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

Rákkutatás · Acute myeloid leukemia

Maintenance olaparib did not improve progression-free survival in the overall population, but numerical effects in subsets of patients warrant prospective evaluation.

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.

The study evaluates whether olaparib maintenance after platinum‑based chemotherapy benefits patients with advanced or metastatic endometrial cancer. Though the primary endpoint was not met, subgroup signals and safety data may guide future trials and inform clinical decision‑making for selected patients.

Bizonyítékszint: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.

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