TY - JOUR
T1 - Rivoceranib, a VEGFR-2 inhibitor, monotherapy in previously treated patients with advanced or metastatic gastric or gastroesophageal junction cancer (ANGEL study)
T2 - an international, randomized, placebo-controlled, phase 3 trial
AU - Kang, Yoon Koo
AU - Ryu, Min Hee
AU - Di Bartolomeo, Maria
AU - Chau, Ian
AU - Yoon, Harry
AU - Kim, Jong Gwang
AU - Lee, Keun Wook
AU - Oh, Sang Chul
AU - Takashima, Atsuo
AU - Kryzhanivska, Anna
AU - Chao, Yee
AU - Evesque, Ludovic
AU - Schenker, Michael
AU - McGinn, Arlo
AU - Zhao, Yufan
AU - Lee, Jennifer
AU - Wyrwicz, Lucjan
AU - Boku, Narikazu
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/3
Y1 - 2024/3
N2 - Background: Rivoceranib is an oral, selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. ANGEL (NCT03042611) was a global, randomized, double-blinded, placebo-controlled, phase 3 study evaluating rivoceranib as 3rd-line or ≥4th-line therapy in patients with advanced/metastatic gastric or gastroesophageal junction (GEJ) cancer. Methods: Patients had failed ≥2 lines of chemotherapy and were randomized 2:1 to rivoceranib 700 mg once daily or placebo with best supportive care. Primary endpoint: overall survival (OS) in the intention-to-treat population. Secondary endpoints: progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by blinded independent central review (BICR). Results: In total, 460 patients (rivoceranib n = 308, placebo n = 152) were enrolled. OS was not statistically different for rivoceranib versus placebo (median 5.78 vs. 5.13 months; hazard ratio [HR] 0.93, 95% CI 0.74–1.15; p = 0.4724). PFS by BICR (median 2.83 vs. 1.77 months; HR 0.58, 95% CI 0.47–0.71; p < 0.0001), ORR (6.5% vs. 1.3%; p = 0.0119), and DCR (40.3 vs. 13.2%; p < 0.0001) were improved with rivoceranib versus placebo. In patients receiving ≥4th-line therapy, OS (median 6.34 vs. 4.73 months; p = 0.0192) and PFS by BICR (median 3.52 vs. 1.71 months; p < 0.0001) were improved with rivoceranib versus placebo. The most common grade ≥ 3 treatment-emergent adverse events with rivoceranib were hypertension (17.9%), anemia (10.4%), aspartate aminotransferase increased (9.4%), asthenia (8.5%), and proteinuria (7.5%). Conclusions: This study did not meet its primary OS endpoint. Compared to placebo, rivoceranib improved PFS, ORR, and DCR. Rivoceranib also improved OS in a prespecified patient subgroup receiving ≥4th-line therapy.
AB - Background: Rivoceranib is an oral, selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. ANGEL (NCT03042611) was a global, randomized, double-blinded, placebo-controlled, phase 3 study evaluating rivoceranib as 3rd-line or ≥4th-line therapy in patients with advanced/metastatic gastric or gastroesophageal junction (GEJ) cancer. Methods: Patients had failed ≥2 lines of chemotherapy and were randomized 2:1 to rivoceranib 700 mg once daily or placebo with best supportive care. Primary endpoint: overall survival (OS) in the intention-to-treat population. Secondary endpoints: progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by blinded independent central review (BICR). Results: In total, 460 patients (rivoceranib n = 308, placebo n = 152) were enrolled. OS was not statistically different for rivoceranib versus placebo (median 5.78 vs. 5.13 months; hazard ratio [HR] 0.93, 95% CI 0.74–1.15; p = 0.4724). PFS by BICR (median 2.83 vs. 1.77 months; HR 0.58, 95% CI 0.47–0.71; p < 0.0001), ORR (6.5% vs. 1.3%; p = 0.0119), and DCR (40.3 vs. 13.2%; p < 0.0001) were improved with rivoceranib versus placebo. In patients receiving ≥4th-line therapy, OS (median 6.34 vs. 4.73 months; p = 0.0192) and PFS by BICR (median 3.52 vs. 1.71 months; p < 0.0001) were improved with rivoceranib versus placebo. The most common grade ≥ 3 treatment-emergent adverse events with rivoceranib were hypertension (17.9%), anemia (10.4%), aspartate aminotransferase increased (9.4%), asthenia (8.5%), and proteinuria (7.5%). Conclusions: This study did not meet its primary OS endpoint. Compared to placebo, rivoceranib improved PFS, ORR, and DCR. Rivoceranib also improved OS in a prespecified patient subgroup receiving ≥4th-line therapy.
KW - Stomach neoplasms
KW - Tyrosine protein kinase inhibitors
KW - Vascular endothelial growth factor receptor-2
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U2 - 10.1007/s10120-023-01455-5
DO - 10.1007/s10120-023-01455-5
M3 - Article
C2 - 38281295
AN - SCOPUS:85183367348
SN - 1436-3291
VL - 27
SP - 375
EP - 386
JO - Gastric Cancer
JF - Gastric Cancer
IS - 2
ER -