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Proffered Paper – Immunotherapy of cancer

4019 - Phase II study of olaparib (O) and durvalumab (D) (MEDIOLA): Updated results in patients (pts) with germline BRCA-mutated (gBRCAm) metastatic breast cancer (MBC)

Date

30 Sep 2019

Session

Proffered Paper – Immunotherapy of cancer

Topics

Immunotherapy

Tumour Site

Breast Cancer

Presenters

Susan Domchek

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

S. Domchek1, S. Postel-Vinay2, S. Im3, Y.H. Park4, J. Delord5, A. Italiano6, J. Alexandre7, B. You8, S. Bastian9, M.G. Krebs10, D. Wang11, S. Waqar12, M. Lanasa13, H.K. Angell14, Z. Lai15, C. Gresty14, L.M. Opincar16, P. Herbolsheimer16, B. Kaufman17

Author affiliations

  • 1 Basser Center, Unversity Of Pennsylvania, Private Practice - Domchek, 19104 - Philadelphia/US
  • 2 Drug Development Department, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 3 Department Of Internal Medicine, Seoul National University Hospital, 03080 - Seoul/KR
  • 4 Hematology-oncology, Samsung Medical Center, 135-710 - Seoul/KR
  • 5 Department Of Medical Oncology, Institut Universitaire du Cancer -Toulouse- Oncopole, 31059 - Toulouse/FR
  • 6 Early Phase Trials Unit, Institute Bergonié, 33076 - Bordeaux/FR
  • 7 -, Hôpital Cochin, - - Paris/FR
  • 8 Department Of Medical Oncology, Centre Hospitalier Lyon Sud, - - Pierre-Bénite/FR
  • 9 Department Of Medical Oncology, Kantonsspital Graubünden, 7000 - Chur/CH
  • 10 Experimental Cancer Medicine Team, The Christie NHS Foundation Trust and The University of Manchester, M204BX - Manchester/GB
  • 11 Department Of Medical Oncology, Henry Ford Medical Center, - - Detroit/US
  • 12 Division Of Oncology, Washington University School of Medicine, 63110 - St Louis/US
  • 13 Drug Development Department, AstraZeneca USA, 20878 - Gaithersburg/US
  • 14 Drug Development Department, AstraZeneca, - - Cambridge/GB
  • 15 Drug Development Department, AstraZeneca, - - Boston/US
  • 16 Drug Development Department, AstraZeneca, 20878 - Gaithersburg/US
  • 17 Department Of Oncology, Chaim Sheba Medical Center, 52621 - Ramat Gan/IL

Resources

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Abstract 4019

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

EndpointOverall 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)
Responses19775
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.

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