Fausto Petrelli1, Alessandro Inno2, Antonio Ghidini3, Stefania Gori2, Melissa Bersanelli4. 1. Oncology Unit, Medical Sciences Department, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy. faupe@libero.it. 2. Oncology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy. 3. Oncology Unit, Casa di Cura Igea, Milan, Italy. 4. Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Abstract
INTRODUCTION: Immune checkpoint inhibitors (ICIs) represent a cornerstone for the treatment of many advanced tumors. When 65 is considered as a cut-off age, ICIs are equally effective in younger and older patients. However, the efficacy of ICIs among patients aged ≥ 75 remains uncertain, since those patients were generally under-represented in clinical trials. We performed a pooled analysis of major randomized trials including data of outcome in very older population. MATERIAL AND METHODS: We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials published from the inception of each database to November 22th, 2019. We only included (1) randomized studies comparing ICIs alone or in combinations with no ICIs, (2) studies reporting data of patients older than 75 years, (3) studies for solid tumors, and (4) studies with HR and 95% confidence interval (CI) available for OS based on 75 years as cut-off age. All data were expressed as the combination of HR and 95% CI, and P < 0.05 was considered to be statistically significant. RESULTS: A total of n = 8 publications for a total of n = 12 randomized studies were aggregated in the quantitative analysis. Overall, the pooled analysis showed a borderline significant OS benefit for ICIs compared to no ICIs arms (HR = 0.84, 95% CI 0.7-1; P = 0.05) in particular in first-line trials with HR = 0.77 (95%CI 0.61-0.96; P = 0.02). CONCLUSION: We conclude that ICIs may be offered in patients older than 75 years, providing a complete geriatric and clinical evaluation is performed in all subjects before starting therapy.
INTRODUCTION: Immune checkpoint inhibitors (ICIs) represent a cornerstone for the treatment of many advanced tumors. When 65 is considered as a cut-off age, ICIs are equally effective in younger and older patients. However, the efficacy of ICIs among patients aged ≥ 75 remains uncertain, since those patients were generally under-represented in clinical trials. We performed a pooled analysis of major randomized trials including data of outcome in very older population. MATERIAL AND METHODS: We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials published from the inception of each database to November 22th, 2019. We only included (1) randomized studies comparing ICIs alone or in combinations with no ICIs, (2) studies reporting data of patients older than 75 years, (3) studies for solid tumors, and (4) studies with HR and 95% confidence interval (CI) available for OS based on 75 years as cut-off age. All data were expressed as the combination of HR and 95% CI, and P < 0.05 was considered to be statistically significant. RESULTS: A total of n = 8 publications for a total of n = 12 randomized studies were aggregated in the quantitative analysis. Overall, the pooled analysis showed a borderline significant OS benefit for ICIs compared to no ICIs arms (HR = 0.84, 95% CI 0.7-1; P = 0.05) in particular in first-line trials with HR = 0.77 (95%CI 0.61-0.96; P = 0.02). CONCLUSION: We conclude that ICIs may be offered in patients older than 75 years, providing a complete geriatric and clinical evaluation is performed in all subjects before starting therapy.
Authors: Caroline Robert; Georgina V Long; Benjamin Brady; Caroline Dutriaux; Michele Maio; Laurent Mortier; Jessica C Hassel; Piotr Rutkowski; Catriona McNeil; Ewa Kalinka-Warzocha; Kerry J Savage; Micaela M Hernberg; Celeste Lebbé; Julie Charles; Catalin Mihalcioiu; Vanna Chiarion-Sileni; Cornelia Mauch; Francesco Cognetti; Ana Arance; Henrik Schmidt; Dirk Schadendorf; Helen Gogas; Lotta Lundgren-Eriksson; Christine Horak; Brian Sharkey; Ian M Waxman; Victoria Atkinson; Paolo A Ascierto Journal: N Engl J Med Date: 2014-11-16 Impact factor: 91.245
Authors: Toni K Choueiri; Bernard Escudier; Thomas Powles; Paul N Mainwaring; Brian I Rini; Frede Donskov; Hans Hammers; Thomas E Hutson; Jae-Lyun Lee; Katriina Peltola; Bruce J Roth; Georg A Bjarnason; Lajos Géczi; Bhumsuk Keam; Pablo Maroto; Daniel Y C Heng; Manuela Schmidinger; Philip W Kantoff; Anne Borgman-Hagey; Colin Hessel; Christian Scheffold; Gisela M Schwab; Nizar M Tannir; Robert J Motzer Journal: N Engl J Med Date: 2015-09-25 Impact factor: 91.245
Authors: Julie Brahmer; Karen L Reckamp; Paul Baas; Lucio Crinò; Wilfried E E Eberhardt; Elena Poddubskaya; Scott Antonia; Adam Pluzanski; Everett E Vokes; Esther Holgado; David Waterhouse; Neal Ready; Justin Gainor; Osvaldo Arén Frontera; Libor Havel; Martin Steins; Marina C Garassino; Joachim G Aerts; Manuel Domine; Luis Paz-Ares; Martin Reck; Christine Baudelet; Christopher T Harbison; Brian Lestini; David R Spigel Journal: N Engl J Med Date: 2015-05-31 Impact factor: 91.245
Authors: Ramaswamy Govindan; Aleksandra Szczesna; Myung-Ju Ahn; Claus-Peter Schneider; Pablo Fernando Gonzalez Mella; Fabrice Barlesi; Baohui Han; Doina Elena Ganea; Joachim Von Pawel; Vladimir Vladimirov; Natalia Fadeeva; Ki Hyeong Lee; Takayasu Kurata; Li Zhang; Tomohide Tamura; Pieter E Postmus; Jacek Jassem; Kenneth O'Byrne; Justin Kopit; Mingshun Li; Marina Tschaika; Martin Reck Journal: J Clin Oncol Date: 2017-08-30 Impact factor: 44.544
Authors: Martin Reck; Alexander Luft; Aleksandra Szczesna; Libor Havel; Sang-We Kim; Wallace Akerley; Maria Catherine Pietanza; Yi-Long Wu; Christoph Zielinski; Michael Thomas; Enriqueta Felip; Kathryn Gold; Leora Horn; Joachim Aerts; Kazuhiko Nakagawa; Paul Lorigan; Anne Pieters; Teresa Kong Sanchez; Justin Fairchild; David Spigel Journal: J Clin Oncol Date: 2016-11-01 Impact factor: 44.544
Authors: Matthew D Hellmann; Luis Paz-Ares; Reyes Bernabe Caro; Bogdan Zurawski; Sang-We Kim; Enric Carcereny Costa; Keunchil Park; Aurelia Alexandru; Lorena Lupinacci; Emmanuel de la Mora Jimenez; Hiroshi Sakai; Istvan Albert; Alain Vergnenegre; Solange Peters; Konstantinos Syrigos; Fabrice Barlesi; Martin Reck; Hossein Borghaei; Julie R Brahmer; Kenneth J O'Byrne; William J Geese; Prabhu Bhagavatheeswaran; Sridhar K Rabindran; Ravi S Kasinathan; Faith E Nathan; Suresh S Ramalingam Journal: N Engl J Med Date: 2019-09-28 Impact factor: 91.245