TY - JOUR
T1 - Efficacy and safety of maintenance therapy with pamiparib versus placebo for advanced gastric cancer responding to first-line platinum-based chemotherapy
T2 - Phase 2 study results
AU - Ciardiello, Fortunato
AU - Bang, Yung Jue
AU - Cervantes, Andrés
AU - Dvorkin, Mikhail
AU - Lopez, Charles D.
AU - Metges, Jean Philippe
AU - Sánchez Ruiz, Antonio
AU - Calvo, Mariona
AU - Strickland, Andrew H.
AU - Kannourakis, George
AU - Muro, Kei
AU - Kawakami, Hisato
AU - Wei, Jia
AU - Borg, Christophe
AU - Zhu, Zhaoyin
AU - Gupta, Neal
AU - Pelham, Robert J.
AU - Shen, Lin
N1 - Publisher Copyright:
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2023/6
Y1 - 2023/6
N2 - Background: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved for the treatment of various solid tumors. In gastric cancer, genes commonly harbor mutations in the homologous recombination DNA repair pathway, potentially increasing sensitivity to PARPi. Pamiparib (BGB-290) is a small molecule inhibitor of PARP1 and PARP2. Methods: The PARALLEL-303 study (NCT03427814) investigated the efficacy and safety of pamiparib 60 mg orally (PO) twice daily (BID) versus placebo PO BID as maintenance therapy in patients with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line chemotherapy. The primary endpoint of this double-blind, randomized, global phase 2 study was progression-free survival (PFS) (RECIST version 1.1; per investigator assessment). Secondary endpoints included overall survival (OS) and safety. Results: In total, 136 patients were randomized 1:1 to receive pamiparib (n = 71) or placebo (n = 65). Median PFS was numerically longer with pamiparib versus placebo but did not reach statistical significance (3.7 months [95% confidence interval (CI): 1.9, 5.3] vs. 2.1 months [95% CI: 1.9, 3.8]; hazard ratio 0.8 [95% CI: 0.5, 1.2]; p = 0.1428). Median OS was 10.2 months (95% CI: 8.7, 16.3) in the pamiparib arm versus 12.0 months (95% CI: 8.2, not estimable) in the placebo arm. Overall, 8 patients (11.3%) in the pamiparib arm and 2 patients (3.1%) in the placebo arm experienced ≥1 TEAE leading to treatment discontinuation. Conclusions: Maintenance pamiparib did not meet statistical significance for superiority versus placebo for PFS, but was well tolerated with few treatment discontinuations; no unexpected safety signals were identified.
AB - Background: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved for the treatment of various solid tumors. In gastric cancer, genes commonly harbor mutations in the homologous recombination DNA repair pathway, potentially increasing sensitivity to PARPi. Pamiparib (BGB-290) is a small molecule inhibitor of PARP1 and PARP2. Methods: The PARALLEL-303 study (NCT03427814) investigated the efficacy and safety of pamiparib 60 mg orally (PO) twice daily (BID) versus placebo PO BID as maintenance therapy in patients with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line chemotherapy. The primary endpoint of this double-blind, randomized, global phase 2 study was progression-free survival (PFS) (RECIST version 1.1; per investigator assessment). Secondary endpoints included overall survival (OS) and safety. Results: In total, 136 patients were randomized 1:1 to receive pamiparib (n = 71) or placebo (n = 65). Median PFS was numerically longer with pamiparib versus placebo but did not reach statistical significance (3.7 months [95% confidence interval (CI): 1.9, 5.3] vs. 2.1 months [95% CI: 1.9, 3.8]; hazard ratio 0.8 [95% CI: 0.5, 1.2]; p = 0.1428). Median OS was 10.2 months (95% CI: 8.7, 16.3) in the pamiparib arm versus 12.0 months (95% CI: 8.2, not estimable) in the placebo arm. Overall, 8 patients (11.3%) in the pamiparib arm and 2 patients (3.1%) in the placebo arm experienced ≥1 TEAE leading to treatment discontinuation. Conclusions: Maintenance pamiparib did not meet statistical significance for superiority versus placebo for PFS, but was well tolerated with few treatment discontinuations; no unexpected safety signals were identified.
KW - clinical trial
KW - gastric cancer
KW - maintenance
KW - phase 2
KW - poly(ADP-ribose) polymerase inhibitors
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U2 - 10.1002/cam4.5997
DO - 10.1002/cam4.5997
M3 - Article
C2 - 37260158
AN - SCOPUS:85161447559
SN - 2045-7634
VL - 12
SP - 13145
EP - 13154
JO - Cancer medicine
JF - Cancer medicine
IS - 12
ER -