1191OPhase II study of olaparib (O) and durvalumab (D) (MEDIOLA): Updated results in patients (pts) with germline BRCA-mutated (gBRCAm) metastatic breast cancer (MBC)

Abstract Background O (olaparib, Lynparza®) is approved for gBRCAm HER2(-) MBC based on the OlympiAD study. O-induced DNA damage may increase tumor antigen release, activate cGAS/STING, attract tumor-infiltrating lymphocytes and upregulate programmed cell death ligand-1 (PD-L1). In OlympiAD (single-agent olaparib), median duration of response (DoR) and median progression-free survival (PFS) were 6.4 months (m) and 7.0 m, respectively. MEDIOLA assessed the efficacy and safety of the combination of O and D (durvalumab, Imfinzi®), an anti-PD-L1 antibody, in gBRCAm HER2(-) MBC (NCT02734004). Early results were reported (SABCS 2017 PD6-11, 2018 PD5-04). Methods Pts with gBRCAm HER2(-) MBC were eligible; prior platinum was allowed; prior PARPi or anti-PD(L)1 was not. Pts received O 300 mg BID for a 4-wk run-in, then O 300 mg BID and D 1.5g IV q 4 wks until disease progression. Tumors were assessed at baseline, 4 wks, then every 8 wks. Dual primary endpoints were disease control rate (DCR) at 12 wks and safety. Secondary endpoints were 28-wk DCR, objective response rate (ORR), DoR, PFS, overall survival (OS), and biomarker analysis. Results 34 pts were in the safety, and 30 pts in the efficacy analyses. The 12-wk DCR was 24/30 (80%), greater than the target of 75%. The 28-wk DCR was 15/30 (50%). Other efficacy endpoints are presented below. The most common adverse events ≥Grade 3: anemia (Gr 3, 4 pts), neutropenia (Gr 3, 3 pts), and pancreatitis (Gr 3, 1pt, Gr 4, 1 pt). Efficacy and safety results with longer follow-up will be presented. Efficacy results correlated to genomic data and intrinsic subtypes will also be presented. Table . 1191O Endpoint Overall Cohort (n = 30) 0 prior lines n = 9 (7/9 TNBC) 1 prior line n = 11 (5/11 TNBC) 2 prior lines n = 10 (5/10 TNBC) mPFS (mo) (95% CI) 8.2 (4.6, 11.8) 9.9 (2.2, 13.8) 11.7 (1.9, NC) 6.5 (1.0, 8.2) mOS (mo) (95% CI) 20.5 (16.2, 23.9) 21.3 (9.0, NC) 22.7 (10.1, NC) 16.9 (4.6, NC) Responses 19 7 7 5 ORR (95% CI) 63.3% (43.9-80.1) 78% (40.0, 97.2) 64% (30.8, 89.1) 50% (18.7, 81.3) mDoR (mo) (IQR) 9.2 (5.5, 20.3) 9.2 (4.0, 12.9) NC (10.9, NC) 5.5 (5.4, 5.5) IQR, interquartile range; NC, not calculable; TNBC, triple-negative breast cancer Conclusions The data suggest that pts with fewer prior lines of chemotherapy (0/1) had higher ORR, longer mDoR, mPFS and mOS than those with 2 prior lines. The chemo-free combination was well-tolerated, with safety consistent with the individual agent profiles. Confirmation of these results in early-line patients is warranted. Clinical trial identification NCT02734004. Editorial acknowledgement Writing assistance was provided by Martin Goulding, PhD, of Mudskipper Ltd and funded by AstraZeneca. Legal entity responsible for the study AstraZeneca and the authors. Funding AstraZeneca. Disclosure S. Domchek: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Clovis Oncology; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (self): PharmaMar. S. Postel-Vinay: Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: AstraZeneca; Research grant / Funding (self), Non-remunerated activity/ies: Boehringer Ingelheim; Research grant / Funding (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Research grant / Funding (institution): Janssen-Cilag; Advisory / Consultancy, Research grant / Funding (self), Non-remunerated activity/ies: Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self), Non-remunerated activity/ies: Pfizer; Research grant / Funding (self), Non-remunerated activity/ies: Roche; Research grant / Funding (self): Sanofi; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: Johnson & Johnson; Non-remunerated activity/ies: Lilly; Non-remunerated activity/ies: MedImmune; Non-remunerated activity/ies: NH TherAGuiX. S. Im: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche. J. Alexandre: Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): PharmaMar; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self): Ipsen; Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen. M.G. Krebs: Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy: Octimet; Advisory / Consultancy: Achilles; Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (self), Travel / Accommodation / Expenses: BerGenBio; Research grant / Funding (self): MSD. M. Lanasa: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H.K. Angell: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Z. Lai: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. C. Gresty: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. L.M. Opincar: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Herbolsheimer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. B. Kaufman: Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.