TY - JOUR
T1 - Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer
AU - Shitara, Kohei
AU - Ajani, Jaffer A.
AU - Moehler, Markus
AU - Garrido, Marcelo
AU - Gallardo, Carlos
AU - Shen, Lin
AU - Yamaguchi, Kensei
AU - Wyrwicz, Lucjan
AU - Skoczylas, Tomasz
AU - Bragagnoli, Arinilda Campos
AU - Liu, Tianshu
AU - Tehfe, Mustapha
AU - Elimova, Elena
AU - Bruges, Ricardo
AU - Zander, Thomas
AU - de Azevedo, Sergio
AU - Kowalyszyn, Ruben
AU - Pazo-Cid, Roberto
AU - Schenker, Michael
AU - Cleary, James M.
AU - Yanez, Patricio
AU - Feeney, Kynan
AU - Karamouzis, Michalis V.
AU - Poulart, Valerie
AU - Lei, Ming
AU - Xiao, Hong
AU - Kondo, Kaoru
AU - Li, Mingshun
AU - Janjigian, Yelena Y.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/3/31
Y1 - 2022/3/31
N2 - Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma1–4. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries6. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively7–11. Treatment combining 1 mg kg−1 nivolumab with 3 mg kg−1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.
AB - Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma1–4. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries6. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively7–11. Treatment combining 1 mg kg−1 nivolumab with 3 mg kg−1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.
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U2 - 10.1038/s41586-022-04508-4
DO - 10.1038/s41586-022-04508-4
M3 - Article
C2 - 35322232
AN - SCOPUS:85126842255
SN - 0028-0836
VL - 603
SP - 942
EP - 948
JO - Nature
JF - Nature
IS - 7903
ER -