Phase II study of olaparib + durvalumab (MEDIOLA): Updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC)

Abstract

Background

Olaparib (Lynparza®) is a poly(ADP-ribose) polymerase (PARP) inhibitor approved as maintenance treatment of PSR OC. MEDIOLA assessed olaparib in combination with the anti-programmed cell death ligand1 antibody, durvalumab, in germline BRCA1 and/or BRCA2 mutated (gBRCAm) PSR OC (NCT02734004). The 12-week (wk) disease control rate (DCR) = complete response [CR] + partial response + stable disease) was presented at SGO 2018 (late-breaker abst. 4).

Methods

Pts had PSR OC, gBRCA1 or gBRCA2 mutation, and had received at least one prior line of platinum. Pts received olaparib 300 mg PO BID for a 4-wk runin, then olaparib 300 mg PO BID and durvalumab 1.5 g IV q 4 wks until progressive disease. Tumours were assessed by RECIST 1.1 at baseline, 4 wks, then every 8 wks. Primary endpoints were 12wk DCR and safety. Secondary endpoints were 28-wk DCR, objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and biomarker analyses.

Results

Thirty-two/thirty-four pts treated were eligible. With the data cut-off on 1 Nov 2018, 28% pts were still on treatment. Most common ≥Grade 3 AEs were anaemia (17.6%), elevated lipase (11.8%), neutropenia (8.8%), and lymphopenia (8.8%). Five pts discontinued olaparib and three discontinued durvalumab due to an adverse event. The 28-wk DCR was 65.6% (90% CI: 49.6%, 79.4%). ORR was 71.9% (95% CI: 53.25%, 86.25%) with a total of seven CRs. Median PFS was 11.1 months (95% CI: 8.2, 15.9) with a median DoR of 10.2 months (25/75th percentile: 5.6, NC). Second-line pts (N = 13, 40.6%) had not yet reached the medians for PFS or DoR. Median OS for all pts was not yet reached, with 87.0% of pts alive at 24 months (median follow up = 20.4 months). Updated results will be presented.

Conclusions

The combination of olaparib and durvalumab was well tolerated and showed promising median PFS and DoR. Median PFS and DoR for pts with fewer prior lines of chemotherapy was not yet reached, suggesting that these pts may derive a greater benefit from the combination. The CR rate was higher than anticipated. This cohort has been expanded to further explore the durability of this chemotherapy-sparing combination.

Clinical trial identification

NCT02734004.

Editorial acknowledgement

Emma Robinson, Mudskipper Business, Ltd, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y. Drew: Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Tesaro ; Advisory / Consultancy: Genmab; Research grant / Funding (institution): Oncology; Research grant / Funding (institution): Veratsem. B. Kaufman: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Medison. S. Banerjee: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. P. Roxburgh: Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro. R.H. Alvarez: Honoraria (self): Eisai; Honoraria (self): Puma; Leadership role: Cancer Treatment Center of America. S. Domchek: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Clovis Oncology; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): PharmaMar. C. Gresty: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H.K. Angell: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. V. Rocher Ros: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. K. Meyer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Lanasa: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Herbolsheimer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.