LBA37 - Atezolizumab (atezo) combined with platinum-based chemotherapy (CT) and maintenance niraparib for recurrent ovarian cancer (rOC) with a platinum-free interval (TFIp) >6 months: Primary analysis of the double-blind placebo (pbo)-controlled ENGOT-Ov41/GEICO 69-O/ANITA phase III trial

Background

Standard therapy for late-relapsing (TFIp >6 mo) rOC includes PARPi maintenance if disease responds to platinum-based CT. ANITA (NCT03598270) is the first-reported phase 3 trial evaluating atezo with platinum-based CT and maintenance PARPi in late-relapsing rOC.

Methods

Eligible pts had measurable high-grade serous, endometrioid or undifferentiated rOC, ≤2 prior CT lines (most recent including platinum) and TFIp >6 mo. Prior PARPi for rOC and/or prior immune checkpoint inhibitor were prohibited. Pts were stratified by carboplatin (carbo) doublet (paclitaxel, gemcitabine or pegylated liposomal doxorubicin [PLD]), TFIp (6–12 vs >12 mo), BRCA status (mutated vs non-mutated) and PD-L1 status (PD-L1-expressing immune cells on <1% vs ≥1% tumour area vs non-informative by SP142). Pts were randomised 1:1 to a carbo doublet + atezo or pbo for 6 cycles followed (in pts without progression on CT) by maintenance niraparib at an individualised starting dose + atezo or pbo until disease progression. The atezo dose was 1200 mg q3w or 840 mg q2w depending on the CT regimen. The primary endpoint was investigator-assessed progression-free survival (PFS) per RECIST v1.1.

Results

Between Nov 2018 and Jan 2022, 417 pts were randomised (14% BRCAm, 36% PD-L1+, 66% TFIp >12 mo, 11% prior PARPi after front-line CT, 54% prior bevacizumab); most (71%) received carbo–PLD and 74% began maintenance. At the data cut-off (15 Apr 2023), median follow-up was 36 mo. PFS results (Table) were consistent in key subgroups. Overall response to CT was 43% (95% CI 36–49%) and 45% (95% CI 39–52%) in the pbo and atezo arms, respectively. The safety profile was as expected from prior experience of these drugs. Table: LBA37

^aUnadjusted estimate.

Conclusions

Combining atezo with CT and maintenance niraparib for late-relapsing rOC did not significantly improve PFS or ORR.

Clinical trial identification

NCT03598270, EudraCT 2018-000366-11.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd).

Legal entity responsible for the study

GEICO.

