TY - JOUR
T1 - INTEGRATE IIa Phase III Study
T2 - Regorafenib for Refractory Advanced Gastric Cancer
AU - Pavlakis, Nick
AU - Shitara, Kohei
AU - Sjoquist, Katrin
AU - Martin, Andrew
AU - Jaworski, Anthony
AU - Tebbutt, Niall
AU - Bang, Yung Jue
AU - Alcindor, Thierry
AU - O'Callaghan, Chris
AU - Strickland, Andrew
AU - Rha, Sun Young
AU - Lee, Keun Wook
AU - Kim, Jin Soo
AU - Bai, Li Yuan
AU - Hara, Hiroki
AU - Oh, Do Youn
AU - Yip, Sonia
AU - Zalcberg, John
AU - Price, Tim
AU - Simes, John
AU - Goldstein, David
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2025/2/1
Y1 - 2025/2/1
N2 - PURPOSE Treatment options for refractory advanced gastric and esophagogastric junction cancer (AGOC) are limited. Regorafenib, an oral multikinase inhibitor, prolonged progression-free survival (PFS) versus placebo in the INTEGRATE I phase II trial. INTEGRATE IIa was designed to examine whether regorafenib improved overall survival (OS).METHODSA double-blind placebo-controlled phase III trial compared regorafenib and best supportive care (BSC) versus placebo and BSC for participants with confirmed evaluable metastatic/advanced AGOC who failed ≥two prior therapies on a 2:1 random assignment, stratified by tumor location, geographic region (Asia v rest of world), and prior vascular endothelial growth factor inhibitors. The primary end point was OS. Treatment efficacy on OS was first tested in the pooled INTEGRATE I + INTEGRATE IIa cohort and, if significant, then in the INTEGRATE IIa cohort. Secondary end points were PFS, objective response rate, safety, and quality of life (QoL).RESULTSINTEGRATE IIa enrolled 251 participants: 157 from Asia and 94 from rest of world and 169 received regorafenib and 82 received placebo. No significant heterogeneity was observed between INTEGRATE I and INTEGRATE IIa studies on OS. Pooled OS analysis hazard ratio (HR) was 0.70 (95% CI, 0.56 to 0.87; P =.001; 361 events). INTEGRATE IIa alone OS HR was 0.68 (95% CI, 0.52 to 0.90; P =.006; 238 events), the median OS was 4.5 months versus 4.0 months, and 12-month survival rates were 19% and 6%, for regorafenib versus placebo, respectively. After a preplanned adjustment for multiplicity, there were no statistically significant differences across regions or other prespecified subgroups. Regorafenib improved PFS (HR, 0.53 [95% CI, 0.40 to 0.70]; P <.0001) and delayed deterioration in global QoL (HR, 0.68 [95% CI, 0.52 to 0.89]; P =.0043). The toxicity profile was consistent with that of previous reports.CONCLUSIONRegorafenib improves survival compared with placebo in refractory AGOC.
AB - PURPOSE Treatment options for refractory advanced gastric and esophagogastric junction cancer (AGOC) are limited. Regorafenib, an oral multikinase inhibitor, prolonged progression-free survival (PFS) versus placebo in the INTEGRATE I phase II trial. INTEGRATE IIa was designed to examine whether regorafenib improved overall survival (OS).METHODSA double-blind placebo-controlled phase III trial compared regorafenib and best supportive care (BSC) versus placebo and BSC for participants with confirmed evaluable metastatic/advanced AGOC who failed ≥two prior therapies on a 2:1 random assignment, stratified by tumor location, geographic region (Asia v rest of world), and prior vascular endothelial growth factor inhibitors. The primary end point was OS. Treatment efficacy on OS was first tested in the pooled INTEGRATE I + INTEGRATE IIa cohort and, if significant, then in the INTEGRATE IIa cohort. Secondary end points were PFS, objective response rate, safety, and quality of life (QoL).RESULTSINTEGRATE IIa enrolled 251 participants: 157 from Asia and 94 from rest of world and 169 received regorafenib and 82 received placebo. No significant heterogeneity was observed between INTEGRATE I and INTEGRATE IIa studies on OS. Pooled OS analysis hazard ratio (HR) was 0.70 (95% CI, 0.56 to 0.87; P =.001; 361 events). INTEGRATE IIa alone OS HR was 0.68 (95% CI, 0.52 to 0.90; P =.006; 238 events), the median OS was 4.5 months versus 4.0 months, and 12-month survival rates were 19% and 6%, for regorafenib versus placebo, respectively. After a preplanned adjustment for multiplicity, there were no statistically significant differences across regions or other prespecified subgroups. Regorafenib improved PFS (HR, 0.53 [95% CI, 0.40 to 0.70]; P <.0001) and delayed deterioration in global QoL (HR, 0.68 [95% CI, 0.52 to 0.89]; P =.0043). The toxicity profile was consistent with that of previous reports.CONCLUSIONRegorafenib improves survival compared with placebo in refractory AGOC.
UR - https://www.scopus.com/pages/publications/85206882695
U2 - 10.1200/JCO.24.00055
DO - 10.1200/JCO.24.00055
M3 - Article
C2 - 39365958
AN - SCOPUS:85206882695
SN - 0732-183X
VL - 43
SP - 453
EP - 463
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 4
ER -
