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

Q: What was the main objective of the UTOLA trial?

To assess whether maintenance olaparib improves outcomes after disease control from first-line platinum-based chemotherapy in advanced/metastatic endometrial cancer.

Q: Did maintenance olaparib improve progression-free survival in the overall trial population?

No. In the intention-to-treat population, progression-free survival was not different between olaparib and placebo (median 5.6 vs 4.0 months; p=0.74).

Q: What safety differences were reported between olaparib and placebo?

Grade 3/4 adverse events occurred in 36% with olaparib versus 10% with placebo, consistent with olaparib’s safety profile in other cancers.

Sep 23, 2026

Uploaded by Grenda

Maintenance olaparib following platinum-based chemotherapy was evaluated as a potential strategy for patients with advanced/metastatic endometrial cancer who showed no progression. The randomized phase IIb UTOLA trial enrolled women randomized 2:1 to maintenance olaparib 300 mg twice daily or placebo until progression or intolerance, stratified by p53 status, mismatch repair status, and initial chemotherapy response. In the intention-to-treat population, olaparib did not improve progression-free survival (median 5.6 vs 4.0 months; HR 0.94; p=0.74) and no overall survival benefit was observed, while grade 3/4 adverse events were higher.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

UTOLA trial overview

Study design and endpoints

Results in intention-to-treat population

Subgroup analyses and safety

Background and rationale

Article [https://doi.org/10.1038/s41467-025-62678-x](https://doi.org/10.1038/s41467-025-62678-x) Maintenance olaparib after platinum-based chemotherapy for advanced/metastatic endometrial cancer: GINECO randomized phase IIb UTOLA trial Received: 7 March 2025 | Accepted: 28 July 2025 | | --- | | | | Check for updates | A list of authors and their afﬁliations appears at the end of the paper 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 p53status, 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 theolaparib safety proﬁle in other cancers. Maintenance olaparib did not improve PFS, but promising numerical effects in subsets of patients warrant prospective evaluation. Until recently, the prognosis for women with metastatic endometrial cancer (EC) was poor. Median overall survival (OS) was typically <2 years1, and there had been few advances in treatment options and the management of this disease. Platinum-based chemotherapy was administered universally as there were no known biomarkers to guide treatment or predict likely prognosis. More recently, diagnosis and treatment have become more personalized, reﬂecting disease heterogeneity2,3. ECisclassiﬁed according e-mail: [f.joly@baclesse.unicancer.fr](f.joly@baclesse.unicancer.fr) Fig. 1 | Patient ﬂow. aPatient required radiotherapy. bIncluding non-RECIST progression in 2 patients. RECIST, Response Evaluation Criteria in Solid Tumors. to molecular subtype, which provides prognostic information and is critical for treatment decision-making and patient selection. The molecular subtype associated with the worst prognosis is p53-abnormal, which is characterized by low tumor mutation burden but high somatic copy number alterations, suggestive of deﬁciencies in DNA repair pathways2–4. In contrast, mismatch repair (MMR)-deﬁcient (dMMR) and DNA polymerase epsilon(POLE) tumors are characterized by a high tumor mutational burden and low somatic copy number alterations. Tumors with no speciﬁc molecular proﬁle represent a heterogeneous group with frequent mutations in the PI3K/AKT/PTEN pathway and ARID1A tumor suppressor gene3. The enzyme poly(ADP-ribose) polymerase (PARP) is involved in base excision repair. Targeted therapies, such as olaparib, that inhibit PARP induce synthetic lethality in tumor cells that harbor homologous recombination deﬁciency (HRD)5. In ovarian cancer, PARP inhibitors are an established maintenance therapy in patients with HRD tumors responding to chemotherapy, particularly tumors harboring a BRCA mutation. PARP inhib

FAQs

What was the main objective of the UTOLA trial?

To assess whether maintenance olaparib improves outcomes after disease control from first-line platinum-based chemotherapy in advanced/metastatic endometrial cancer.

Did maintenance olaparib improve progression-free survival in the overall trial population?

No. In the intention-to-treat population, progression-free survival was not different between olaparib and placebo (median 5.6 vs 4.0 months; p=0.74).

What safety differences were reported between olaparib and placebo?

Grade 3/4 adverse events occurred in 36% with olaparib versus 10% with placebo, consistent with olaparib’s safety profile in other cancers.

Sep 23, 2026

Uploaded by Grenda