529MO - Phase II study of olaparib plus durvalumab with or without bevacizumab (MEDIOLA): Final analysis of overall survival in patients with non-germline BRCA-mutated platinum-sensitive relapsed ovarian cancer

Background

The MEDIOLA (NCT02734004) study evaluated the efficacy and safety of olaparib+durvalumab (O+D doublet cohort) and O+D+bevacizumab (O+D+B triplet cohort) in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC). Previous efficacy data showed median progression-free survival (PFS) (95% CI) of 5.5 (3.6–7.5) and 14.7 (10.0–18.1) months (mo) with O+D and O+D+B, respectively (Drew et al, ESMO 2020). We now present the final analysis of overall survival (OS) and disease control rate (DCR) at 56 weeks (wks) in the O+D and O+D+B cohorts.

Methods

Pts had confirmed non-gBRCAm PSR OC and received 1–2 prior lines of platinum-based chemotherapy. Pts received O (300 mg bid) and D (1.5 g IV q4w), and B (10 mg/kg IV q2w; O+D+B cohort only) until disease progression. Survival follow-up took place at treatment discontinuation, monthly for 4 mo, and every 2–3 mo thereafter. OS and DCR at 56 wks were secondary endpoints.

Results

32 pts received O+D and 31 pts received O+D+B; 24/32 (75%) O+D and 20/31 (65%) O+D+B pts had received one prior line of chemotherapy. At data cutoff (17 Sep 2021), median follow-up for OS was 23.2 mo for O+D and 31.9 mo for O+D+B. Kaplan–Meier estimates of median OS (95% CI) were 26.1 (18.7–not calculable [NC]) mo for O+D and 31.9 (22.1–NC) mo for O+D+B. Probabilities of survival (95% CI) in the O+D and O+D+B cohorts, respectively, were 77.6 (58.6–88.6) and 96.8 (79.2–99.5) at 12 mo and 50.8 (32.1–66.8) and 64.5 (45.2–78.5) at 24 mo. DCR at 56 wks (90% CI) was 9.4% (2.6–22.5) for O+D and 38.7% (24.1–55.0) for O+D+B. Safety data are shown in the Table. Table: 529MO

*Discontinuation of O, D, or B

Conclusions

Based on the reported final OS and DCR at 56 wks data, treatment with O+D+B demonstrated promising efficacy in pts with non-gBRCAm PSR OC. O+D and O+D+B safety profiles were consistent with that expected for the single agents; no new safety signals emerged with longer follow-up.

Clinical trial identification

NCT02734004.

Editorial acknowledgement

Medical writing assistance was provided by Caroline Wadsworth, PhD, at Cence, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca and GlaxoSmithKline; Financial Interests, Personal, Other, Consulting: Amgen, AstraZeneca, Genmabs, GlaxoSmithKline, Immunogen, Merck Sharpe & Dohme, Merck Sereno, and Shattuck Labs; Financial Interests, Personal, Other, Personal fees: Amgen, AstraZeneca, Clovis Oncology , Merck Sharpe & Dohme, Mersana, Pfizer, and Roche; Non-Financial Interests, Personal, Other, Unpaid participation: Epsilogen; Non-Financial Interests, Personal, Other, Unpaid role as Director of Membership: European Society of Medical Oncology. M. Imbimbo: Financial Interests, Personal, Advisory Role: Immatics. P. Roxburgh: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: AstraZeneca and Tesaro. J. Kim: Financial Interests, Personal, Advisory Role: Takeda Korea, GSK Korea, Boryung, Vifor Pharma, MSD Korea; CMIC Korea, AstraZeneca, Janssen, LG Pharma . M.H. Kim: Financial Interests, Personal, Research Grant: AstraZeneca. R. Plummer: Financial Interests, Personal, Other, Personal fees: Pierre Faber, Bayer, Novartis, BMS, Cybrexa, Ellipses, CV6 Therapeutics, Immunocore, Genmab, Astex Therapeutics, Medivir, Onxeo, Alligator Biosciences, GSK, SOTIO Biotech AG and Sanofi Aventis. S. Stemmer: Financial Interests, Institutional, Research Grant: CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelexis, Geicam, MSD, AbbVie, Tayga biopharmaceutics, Halozyme, Incyte, Lilly, Moderna, Teva pharmaceuticals, Roche; Financial Interests, Personal, Stock/Shares: CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, Remiwise, CAN-FITE. B. You: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Clovis, ECS Progastrin, GlaxoSmithKline, Merck Sharp & Dohme, Novartis and Roche; Financial Interests, Personal, Other, Travel support: AstraZeneca, Bayer Merck Sharp & Dohme and Roche. R.T. Penson: Financial Interests, Personal, Funding: Array BioPharma Inc., AstraZeneca, Eisai Inc., Genentech, Inc., Regeneron, Sanofi-Aventis US LLC, Tesaro Inc., Vascular Biogenics Ltd; Financial Interests, Personal, Royalties: BMJ Publishing, Elsevier, UptoDate, Wolters Kluwer Health, Wiley Blackwell; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Cancer Panels, Care4ward (unpaid), Eisai, Genentech, GlaxoSmithKline, Merck & Co., Roche Pharma, Sutro Biopharma, Vascular Biogenics, WebMD. D. O'Malley: Financial Interests, Personal, Funding: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, Bristol-Myers Sq; Financial Interests, Personal, Advisory Role: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche Ambry, GOGFoundation, Iovance, Myriad Genetics, Eisai, Agenus, Tarveda, Merck, SeaGen, Novartis, Mersana, Clovis, Rubis, Elevar, Takeda, Toray, INXMED, S. K. Meyer: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H. Gao: Financial Interests, Personal, Full or part-time Employment, employment or stock ownership with AstraZeneca: AstraZeneca; Financial Interests, Personal, Stocks/Shares, employment or stock ownership with AstraZeneca: AstraZeneca. H. Angell: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Tablante Nunes: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Domchek: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb and Clovis. Y. Drew: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, Genmab, Merck and Tesaro; Financial Interests, Institutional, Funding: AstraZeneca, Clovis Oncology, Genmab, Merck and Tesaro; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Clovis Oncology, Genmab, Merck and Tesaro. All other authors have declared no conflicts of interest.