Efficacy and safety of maintenance therapy with pamiparib versus placebo for advanced gastric cancer responding to first-line platinum-based chemotherapy: Phase 2 study results
Por:
Ciardiello F, Bang Y, Cervantes A, Dvorkin M, Lopez C, Metges J, Ruiz A, Calvo M, Strickland A, Kannourakis G, Muro K, Kawakami H, Wei J, Borg C, Zhu Z, Gupta N, Pelham R, Shen L
Publicada:
1 jun 2023
Ahead of Print:
1 jun 2023
Resumen:
BackgroundPoly (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.MethodsThe 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.ResultsIn 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.ConclusionsMaintenance 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.
Filiaciones:
Ciardiello F:
Univ Campania Luigi Vanvitelli, Dipartimento Med Precis, Caserta, Italy
Bang Y:
Seoul Natl Univ, Dept Internal Med, Coll Med, Seoul, South Korea
Cervantes A:
Univ Valencia, Biomed Res Inst INCLIVA, Dept Med Oncol, CIBERONC, Valencia, Spain
Dvorkin M:
St Petersburg Acad Univ, Russian Acad Sci, Algorithm Biol Lab, St Petersburg, Russia
Lopez C:
Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Med, Portland, OR USA
Metges J:
CHU Morvan, Arpego Network, Inst Oncol & Haematol, Brest, France
Ruiz A:
Hosp Puerta Hierro Majadohonda, Madrid, Spain
Calvo M:
Inst Catala Oncol Hosp, Dept Med Oncol, ONCOBELL Program IDIBELL, Barcelona, Spain
Strickland A:
Monash Univ, Dept Med Oncol, Monash Hlth, Melbourne, Vic, Australia
Kannourakis G:
Ballarat Oncol & Haematol Serv, Wendouree, Vic, Australia
Fiona Elsey Canc Res Inst, Ballarat, Vic, Australia
Muro K:
Aichi Canc Ctr Hosp, Dept Clin Oncol, Nagoya, Japan
Kawakami H:
Kindai Univ, Dept Med Oncol, Fac Med, Osaka, Japan
Wei J:
Nanjing Univ, Comprehens Canc Ctr Drum Tower Hosp, Med Sch, Nanjing, Peoples R China
Nanjing Univ, Clin Canc Inst, Nanjing, Peoples R China
Borg C:
Univ Hosp Besancon, Med Oncol Dept, CIC BT1431, Besancon, France
INSERM, Mol & Cellular Immune Therapies Canc, UMR1098, Besancon, France
Zhu Z:
BeiGene Ltd, Clin Dev, Cambridge, MA USA
Gupta N:
BeiGene Ltd, Clin Dev, Cambridge, MA USA
Pelham R:
BeiGene Ltd, Clin Dev, Cambridge, MA USA
Shen L:
Peking Univ Canc Hosp & Inst, Minist Educ Beijing, Dept Gastrointestinal Oncol, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China
Peking Univ Canc Hosp & Inst, Dept Gastrointestinal Oncol, 52 Fucheng Rd, Beijing 100142, Peoples R China
gold, Green Published
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