Funding

F. Hoffmann-La Roche Ltd and GSK.

Disclosure

A. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, Genmab, Alkermes, Sutro, Roche, Sotio, PharmaMar, Oncoinvent, Novartis, Mersana, MSD, Macrogenics, Eisai, Inmunogen, Regeneron, HederaDx, Illumina; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis, Roche, Novocure, MSD, Takeda, Zaylab; Financial Interests, Institutional, Coordinating PI, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Steering Committee Member, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Coordinating PI, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Coordinating PI, ENGOT PI of AVB-500 phase III trial: Aravive. F. Heitz: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, GSK, NovoCure; Financial Interests, Personal, Invited Speaker: AstraZenecA, GSK. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, AstraZeneca, MSD/Merck, Clovis Oncology, GSK, Immunogen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca; 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, Personal, Invited Speaker: MSD/Merck; Financial Interests, Personal, Invited Speaker, Speaker: GSK; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, GSK; Non-Financial Interests, Other, Steering Committee, member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO (Alleanza contro il tumore ovarico). T. Van Gorp: Financial Interests, Institutional, Advisory Board, Jan-2021 until 09-2022: AstraZeneca; Financial Interests, Institutional, Other, Travel costs: AstraZeneca, GSK, MSD/Merck, PharmaMar; Financial Interests, Institutional, Advisory Board, Jan-2021: Eisai; Financial Interests, Institutional, Advisory Board, May-2021 until present: GSK; Financial Interests, Institutional, Invited Speaker, Apr 2022: GSK; Financial Interests, Institutional, Advisory Board, Apr-2021 until present: MSD; Financial Interests, Institutional, Advisory Board, Feb-2021: OncXerna Therapeutics; Financial Interests, Institutional, Advisory Board, Feb 2023 until present: Tubulis; Financial Interests, Institutional, Advisory Board: ImmunoGen; Financial Interests, Institutional, Research Grant, Oct-2020 until Oct-2021: Amgen; Financial Interests, Institutional, Research Grant, Oct-2020 until Oct-2022: Roche; Financial Interests, Institutional, Research Grant, Jan 2022 until Mar 2023: AstraZeneca. A. Oaknin: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, EMD Serono, Eisai, F. Hoffmann-La Roche, GSK, Genmab, Immunogen, Itheos, Merck Sharps & Dohme de España, SA, Mersana Therapeutics, Novocure, OncXerna Therapeutics, Inc, PharmaMar, Regeneron, Sattucklabs, Seagen, Sutro Biopharma, Exelisis; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Amgen, AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Aprea Therapeutics AB, Regeneron Pharmaceuticals, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO; Non-Financial Interests, Leadership Role, ESMO GYN Co-Chair 2023 - 2025: ESMO; Non-Financial Interests, Leadership Role, Chair de Cervix Committee. 2022-2024: GCIG; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape; Financial Interests, Personal, Writing Engagement, Educational: Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AZ, Clovis, Ability Pharma, MSD, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AZ, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Other, consultancy: Owkin; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AZ; Financial Interests, Institutional, Funding, CI clinical trial: AZ; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AZ; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer; Non-Financial Interests, Member: GCIG. L. Gaba Garcia: Financial Interests, Personal, Advisory Board: GSK, PharmaMar, AstraZeneca, AstraZeneca, MSD, Clovis Oncology; Financial Interests, Personal, Invited Speaker: GSK, MSD, Clovis Oncology. C. Lebreton: Financial Interests, Personal, Advisory Board: GSK, GSK, MSD, EISAI, CLOVIS oncology. M. Romeo Marin: Financial Interests, Personal, Advisory Board, Educational purposes: MSD; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: AZ; Financial Interests, Institutional, Local PI: Tesaro, MSD, Roche, IMNG. A. Redondo: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, GSK, Clovis, PharmaMar; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK, Clovis, PharmaMar; Financial Interests, Institutional, Local PI: Roche, Eisai, 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. J.A. Perez Fidalgo: Financial Interests, Personal, Invited Speaker: AstraZeneca, Clovis, GSK, PharmaMar; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Clovis, PharmaMar, Roche, Abilify Pharma; Financial Interests, Personal, Full or part-time Employment, Associate Professor: University of Valencia; Financial Interests, Institutional, Research Grant: GSK, PharmaMar; Financial Interests, Institutional, Funding: Novartis, GSK; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Financial Interests, Personal, Steering Committee Member: AstraZeneca, Artios Pharma; Non-Financial Interests, Project Lead, Coordinating PI Phase III trial in breast cancer: Novartis; Non-Financial Interests, Member, Member of the Early Drug Development working group: ENGOT; Non-Financial Interests, Leadership Role, Member of the Executive Committee and Head of the Scientific Committee: GEICO; Non-Financial Interests, Leadership Role, Member of the Executive Commitee and co-coordinator of Uterine Sarcoma Group: GEIS; Non-Financial Interests, Leadership Role, Co-chair Phase 2 group: GCIG; Non-Financial Interests, Member: BIG; Non-Financial Interests, Member, Adolescent and Young Adults working group: SEOM. A. Santaballa Bertran: Financial Interests, Personal, Advisory Board: Clovis, GSK, MSD, Astra; Financial Interests, Personal, Invited Speaker: Clovis, GSK, Astra, MSD. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Esai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. F. Selle: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, GSK/Tesaro, Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, GSK/Tesaro. All other authors have declared no conflicts of interest.