LBA40 - Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent endometrial carcinoma

Background

The standard therapy for advanced/recurrent endometrial cancer includes carboplatin and paclitaxel (CP). Robust biological rationale suggested a synergy between immunotherapy and chemotherapy in this setting.

Methods

AtTEnd is an international academic study in endometrial carcinoma/carcinosarcoma patients (pts) with advanced newly diagnosed or recurrent disease with no prior systemic chemotherapy for recurrence. Pts were randomized (2:1 ratio) to receive either CP chemotherapy and atezolizumab (atezo) or placebo, followed by atezo or placebo until disease progression. The mismatch repair (MMR) status was evaluated centrally. Coprimary endpoints with a hierarchical approach were: progression free survival (PFS) in the deficient MMR (dMMR) population, PFS and overall survival (OS) in all comers.

Results

Five hundred and fifty-one pts were enrolled from Oct 2018 to Jan 2022 in 89 sites across 10 countries (median follow-up 28.3 months). Of the 549 pts included in the intention to treat population, 125 (22.8%) had dMMR tumours and 352 (64.1%) had endometrioid carcinoma; 369 (67.2%) had recurrent disease and 148 (82.2%) of newly diagnosed cases had primary stage IV. In the dMMR population, the addition of atezo showed a significant improved PFS (HR 0.36 95% CI:0.23-0.57; p=0.0005; median PFS: not reached vs. 6.9 months for atezo vs placebo). The superiority in PFS was confirmed in all comers (HR 0.74 95%CI:0.61-0.91; p=0.0219; median PFS: 10.1 months vs 8.9 months for atezo vs placebo). Interim analysis of OS in all comers indicated a trend in favor for atezo, despite 45 (24.3%) placebo patients received immunotherapy as subsequent therapy. Second PFS and duration of response in the dMMR population confirmed the efficacy of atezo. Grade≥3 adverse events occurred in 66.9% and 63.8% of pts in atezo vs placebo arm. Safety profile for CP + atezo was manageable and consistent with expected toxicities.

Conclusions

The addition of atezo to standard CP chemotherapy demonstrated a statistically significant improvement in PFS for pts with advanced/recurrent endometrial carcinomas with a substantial benefit in pts with dMMR carcinomas.

Clinical trial identification

EudraCT 2018-001072-37; NCT03603184.

Editorial acknowledgement

Legal entity responsible for the study

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, GSK, Pfizer, Immunogen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). K. Harano: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Takeda; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Chugai, Takeda; Financial Interests, Institutional, Research Grant: Merck, Daiichi Sankyo; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, Takeda; Non-Financial Interests, Principal Investigator: Merck, Chugai. Y. Antill: Financial Interests, Personal, Advisory Board: GSK, Eisai, MSD; Financial Interests, Personal, Advisory Board, Coordinating PI: AstraZeneca. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, EISAI, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Local PI: Roche, Novartis, Eisai, MSD, Vaccibody, GSK; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, Gilead/Immunomedics, German Breast Group, AGO Research GmbH; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. E. Petru: Financial Interests, Personal, Advisory Board, Attendance fees: AstraZeneca, EISAI, Lilly, GSK; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, EISAI, Lilly, GSK; Financial Interests, Personal, Advisory Board, Fees: MSD, Novartis, Pharma Mar, Roche, Seagen, Pierre fabre, Daiichi Sankyo, GILEAD; Financial Interests, Personal, Invited Speaker, Fees: MSD, Novartis, Roche, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Local PI, Fees to institution: AstraZeneca; Financial Interests, Institutional, Local PI, Patient Fees: Roche; Financial Interests, Institutional, Local PI, Fees: Daiichi Sankyo, Lilly, GSK, Novartis; Financial Interests, Institutional, Local PI, FEES: Seagen, Pierre Fabre. C. Lai: Non-Financial Interests, Personal, Coordinating PI, President: TGOG; Financial Interests, Personal, Full or part-time Employment: CGMH; Non-Financial Interests, Personal, Affiliate, Past President: TGOG. L. Fariñas Madrid: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Institutional, Invited Speaker: AstraZeneca&MSD; Financial Interests, Personal, Invited Speaker: EISAI, GSK. Y.C. Lee: Financial Interests, Institutional, Invited Speaker, Educational events: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Institutional, Research Grant: BeiGene. C. Zamagni: Financial Interests, Personal, Advisory Board: Roche, EISAI, Novartis, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Exact Sciences, MSD, GSK, Gilead, Seagen; Financial Interests, Institutional, Local PI: Roche, Novartis, AstraZeneca, Pfizer, Seagen, Medivation, AbbVie, Array BioPharma, Morphotek, Synthon, Daiichi-Sankyo, MSD, GSK, Gilead; Financial Interests, Personal, Other, Member of an Independent Data Monitoring Committee for an international clinical trial: AstraZeneca; Non-Financial Interests, Other, member of the Scientific Committee: LOTO Onlus, Susan J Komen Emilia-Romagna, Mamazone Sudtirol; Other, travel accomodation and partecipation expenses for scientific congresses: Roche, Novartis, Pfizer, Daiichi Sankyo, MSD, GSK, Gilead, AstraZeneca. G. Tasca: Financial Interests, Advisory Board: GSK, AstraZeneca, MSD; Financial Interests, Steering Committee Member: GSK; Financial Interests, Speaker’s Bureau: GSK, AstraZeneca; Financial Interests, Other, Travel Expenses: PharmaMar. M.P. Barretina Ginesta: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD, EISAI, PharmaMar; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, MSD; Financial Interests, Personal, Steering Committee Member: MSD. All other authors have declared no conflicts of interest.