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Poster Display session 2

3340 - Effectiveness of Olaparib Plus Trastuzumab in HER2[+], BRCA–mutated (BRCAm) or Homologous Recombination Deficient (HRD) Advanced Breast Cancer (ABC) patients (pts). The OPHELIA Study


29 Sep 2019


Poster Display session 2


Tumour Site

Breast Cancer


José Enrique Alés-Martínez


Annals of Oncology (2019) 30 (suppl_5): v104-v142. 10.1093/annonc/mdz242


J.E. Alés-Martínez1, S. Morales2, M. Fernández Abad3, P. Sánchez-Rovira4, F.J. Salvador Bofill5, A. Lahuerta6, J.A. García-Sáenz7, I. Garau Llinas8, T. Díaz Redondo9, N. Ferrer10, V. Carañana11, R. López12, S.E. Alonso Soler13, B. Bermejo14, J. de la Haba15, P. Zamora16, J. Balmana17, E. López-Miranda18, J. Cortés19, A. Llombart Cussac20

Author affiliations

  • 1 Medical Oncology, Hospital Nuestra Señora de Sonsoles, 05004 - Ávila/ES
  • 2 Medical Oncology, Hospital Universitari Arnau de Vilanova de Lleida, 25198 - Lleida/ES
  • 3 Medical Oncology, Hospital Universitario Ramón y Cajal, 28034 - Madrid/ES
  • 4 Medical Oncology, Complejo Hospitalario de Jaén, 23007 - Jaén/ES
  • 5 Medical Oncology, Hospital Universitario Virgen del Rocío, 41013 - Sevilla/ES
  • 6 Medical Oncology, Fundación Onkologikoa, 20014 - Donostia-San Sebastián/ES
  • 7 Medical Oncology, Hospital Clínico San Carlos, 28040 - Madrid/ES
  • 8 Medical Oncology, Hospital Son Llatzer, 07198 - Palma de Mallorca/ES
  • 9 Medical Oncology, Hospital Universitario Virgen de la Victoria, 29010 - Malaga/ES
  • 10 Medical Oncology, Hospital Universitari Son Espases, 07120 - Palma de Mallorca/ES
  • 11 Medical Oncology, FISABIO, Hospital Arnau de Vilanova, 46015 - Valencia/ES
  • 12 Medical Oncology, Hospital Clínico Universitario de Santiago (CHUS), 15706 - Santiago de Compostela/ES
  • 13 Medical Oncology, Hospital San Pedro de Alcántara, 10003 - Cáceres/ES
  • 14 Medical Oncology, Hospital Clínic Universitari de València, 46010 - Valencia/ES
  • 15 Medical Oncology, Hospital Universitario Reina Sofía, 14004 - Córdoba/ES
  • 16 Medical Oncology, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 17 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 18 Medical Oncology, Medica Scientia Innovation Research (MedSIR), Ridgewood, New Jersey, USA & Barcelona, Spain; Hospital Universitario Ramón y Cajal, 28034 - Madrid/ES
  • 19 Medical Oncology, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain; IOB Institute of Oncology, Quironsalud Group, Madrid and Barcelona, Spain; Medica Scientia Innovation Research (MedSIR), Ridgewood, New Jersey, USA, 08035 - & Barcelona/ES
  • 20 Medical Oncology, Medica Scientia Innovation Research (MedSIR), Ridgewood, New Jersey, USA & Barcelona, Spain; FISABIO, Hospital Arnau de Vilanova, 46015 - Valencia/ES


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Abstract 3340


In the OlympiAD trial the use of poly(adenosine diphosphate–ribose) polymerase inhibitor (PARPi) olaparib resulted in better progression–free survival (PFS) than standard chemotherapy, which led to approval in germinal BRCAm (gBRCAm)/HER2[-] ABC pts. There is a potential therapeutic role for PARPis in pts with defective DNA repair. Preclinical data support a strong synergism with trastuzumab in HER2[+] cells that are sensitive to PARPis. This study will evaluate the efficacy and safety of olaparib plus trastuzumab in HER2[+] gBRCAm or wild–type gBRCA/HRD ABC pts.

Trial design

This is a multicenter, single–arm, two–cohort, Simon’s two–stage, phase II trial. The cohort A will recruit N = 20 gBRCAm ABC pts. The cohort B will recruit N = 13 wild–type gBRCA/HRD ABC pts based on HRDetect assay. Pts will receive olaparib (300mg p.o. b.i.d. during 21–day cycles) in combination with trastuzumab (IV/SC at standard dose) until progression or unacceptable toxicity. Main selection criteria: (1) Pre– and post–menopausal women with HER2[+] ABC; (2) ≤3 prior regimens of chemotherapy and/or trastuzumab–lapatinib in advanced setting, and at least 1 regimen of chemotherapy including trastuzumab; (3) Pts treated with carboplatin or platinum compounds in the last 12 months are not eligible; (4) Evaluable or measurable disease. Co–Primary objectives: Overall response rate (ORR) and PFS of olaparib plus trastuzumab in the cohort A. In the cohort A (N = 20), we plan a Simon’s two–stage design (7 pts in the 1st stage and 13 pts in the 2nd stage in case of any responder in 1st stage). Final ORR will be promising with ≥4 responders among 18 evaluable pts (H0: ORR≤5%; HA: ORR≥30%). PFS estimation will be based a one–arm log–rank test (H0: PFS≤3–months; HA: PFS≥6–months). These give us an 80% power at 0.025 one–sided alpha level. In the cohort B (N = 13) ORR will be promising with ≥3 responders among 13 pts (p < 0.025; H0: ORR≤5%). Secondary objectives: Safety–related outcomes, clinical benefit rate, overall survival, and quality of life. Exploratory objectives: Prevalence of gBRCAm and HRD in HER2[+] ABC, and identification of new potential predictive markers.

Clinical trial identification

NCT03931551. First Posted: April 30, 2019.

Editorial acknowledgement

Legal entity responsible for the study

Medica Scientia Innovation Research (MedSIR); Experior.


AstraZeneca Famacéutica Spain S.A.


J.A. García-Sáenz: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis, Celgene, Eli Lilly, EISAI, Roche; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Novartis, Roche, Pfizer. J. Balmana: Advisory / Consultancy: AstraZeneca, Pfizer. E. López-Miranda: Full / Part-time employment: Medica Scientia Innovation Research (MedSIR). J. Cortés: Advisory / Consultancy: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex; Honoraria (institution): Roche, Novartis, Celgene, Eisai, Pfizer, Samsung; Research grant / Funding (institution): Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Medica Scientia Innovation Research (MedSIR). A. Llombart Cussac: Honoraria (institution), Advisory / Consultancy: Roche, GlaxoSmithKline, Novartis, Celgene, Eisai, AstraZeneca; Research grant / Funding (institution): GlaxoSmithKline, Sanofi, Puma Biotechnology; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Medica Scientia Innovation Research (MedSIR). All other authors have declared no conflicts of interest.

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