761P - A phase II trial of avelumab in combination with pegylated liposomal doxorubicin in recurrent/metastatic endometrial cancer (GEICO 70-E): analysis according to molecular classification

Background

The Cancer Genome Atlas (TCGA) classified endometrial cancer (EC) into molecular subgroups with different prognosis and predictive value of response to immunotherapy or chemotherapy. Testing for surrogate biomarkers (BM) of TCGA groups may be clinically cost-effective. According to these BM groups, we evaluated differences in efficacy of avelumab (A) and pegylated liposomal doxorubicin (PLD) in recurrent EC pts.

Methods

Open-label, single-arm, multicenter, phase II study in recurrent/metastatic EC. Pts were treated with intravenous A 10 mg/kg (q2W) and PLD 40 mg/m² (q4W). Primary endpoint was 6 months (m) progression free survival (PFS). Archival tumor tissue was collected for molecular classification according to BM of the TGCA groups. POLE mutations, mismatch repair markers (MMR) and p53 abnormalities were analysed to classify EC tumors. EC groups were as follows: POLE (POLE mutant); P53-ABN (POLE wt, p53 abnormal): MSI (microsatellite instability) (POLE wt, p53 wt, abnormal MMR); MSS (microsatellite stable) (POLE wt, p53 wt, normal MMR). Differences in PFS and overall survival (OS) were evaluated among BM groups.

Results

BM analysis was performed in 41 pts: 26 (63.4%) were p53-ABN, 7 (17.1%) MSI, 7 (17.1%) non-specific molecular profile (NSMP), and 1 (2.4%) POLE. MSI/MSS classification showed 33 (80.5%) MSS tumors, 7 (17.1%) MSI, and 1 (2.4%) POLE. 6-m PFS was 45% [95% CI 31.9%-63.4%] with a median PFS of 5.68m [95% CI 3.58-7.98]. NSMP group showed the best PFS results: 6-m PFS, 66.7% and median, 9.2m (95% CI 1.7 – NR). 6-m PFS of MSI and P53-ABN groups was 28.6% and 42.3%, respectively. 6-m PFS was numerically better in MSS (46.9%) than in MSI (28.6%). Median OS time was 11.6m [95%CI; 7.4-NR] and 12-m OS was 47.5% [34.3%-65.8%]. Median OS in the NSMP, p53-ABN and MSI groups was 26.0m, 12.6m and 5.3m, respectively. OS was better in p53-ABN group than in MSI (HR: 3.44 [1.36; 8.69], p=0.01). OS was also better in MSS group than in MSI (HR: 3.78 [1.52; 9.43], p<0.01).

Conclusions

A and PLD has activity in pre-treated recurrent EC. Pts with MSS and p53-ABN had better outcomes than those with MSI. Interestingly pre-treated NSMP pts show a median OS >2 y.

Clinical trial identification

EudraCT number: 2018-000843-14.

Editorial acknowledgement

Legal entity responsible for the study

Grupo Español de Investigación en Cáncer de Ovario (GEICO).

Funding

Pfizer.

Disclosure

J.M. Piulats Rodriguez: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Roche, BMS, MSD, BeiGene, VCN, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: BMS, Pfizer, Janssen, BeiGene, Mirati. I. Palacio Vazquez: Financial Interests, Personal, Advisory Role: AstraZeneca/MSD, GSK, Eisai; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca/MSD, GSK, Novartis, Bristol; Financial Interests, Personal, Other, Travel/Accomodations, expenses: MSD, GSK, PharmaMar. J.D. Alarcon: Financial Interests, Personal, Financially compensated role: GSK, Clovis, Roche, AstraZeneca/MSD; Financial Interests, Personal, Advisory Role: GSK, Clovis, AstraZeneca/MSD; Financial Interests, Personal, Speaker’s Bureau: GSK, Clovis, Roche; Financial Interests, Personal, Expert Testimony: Clovis, GSK, AstraZeneca/MSD; Financial Interests, Personal, Other, Travel/Accomodations, expenses: GSK. M. Gil Martín: Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, PharmaMar; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other, Travel/Accomodations, expenses: PharmaMar/MSD, Clovis, GSK. L.M. Manso Sanchez: Financial Interests, Institutional, Funding: Clovis Oncology; Financial Interests, Personal, Research Grant: Tesaro/GSK; Financial Interests, Personal, Speaker, Consultant, Advisor: Tesaro/GSK, Pfizer, Novartis, AstraZeneca, Clovis Oncology, Eisai, Lilly, Pierre Fabre, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Novartis, Roche, Pfizer, Lilly. S. Hernando Polo: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK, Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, GSK, Pfizer; Financial Interests, Personal, Other, Travel/Accomodations, expenses: GSK. N. Ruiz: Financial Interests, Personal, Speaker’s Bureau: GSK, AstraZeneca, Clovis. X. Matias-Guiu: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Lilly, GSK, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Clovis; Non-Financial Interests, Other, Consultancy: AstraZeneca. M. Romeo Marin: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca; Financial Interests, Personal, Other, Travel/Accomodations, expenses: GSK, AstraZeneca/MSD. All other authors have declared no conflicts of interest.