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

© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Cancer medicine - 12(2023), 12 vom: 13. Juni, Seite 13145-13154

Sprache:

Englisch

Beteiligte Personen:

Ciardiello, Fortunato [VerfasserIn]
Bang, Yung-Jue [VerfasserIn]
Cervantes, Andrés [VerfasserIn]
Dvorkin, Mikhail [VerfasserIn]
Lopez, Charles D [VerfasserIn]
Metges, Jean-Philippe [VerfasserIn]
Sánchez Ruiz, Antonio [VerfasserIn]
Calvo, Mariona [VerfasserIn]
Strickland, Andrew H [VerfasserIn]
Kannourakis, George [VerfasserIn]
Muro, Kei [VerfasserIn]
Kawakami, Hisato [VerfasserIn]
Wei, Jia [VerfasserIn]
Borg, Christophe [VerfasserIn]
Zhu, Zhaoyin [VerfasserIn]
Gupta, Neal [VerfasserIn]
Pelham, Robert J [VerfasserIn]
Shen, Lin [VerfasserIn]

Links:

Volltext

Themen:

49DFR088MY
8375F9S90C
Clinical Trial, Phase II
Clinical trial
Fluorenes
Gastric cancer
Journal Article
Maintenance
Pamiparib
Phase 2
Platinum
Poly(ADP-ribose) polymerase inhibitors
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 04.07.2023

Date Revised 05.07.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/cam4.5997

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM35762260X