36MO - Maintenance olaparib plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (OC): 5-year (y) progression-free survival (PFS) by molecular subgroup in the PAOLA-1/ENGOT-ov25 trial

Background

The first-line setting represents the only opportunity for cure in advanced OC. 5-y PFS rates may predict cure as most pts not relapsing at 5 years are potentially cured. In the final overall survival (OS) analysis of the Phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644), maintenance olaparib + bev provided a clinically meaningful OS benefit vs placebo (pbo) + bev in pts with newly diagnosed advanced OC who tested positive for homologous recombination deficiency (HRD+; tumour BRCA1/2 mutation [tBRCAm] and/or genomic instability) regardless of tBRCAm status (Ray-Coquard et al. Ann Oncol 2022:LBA29). We evaluated 5-y PFS by molecular subgroup to help inform the potential for cure.

Methods

Pts in response after platinum-based chemotherapy + bev were randomized 2:1 to olaparib (300 mg bid for up to 24 months) + bev (15 mg/kg q3w for up to 15 months) or pbo + bev. A post hoc, updated descriptive PFS analysis by molecular subgroup was conducted at the final OS data cutoff (DCO).

Results

537 pts were randomized to olaparib + bev and 269 to pbo + bev (median PFS follow-up in censored pts was 56.7 and 57.8 months, respectively). At DCO (22 March 2022), the 5-y PFS rate was 46% with olaparib + bev vs 19% with pbo + bev in the HRD+ group, 50% vs 25%, respectively, in the tBRCAm group, 41% vs 15%, respectively, in the HRD+ excluding tBRCAm group, 13% vs 13%, respectively, in the HRD−/unknown group, and 8% vs 12%, respectively, in the HRD− group. Updated data for time to first or second subsequent therapy or death will be presented.Table: 36MO
Figure 1

Conclusions

The 5-y updated descriptive PFS rates suggest the benefit of adding olaparib to bev is sustained beyond end of treatment and may indicate the potential of cure in HRD+ newly diagnosed advanced OC, supporting use of maintenance olaparib + bev as a standard of care in pts with HRD+ tumours, regardless of tBRCAm status.

Clinical trial identification

NCT02477644.

Editorial acknowledgement

Medical writing assistance was provided by Abbie Newman BSc, at Cence, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

ARCAGY Research.

Funding

ARCAGY Research, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and F. Hoffmann-La Roche.

Disclosure

A.J. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, Genmab, Alkermes, Sutro, Roche, SOTIO, PharmaMar, Oncoinvent, Novartis, Mersana, MSD, Macrogenics, Eisai, ImmunoGen, Regeneron, HederaDx, Illumina; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis, Roche, Novocure, MSD, Takeda, Zaylab; Financial Interests, Institutional, Invited Speaker, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Invited Speaker, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Invited Speaker, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Invited Speaker, ENGOT PI of AVB-500 phase III trial: ARAVIVE. J. Medioni: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Gilead, Lilly-Eli; Non-Financial Interests, Personal, Other, Travelling facilities: Pfizer. P. Harter: Financial Interests, Personal, Advisory Board, Value includes honoraria for lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, includes honoraria for lectures: GSK, Roche, MSD; Financial Interests, Personal, Invited Speaker: Amgen, Stryker, Zailab, Eisai; Financial Interests, Personal, Advisory Board: Clovis, Immunogen, Novartis, Mersana; Financial Interests, Personal, Other, IDMC member: Sotio; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, GSK, Genmab, Immunogen; Financial Interests, Institutional, Funding: Seagen, Clovis; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca. S. Cinieri: Financial Interests, Institutional, Other: Lilly Oncology. I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Oncoinvent AS (2019-2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020). S. Hietanen: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD. M.J. Rodrigues: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, GSK, Immunocore; Financial Interests, Personal, Research Grant: MSD, BMS. L.C. Hanker: Financial Interests, Personal, Advisory Board: Amgen, Roche, GSK, MSD, AstraZeneca. C. Zamagni: Financial Interests, Personal and Institutional, Research Grant: Roche, Novartis, AstraZeneca, Pfizer, Tesaro, Pierre Fabre, 1st. Gentili, Teva, Seagen; Financial Interests, Personal, Research Grant: Eisai, PharmaMar, Eli Lilly, Celgene, MSD, GSK, Amgen, Daiichi Sankyoi; Financial Interests, Personal, Advisory Board: Roche, Eisai, Novartis, AstraZeneca, Pfizer, PharmaMar, Tesaro, QuintikesIMS, Eli Lilly, Celegene, MSD, GSK, Daiichi Sankyo; Financial Interests, Personal, Other, Other financial or non-financial interests: Roche, Novartis, AstraZeneca, Pfizer, Amgen, Tesaro, QuintikesIMS, MSD, GSK, Daiichi Sankyo. S. Hernando Polo: Financial Interests, Institutional, Full or part-time Employment: Hospital Universitario Fundacion Alcorcón; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, GSK, Pfizer, Clovis. D. Bauerschlag: Financial Interests, Personal, Advisory Board: AstraZeneca. B. You: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK-TESARO, Bayer, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad. P. Hillemanns: Financial Interests, Personal, Invited Speaker, Lecture Fee: Roche, MSD, AstraZeneca. E. Pujade-Lauraine: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca; Financial Interests, Personal, Member, IDMC board: Agenus, Incyte; Financial Interests, Personal, Full or part-time Employment: ARCAGY. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, 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, Personal, Principal Investigator: PAOLA1; Non-Financial Interests, Personal, Other, President: GINECO. All other authors have declared no conflicts of interest.