERIALS AND METHODS: We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLCpatients 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 NSCLCpatients, 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.
Authors: Tian Tian; Min Yu; Yang Yu; Ke Wang; Panwen Tian; Ziyue Luo; Zhenyu Ding; Ye Wang; Youling Gong; Jiang Zhu; Bingwen Zou; Terence T Sio; Adelaide Alves; Yongmei Liu; Meijuan Huang; You Lu Journal: Transl Lung Cancer Res Date: 2022-06