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<p>Single-agent maintenance poly(ADP-ribose) polymerase (PARP) inhibition may represent an effective strategy in patients with advanced/metastatic endometrial cancer responding to platinum-based chemotherapy, including for molecular subtypes with suboptimal options. To explore this approach, we initiated the randomized phase IIb UTOLA trial (NCT03745950). Female patients without progression following front-line platinum-based chemotherapy for advanced/metastatic endometrial cancer were randomized 2:1 to twice-daily maintenance oral olaparib 300 mg or placebo until progression or intolerance, stratified by p53 status, mismatch repair status, and response to initial chemotherapy. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Secondary endpoints were PFS in subgroups, time to second progression or death, time to first and second subsequent therapy, objective response rate, overall survival, patient-reported outcomes, and safety. In the intention-to-treat population (<i>n</i> = 145), there was no PFS difference between olaparib and placebo (median 5.6 vs. 4.0 months, respectively; hazard ratio 0.94, 95% confidence interval 0.65–1.35; <i>p</i> = 0.74). However, intriguing numerical PFS effects were observed in exploratory analyses of pre-specified subgroups (p53-abnormal, complete response to initial chemotherapy, chromosomal instability). There was no overall survival difference between treatments. Grade 3/4 adverse events occurred in 36% versus 10% of olaparib- versus placebo-treated patients and were consistent with the olaparib safety profile in other cancers. Maintenance olaparib did not improve PFS, but promising numerical effects in subsets of patients warrant prospective evaluation.</p>

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Maintenance olaparib after platinum-based chemotherapy for advanced/metastatic endometrial cancer: GINECO randomized phase IIb UTOLA trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月26日

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  • Florence Joly,
  • Alexandra Leary,
  • Isabelle Ray-Coquard,
  • Bernard Asselain,
  • Manuel Rodrigues,
  • Laurence Gladieff,
  • Guillaume Meynard,
  • Sophie Abadie-Lacourtoisie,
  • Coriolan Lebreton,
  • Leïla Bengrine Lefevre,
  • Pierre Fournel,
  • Rémy Largillier,
  • Frédéric Selle,
  • Jean-Sébastian Frenel,
  • Yolanda Fernandez Diez,
  • Cyril Foa,
  • Philippe Follana,
  • Jérôme Meunier,
  • Michel Fabbro,
  • Anne-Claire Hardy Bessard,
  • Isabelle Cojean-Zelek,
  • Emilie Kaczmarek,
  • Elise Bonnet,
  • Antoine Arnaud,
  • Sophie Roche,
  • Karen Leroy,
  • Pierre-Alexandre Just,
  • Raphaël Leman,
  • Corinne Jeanne,
  • Céline Callens,
  • Benoit You,
  • Jérôme Alexandre

摘要

Single-agent maintenance poly(ADP-ribose) polymerase (PARP) inhibition may represent an effective strategy in patients with advanced/metastatic endometrial cancer responding to platinum-based chemotherapy, including for molecular subtypes with suboptimal options. To explore this approach, we initiated the randomized phase IIb UTOLA trial (NCT03745950). Female patients without progression following front-line platinum-based chemotherapy for advanced/metastatic endometrial cancer were randomized 2:1 to twice-daily maintenance oral olaparib 300 mg or placebo until progression or intolerance, stratified by p53 status, mismatch repair status, and response to initial chemotherapy. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Secondary endpoints were PFS in subgroups, time to second progression or death, time to first and second subsequent therapy, objective response rate, overall survival, patient-reported outcomes, and safety. In the intention-to-treat population (n = 145), there was no PFS difference between olaparib and placebo (median 5.6 vs. 4.0 months, respectively; hazard ratio 0.94, 95% confidence interval 0.65–1.35; p = 0.74). However, intriguing numerical PFS effects were observed in exploratory analyses of pre-specified subgroups (p53-abnormal, complete response to initial chemotherapy, chromosomal instability). There was no overall survival difference between treatments. Grade 3/4 adverse events occurred in 36% versus 10% of olaparib- versus placebo-treated patients and were consistent with the olaparib safety profile in other cancers. Maintenance olaparib did not improve PFS, but promising numerical effects in subsets of patients warrant prospective evaluation.