Enrica Capelletto1, Maria Rita Migliorino2, Alessandro Morabito3, Rita Chiari4, Francesco Grossi5, Marcello Tiseo6, Francesco Di Costanzo7, Angelo Delmonte8, Gianpiero Romano9, Domenico Galetta10, Vieri Scotti11, Vanesa Gregorc12, Salvatore Pisconti13, Giovanni Luca Ceresoli14, Alessandro Del Conte15, Libero Ciuffreda16, Ida Colantonio17, Emilio Bria18, Serena Ricciardi2, Anna Manzo3, Giulio Metro4, Anna Maria Morelli19, Rossana Critelli19, Maria Vittoria Pacchiana19, Ilaria Stura20, Giuseppe Migliaretti20, Silvia Novello19. 1. Department of Oncology, University of Turin, AOU San Luigi, Orbassano, Italy. Electronic address: enrica.capelletto@gmail.com. 2. San Camillo Forlanini Hospital, UOSD Pneumologia Oncologica, Roma, Italy. 3. Thoracic Medical Oncology, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli Italy. 4. Santa Maria della Misericordia Hospital, Medical Oncology, Perugia Italy. 5. San Martino Hospital, Lung Cancer Unit, Genova Italy(1); Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano Italy(2). 6. Department of Medicine and Surgery, University of Parma, Parma Italy. 7. AOU Careggi, Medical Oncology, Firenze Italy. 8. Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) - IRCCS, Meldola Italy. 9. Vito Fazzi Hospital, UO Oncologia, Lecce Italy. 10. Clinical Cancer Center "Giovanni Paolo II", Thoracic Medical Oncology Unit, Bari Italy. 11. AOU Careggi, Radiation Oncology Unit - Oncology Department, Firenze Italy. 12. Department of Oncology, IRCCS San Raffaele, Milano Italy. 13. P.O.C.SS. Annunziata - S.G.Moscati, SC Oncologia Medica, Taranto Italy. 14. Humanitas Gavazzeni, Medical Oncology, Bergamo Italy. 15. Centro di Riferimento Oncologico (CRO) - IRCCS, Oncology Unit, Pordenone Italy. 16. A.O.U. Città della Salute e della Scienza di Torino - Presidio Molinette - SC Oncologia Medica I, Torino Italy. 17. S. Croce e Carle General Hospital, Medical Oncology, Cuneo Italy. 18. Department of Medicine, University of Verona, Oncology Unit,Verona Italy(1); Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma Italy(2). 19. Department of Oncology, University of Turin, AOU San Luigi, Orbassano, Italy. 20. Department of Public Health and Paediatric Sciences, University of Turin Italy.
Abstract
OBJECTIVES: Despite the scant docetaxel's tolerability, second-line association with nintedanib still represents a standard-of-care for non-squamous non-small cell lung cancer (nsNSCLC), giving to rapidly-progressing patients the greatest survival advantage. The SENECA trial is a phase IIb, open-label, study evaluating whether nintedanib/docetaxel can be equally effective and safe regardless docetaxel schedule. MATERIALS AND METHODS: Recurrent nsNSCLC patients were stratified into cohort 1 and 2, according to relapse-time (within or over 3 months) from end of first-line chemotherapy. They were treated with docetaxel (T1: 33 mg/mq on days 1 and 8 in a 21-days cycle; T2: 75 mg/mq q3wks) plus nintedanib, allowing maintenance in case of disease-control. Primary endpoint was progression-free survival (PFS) by investigator's assessment; secondary endpoints: overall survival (OS), safety and quality-of-life. RESULTS: Between January 2016-April 2018, 212 patients were evaluated: 30 resulted screening-failures, 12 were excluded for lack of compliance. According to investigator's choice, 85 patients received T1 docetaxel and 85 T2; 138 (81.2%) were stratified in C1, 32 (18.8%) in C2, with a median relapse-time of 0.54 and 9.29 months, respectively. Baseline characteristics were balanced between groups. After 35.5 months follow-up, no survival differences appear between cohorts and treatments; toxicity seems to be slightly higher in T2, especially for chemotherapy-related events. Perception of quality-of-life remains stable and docetaxel schedule doesn't modify patients' load. CONCLUSION: The SENECA trial confirms efficacy of second-line nintedanib/docetaxel for nsNSCLC, regardless time of recurrence and docetaxel schedule; higher toxicities for q3wks docetaxel, without alterations in quality-of-life, have been described, underling the possibility, adopting the weekly schedule, to maintain efficacy with better tolerability.
OBJECTIVES: Despite the scant docetaxel's tolerability, second-line association with nintedanib still represents a standard-of-care for non-squamous non-small cell lung cancer (nsNSCLC), giving to rapidly-progressing patients the greatest survival advantage. The SENECA trial is a phase IIb, open-label, study evaluating whether nintedanib/docetaxel can be equally effective and safe regardless docetaxel schedule. MATERIALS AND METHODS: Recurrent nsNSCLC patients were stratified into cohort 1 and 2, according to relapse-time (within or over 3 months) from end of first-line chemotherapy. They were treated with docetaxel (T1: 33 mg/mq on days 1 and 8 in a 21-days cycle; T2: 75 mg/mq q3wks) plus nintedanib, allowing maintenance in case of disease-control. Primary endpoint was progression-free survival (PFS) by investigator's assessment; secondary endpoints: overall survival (OS), safety and quality-of-life. RESULTS: Between January 2016-April 2018, 212 patients were evaluated: 30 resulted screening-failures, 12 were excluded for lack of compliance. According to investigator's choice, 85 patients received T1 docetaxel and 85 T2; 138 (81.2%) were stratified in C1, 32 (18.8%) in C2, with a median relapse-time of 0.54 and 9.29 months, respectively. Baseline characteristics were balanced between groups. After 35.5 months follow-up, no survival differences appear between cohorts and treatments; toxicity seems to be slightly higher in T2, especially for chemotherapy-related events. Perception of quality-of-life remains stable and docetaxel schedule doesn't modify patients' load. CONCLUSION: The SENECA trial confirms efficacy of second-line nintedanib/docetaxel for nsNSCLC, regardless time of recurrence and docetaxel schedule; higher toxicities for q3wks docetaxel, without alterations in quality-of-life, have been described, underling the possibility, adopting the weekly schedule, to maintain efficacy with better tolerability.
Authors: Virginia Campani; Iris Chiara Salaroglio; Valeria Nele; Joanna Kopecka; Andreas Bernkop-Schnürch; Chiara Riganti; Giuseppe De Rosa Journal: Pharmaceutics Date: 2022-01-26 Impact factor: 6.321