Kei Muro1, Jae Yong Cho2, Gyorgy Bodoky3, Chanchal Goswami4, Yee Chao5, Lucas V Dos Santos6, Yasuhiro Shimada7, Eldar Topuzov8, Eric Van Cutsem9, Josep Tabernero10, John Zalcberg11, Ian Chau12, Stefano Cascinu13, Rebecca Cheng14, Yanzhi Hsu15, Michael Emig16, Mauro Orlando17, Charles Fuchs18. 1. Aichi Cancer Center Hospital, Nagoya, Japan. 2. Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. 3. Szent László Hospital, Budapest, Hungary. 4. B.P. Poddar Hospital and Medical Research, Kolkata, West Bengal, India. 5. Taipei Veterans General Hospital, Taipei, Taiwan. 6. Beneficência Portuguesa, GI Unit Centro Oncológico Antônio Ermírio de Moraes, São Paulo, Brazil. 7. Kochi Health Sciences Center, Kochi, Japan. 8. Ministry of Healthcare of the Russian Federation, North-Western State Medical University n.a. I.I. Mechnikov, Saint Petersburg, Russia. 9. Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium. 10. Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain. 11. School of Public Health and Preventive Medicine, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia. 12. Royal Marsden Hospital, London and Surrey, UK. 13. Università di Modena e Reggio Emilia, Ancona, Italy. 14. Eli Lilly and Company, Taipei, Taiwan. 15. Eli Lilly and Company, Indianapolis, Indiana, USA. 16. Eli Lilly and Company, Bad Homburg, Germany. 17. Eli Lilly and Company, Buenos Aires, Argentina. 18. Yale Cancer Center, New Haven, Connecticut, USA.
Abstract
BACKGROUND AND AIM: REGARD and RAINBOW were global, phase 3, randomized, double-blind trials of second-line ramucirumab for metastatic gastric or gastroesophageal junction adenocarcinoma. Exploratory subgroup analyses were described to assess the efficacy and safety of ramucirumab in REGARD and RAINBOW in young (≤ 45 and < 65 years) and elderly (≥ 65, ≥ 70, and ≥ 75 years) patients. METHODS: Patients were randomized 2:1 to receive ramucirumab plus best supportive care or placebo plus best supportive care (REGARD) or 1:1 to ramucirumab plus paclitaxel or placebo plus paclitaxel (RAINBOW). Subpopulation Treatment Effect Pattern Plots assessed efficacy and adverse events by age groups for ramucirumab versus placebo. RESULTS: The hazard ratios (HRs) for overall survival favored treatment with ramucirumab: REGARD ≤ 45 years (HR: 0.59, 95% confidence interval: 0.27-1.26), < 65 years (0.80, 0.59-1.10), ≥ 65 years (0.72, 0.48-1.08), ≥ 70 years (0.73, 0.44-1.23), and ≥ 75 years (0.59, 0.25-1.37); and RAINBOW ≤ 45 years (0.56, 0.33-0.93), < 65 years (0.78, 0.63-0.97), ≥ 65 years (0.88, 0.66-1.18), and ≥ 70 years (0.88, 0.60-1.28). The exception was elderly patients aged ≥ 75 years in RAINBOW (0.97, 0.47-2.01); however, patient numbers were low in this subgroup (n = 36). Similar findings were observed for progression-free survival, for which HRs numerically favored ramucirumab-treated patients. Adverse events (including grade ≥ 3) were not associated with age. CONCLUSIONS: In comparison with placebo, ramucirumab conferred improvements in efficacy across age groups with a tolerable safety profile. Despite some limitations, these exploratory analyses support the use of ramucirumab in advanced gastric cancer, irrespective of age.
RCT Entities:
BACKGROUND AND AIM: REGARD and RAINBOW were global, phase 3, randomized, double-blind trials of second-line ramucirumab for metastatic gastric or gastroesophageal junction adenocarcinoma. Exploratory subgroup analyses were described to assess the efficacy and safety of ramucirumab in REGARD and RAINBOW in young (≤ 45 and < 65 years) and elderly (≥ 65, ≥ 70, and ≥ 75 years) patients. METHODS:Patients were randomized 2:1 to receive ramucirumab plus best supportive care or placebo plus best supportive care (REGARD) or 1:1 to ramucirumab plus paclitaxel or placebo plus paclitaxel (RAINBOW). Subpopulation Treatment Effect Pattern Plots assessed efficacy and adverse events by age groups for ramucirumab versus placebo. RESULTS: The hazard ratios (HRs) for overall survival favored treatment with ramucirumab: REGARD ≤ 45 years (HR: 0.59, 95% confidence interval: 0.27-1.26), < 65 years (0.80, 0.59-1.10), ≥ 65 years (0.72, 0.48-1.08), ≥ 70 years (0.73, 0.44-1.23), and ≥ 75 years (0.59, 0.25-1.37); and RAINBOW ≤ 45 years (0.56, 0.33-0.93), < 65 years (0.78, 0.63-0.97), ≥ 65 years (0.88, 0.66-1.18), and ≥ 70 years (0.88, 0.60-1.28). The exception was elderly patients aged ≥ 75 years in RAINBOW (0.97, 0.47-2.01); however, patient numbers were low in this subgroup (n = 36). Similar findings were observed for progression-free survival, for which HRs numerically favored ramucirumab-treated patients. Adverse events (including grade ≥ 3) were not associated with age. CONCLUSIONS: In comparison with placebo, ramucirumab conferred improvements in efficacy across age groups with a tolerable safety profile. Despite some limitations, these exploratory analyses support the use of ramucirumab in advanced gastric cancer, irrespective of age.
Authors: Kohei Shitara; Toshihiko Doi; Hisashi Hosaka; Peter Thuss-Patience; Armando Santoro; Federico Longo; Ozgur Ozyilkan; Irfan Cicin; David Park; Aziz Zaanan; Carles Pericay; Mustafa Özgüroğlu; Maria Alsina; Lukas Makris; Karim A Benhadji; David H Ilson Journal: Gastric Cancer Date: 2022-01-08 Impact factor: 7.701