Biagio Ricciuti1, Carlo Genova2, Maria Bassanelli3, Andrea De Giglio4, Marta Brambilla4, Giulio Metro4, Sara Baglivo4, Maria Giovanna Dal Bello2, Anna Ceribelli3, Francesco Grossi5, Rita Chiari4. 1. Medical Oncology, Thoracic Oncology Unit, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy. Electronic address: biagio.ricciuti@gmail.com. 2. Lung Cancer Unit, Ospedale Policlinico San Martino, Genova, Italia. 3. Medical Oncology, San Camillo de Lellis Hospital, Rieti, Italy. 4. Medical Oncology, Thoracic Oncology Unit, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy. 5. Lung Cancer Unit, Ospedale Policlinico San Martino, Genova, Italia; Division of Medical Oncology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
Abstract
INTRODUCTION: Treatment with immune checkpoint inhibitors beyond progression is associated with improved survival in patients with melanoma and clear-cell renal carcinoma. Whether this association exists for patients with non-small-cell lung cancer (NSCLC) is currently still unclear. PATIENTS AND METHODS: We performed a multi-institutional retrospective study based on landmark and multivariable analyses to evaluate the safety and efficacy of treatment with nivolumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression in patients with advanced NSCLC. Criteria for receiving nivolumab beyond progression were investigator-assessed clinical benefit, stable performance status, tolerance of treatment, and no need of immediate intervention to prevent serious complication of progression. RESULTS: Of 176 patients progressed to nivolumab according to RECIST v1.1, 60 (34.1%) were treated beyond progression (TBP) and 116 (65.9%) were not-TBP (NTBP). The median overall survival was significantly longer in the TBP group compared with the NTBP group (17.8 vs. 3.7 months; hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.21-0.46; P < .0001). In a landmark analysis of evaluable patients beginning 6 weeks from first progression, the median overall survival for patients TBP was 10.7 months and for those NTBP, 3.4 months (HR, 0.48; 95% CI, 0.30-0.77; P = .002). Discontinuation of nivolumab at first progression was associated with shorter survival in multivariable analysis (HR, 2.98; 95% CI, 1.95-4.54; P < .001). No safety concerns emerged in patients who were in the TBP group. CONCLUSION: A subset of patients with NSCLC and progressive disease may continue to benefit from nivolumab beyond progression. Discontinuation of immunotherapy based only on RECIST v1.1 may be premature.
INTRODUCTION: Treatment with immune checkpoint inhibitors beyond progression is associated with improved survival in patients with melanoma and clear-cell renal carcinoma. Whether this association exists for patients with non-small-cell lung cancer (NSCLC) is currently still unclear. PATIENTS AND METHODS: We performed a multi-institutional retrospective study based on landmark and multivariable analyses to evaluate the safety and efficacy of treatment with nivolumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression in patients with advanced NSCLC. Criteria for receiving nivolumab beyond progression were investigator-assessed clinical benefit, stable performance status, tolerance of treatment, and no need of immediate intervention to prevent serious complication of progression. RESULTS: Of 176 patients progressed to nivolumab according to RECIST v1.1, 60 (34.1%) were treated beyond progression (TBP) and 116 (65.9%) were not-TBP (NTBP). The median overall survival was significantly longer in the TBP group compared with the NTBP group (17.8 vs. 3.7 months; hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.21-0.46; P < .0001). In a landmark analysis of evaluable patients beginning 6 weeks from first progression, the median overall survival for patientsTBP was 10.7 months and for those NTBP, 3.4 months (HR, 0.48; 95% CI, 0.30-0.77; P = .002). Discontinuation of nivolumab at first progression was associated with shorter survival in multivariable analysis (HR, 2.98; 95% CI, 1.95-4.54; P < .001). No safety concerns emerged in patients who were in the TBP group. CONCLUSION: A subset of patients with NSCLC and progressive disease may continue to benefit from nivolumab beyond progression. Discontinuation of immunotherapy based only on RECIST v1.1 may be premature.
Authors: Giulio Metro; Alfredo Addeo; Diego Signorelli; Alessio Gili; Panagiota Economopoulou; Fausto Roila; Giuseppe Banna; Alessandro De Toma; Juliana Rey Cobo; Andrea Camerini; Athina Christopoulou; Giuseppe Lo Russo; Marco Banini; Domenico Galetta; Beatriz Jimenez; Ana Collazo-Lorduy; Antonio Calles; Panagiotis Baxevanos; Helena Linardou; Paris Kosmidis; Marina C Garassino; Giannis Mountzios Journal: J Thorac Dis Date: 2019-12 Impact factor: 2.895