LBA29 - Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC)

Background

In the PAOLA-1/ENGOT-ov25 (NCT02477644) primary analysis, adding ola to maintenance bev after first-line (1L) platinum-based chemotherapy (PBC) + bev led to a significant progression-free survival (PFS) benefit in AOC (HR 0.59, 95% CI 0.49–0.72; P<0.001), particularly in pts with homologous recombination deficiency (HRD+; BRCA1/2 mutation [BRCAm] and/or genomic instability; Ray-Coquard et al NEJM 2019). Here, we report the prespecified final OS analysis.

Methods

Pts with high-grade AOC, in response after PBC + bev, were randomized 2:1 to ola tablets (300 mg bid; up to 24 months [mo]) + bev (15 mg/kg q3w; 15 mo total) or placebo [pbo] + bev. OS (intent-to-treat [ITT] population) was a key secondary endpoint, with analysis planned for 3 years (y) after the primary analysis as part of hierarchical testing.

Results

537 pts were randomized to ola + bev and 269 to pbo + bev (median follow-up 61.7 and 61.9 mo, respectively; OS data maturity: 55.3%). Median OS in the ITT population was 56.5 mo with ola + bev vs 51.6 mo with pbo + bev (HR 0.92, 95% CI 0.76–1.12; P=0.4118; OS at 5 y, 47.3 vs 41.5%). In HRD+ pts, OS was prolonged with ola + bev (HR 0.62, 95% CI 0.45–0.85; OS at 5 y, 65.5 vs 48.4%), with benefit in HRD+ pts with or without a tumour BRCAm (tBRCAm; Table). No benefit was seen in HRD- pts (HR 1.19, 95% CI 0.88–1.63). Subsequent PARP inhibitor therapy was received by 105 (19.6%) ola + bev pts vs 123 (45.7%) pbo + bev pts. Myelodysplastic syndrome, acute myeloid leukaemia and aplastic anaemia incidence, and new primary malignancy incidence, was respectively: ola + bev, 9 pts [1.6%] and 22 pts [4.1%]; pbo + bev, 6 pts [2.2%]) and 8 pts [2.9%]). Table: 000LBA29

*tBRCAm status by central labs; HRD status by Myriad myChoice HRD Plus ^§Preplanned exploratory analysis

Conclusions

Despite a high proportion of pts in the control arm receiving a PARP inhibitor post-progression, ola + bev provided a clinically meaningful improvement in OS for 1L HRD+ pts with and without a tBRCAm, confirming ola + bev as standard of care in this setting.

Clinical trial identification

NCT02477644.

Editorial acknowledgement

Medical writing assistance was provided by Rachel Dodd, PhD, 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

I.L. Ray-Coquard: Financial Interests, Personal, Other, Honoraria: AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; Financial Interests, Institutional, Other, Honoraria: GSK, MSD, Roche and BMS; Financial Interests, Personal, Advisory Role: AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; Financial Interests, Personal, Research Grant: MSD, Roche and BMS; Financial Interests, Institutional, Research Grant: MSD, Roche, BMS, Novartis, AstraZeneca and Merck Sereno; Financial Interests, Personal, Other, Travel: Roche, AstraZeneca and GSK. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape, Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AZ, Clovis, Ability Pharma, MSD, Tesaro, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: Tesaro, AZ, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; 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, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer. S. Pignata: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Merck Sharp & Dohme, Pfizer, Tesaro, Clovis Oncology, and PharmaMar. A.J. Gonzalez Martin: Financial Interests, Personal, Advisory Role: Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, macrogenmics, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, Sotio, and Sutro; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, PharmaMar, Roche, GSK, and Clovis; Financial Interests, Personal, Research Grant: Roche, and TESARO; Financial Interests, Personal, Other, Travel expenses: AstraZeneca, PharmaMar Roche, and TESARO. G. Bogner: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche and GSK; Financial Interests, Personal, Sponsor/Funding, Medical conferences: AstraZeneca, Roche and GSK. I.B. Vergote: Financial Interests, Personal, Other, Consulting/advidory: Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Seagen, Sotio; Financial Interests, Institutional, Research Grant: Oncoinvent AS, Amgen, Roche; Financial Interests, Personal, Other, Travel/accommodation: Karyopharm. N. Colombo: Financial Interests, Personal, Other, Honoraria: Roche/Genentech, AstraZeneca, Tesaro and PharmaMar; Financial Interests, Personal, Advisory Role: Roche/Genentech, PharmaMar, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, Takeda, Tesaro, BioCad and GSK. J. Maenpaa: Financial Interests, Personal, Other, Honoraria: AstraZeneca and GSK. F. Selle: Financial Interests, Personal, Other, Honoraria: AstraZeneca, GSK Tesaro, MSD, Sandoz (Novartis), and Clovis Oncology; Financial Interests, Institutional, Funding: Roche, GSK Tesaro, AstraZeneca, Immunogen, MSD, Incyte, and Agenus. B. Schmalfeldt: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD; Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD; Financial Interests, Personal, Funding: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD; Financial Interests, Personal, Other, Travel/accommodation: Roche, AstraZeneca, Tesaro. G. Scambia: Financial Interests, Personal, Research Grant: MSD Italia S.r.l.; Financial Interests, Personal, Other, Consulting: Johnson & Johnson, and TESARO Bio Italy S.r.l; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology Italy Srl and MSD Italia Srl. E.M. Guerra Alia: Financial Interests, Personal, Advisory Role: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, PharmaMar, Roche, GSK; Financial Interests, Personal, Other, Travel/accommodation: Roche, Tesaro: A GSK Company and Baxter. C. Lefeuvre-Plesse: Financial Interests, Personal, Other, Honoraria: Pfizer, AstraZeneca, Roche, Daiichi-Sankyo; Financial Interests, Personal, Other, Travel/accommodation: Roche, Novartis, Pfizer, Pierre Fabre. A. Belau: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Clovis, MSD, Daiichi Sankyo Company, Lilly, Seagen; Financial Interests, Personal, Advisory Role: Pfizer, Roche, AstraZeneca, MSD, Lilly, Daiichi Sankyo Company, Seagen; Financial Interests, Personal, Other, Travel/accommodation: Roche, AstraZeneca, Daiichi Sankyo Company . A. lortholary: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD and Tesaro; Financial Interests, Personal, Invited Speaker, Honoraria: Clovis Oncology, and Roche; Financial Interests, Personal, Other, Participation in medical congress: Novartis, Pfizer, MSD, Lilly and Roche. E. Pujade-Lauraine: Financial Interests, Personal, Invited Speaker: AstraZeneca, Tesaro, and Roche, Clovis Oncology, Incyte, and Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Tesaro, and Roche; Financial Interests, Personal, Other, Travel: AstraZeneca, Tesaro, and Roche; Financial Interests, Personal, Full or part-time Employment: ARCAGY Research. P. Harter: Financial Interests, Personal, Other, Honoraria: straZeneca, Roche, Clovis Oncology, Stryker, MSD Oncology, Zai Lab, Lilly, Sotio, Esai, GlaxoSmithKline; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Tesaro, Merck, GlaxoSmithKline, Clovis Oncology, Immunogen; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Genmab, GlaxoSmithKline, Immunogen, and Colvis Oncology. All other authors have declared no conflicts of interest.