ASCO Plenary: PARPi prevents disease recurrence in BRCA-mutated high-risk, early stage breast cancer

• Full results from the OlympiA Phase III, multicenter trial promise to extend the use of PARPi olaparib as adjuvant therapy for patients with early-stage, high-risk breast cancer with a germline BRCA mutation.

• Reflecting the relevance of this potentially practice-changing study, these data were selected to first outing during a Plenary Session at the American Society of Clinical Oncology’s (ASCO), 2021 Virtual Annual Meeting, 04 – 08 June.

• Driven through a global academic and industry partnership, including VHIO, OlympiA opens up a new treatment avenue to prevent disease recurrence for these patients.

Barcelona, June 3, 2021 –

In the quest to establish more potent treatment strategies that target vulnerabilities in BRCA1/2-associated cancers, PARP inhibitor (PARPi) olaparib (Lynparza®) continues to drive more precise and personalized therapeutic approaches. By prolonging survival and reducing risk of disease progression, this anti-cancer therapy has been approved for the treatment of both BRCA1/2 mutated advanced breast and ovarian cancers, and is also licensed as maintenance therapy after response to platinum-based chemotherapy for the latter.

Over the past two decades, the development and regulatory approval of an array of more personalized and targeted therapies against breast cancer continue to significantly improve outcomes for patients. However, an estimated 2.3 million women were diagnosed with this disease worldwide in 2020 ⁽¹⁾. As the most common cancer among women globally, the vast majority of breast cancer cases are diagnosed at an early stage.

BRCA mutations are found in approximately 5% of breast cancer patients. Around 55-65% of women with a BRCA1 mutation, and approximately 45% with a BRCA2 mutation will develop breast cancer before the age of 70 ⁽²⁾. Despite advances in treatment, many patients with high-risk disease will unfortunately develop a recurrence.

Responding to these trends, the OlympiA interventional Phase III study ⁽³⁾, directed by Andrew Tutt, Institute of Cancer Research and Kings College London (UK), aimed at extending the personalized and targeted promise of olaparib to patients with early-stage, primary, high-risk HER2-negative breast cancer and a germline BRCA1/2 mutation (gBRCAm), to improve clinical outcomes as well as prevent disease recurrence.

OlympiA is an active, double-blind, randomized trial (1:1) which enrolled 1836 patients with high-risk HER2-negative breast cancer and gBRCAm to receive adjuvant therapy with olaparib or placebo for 12 months. Randomisation was stratified by hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC), prior neoadjuvant versus adjuvant chemotherapy, and prior platinum use for breast cancer.

Selected to first outing during a Plenary Session ⁽⁴⁾ at the American Society of Clinical Oncology’s (ASCO), 2021 Virtual Annual Meeting, 04 – 08 June, and publish simultaneously in The New England Journal of Medicine ⁽⁵⁾, data showed that targeted treatment with olaparib achieved a superior 40% reduced risk of disease recurrence compared with the control group. Efficacy assessment of results obtained upon 3.5 years’ follow-up showed a 7% absolute risk reduction of distant relapse in patients treated with olaparib, compared with placebo.

 

Judith Balmaña, Principal Investigator of VHIO’s Hereditary Cancer Genetics Group, member of the SOLTI academic research group, an OlympiA Steering Committee member, investigator and co-author of this present study observed, “Regarding the recurrence of invasive disease, analysis at three years revealed that 77% of patients in the placebo arm and 86% of those receiving olaparib showed no relapse. Furthermore, as an orally administered therapy with low-level toxicity, this agent promises an improved quality of life for these patients.”  She continued, “Showing that patients with early-stage high-risk breast cancer with a germline BRCA1/2 mutation can be more effectively treated with targeted therapy, and also signposting greater opportunities for cure, these results are potentially practice-changing.”

 

“Previous results presented during last year’s ASCO 2020 Virtual Annual Meeting ⁽⁶⁾, also co-authored by Judith Balmaña, evidenced the efficacy and safety of olaparib as monotherapy in HER2-negative gBRCA-mutated metastatic breast cancer. Data from this present, major International study point to a new, more effective treatment strategy using olaparib for patients with early-stage disease towards cure,” concluded Cristina Saura, Principal Investigator of VHIO’s Breast Cancer Group.

 

Supported by NRG Oncology and AstraZeneca, the OlympiA trial is powered by a major   global academic and industry collaborative partnership between the Breast International Group, NRG Oncology, the US National Cancer Institute (NCI), Frontier Science & Technology Research Foundation (FSTRF), Astra Zeneca, Myriad Genetics Laboratories, Inc., Br.E.A.S.T. – Data Center & Operational Office at the Institut Jules Bordet, and Merck Sharp & Dohme Inc.

References

1. GLOBOCAN. Breast Cancer. December 2020: https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf.
2. National Breast Cancer Foundation. BRCA: The Breast Cancer Gene. Available at https://www.nationalbreastcancer.org/what-is-brca.
3. Randomised, Double-blind, Parallel Group, Placebo-controlled Multi-centre Phase III Study to Assess the Efficacy and Safety of Olaparib Versus Placebo as Adjuvant Treatment in Patients With gBRCA1/2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy. NCT02032823.
4. Virtual 2021 ASCO Annual Meeting, 04-08 June: Plenary Session, Sunday, June 06, 19:00h – 22:00h CEST. LBA1: OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer.
5. A.N.J. Tutt, J.E. Garber, B. Kaufman, G. Viale, D. Fumagalli, P. Rastogi, R.D. Gelber, E. de Azambuja, A. Fielding, J. Balmaña, S.M. Domchek, K.A. Gelmon, S.J. Hollingsworth, L.A. Korde, B. Linderholm, H. Bandos, E. Senkus, J.M. Suga, Z. Shao, A.W. Pippas, Z. Nowecki, T. Huzarski, P.A. Ganz, P.C. Lucas, N. Baker, S. Loibl, R. McConnell, M. Piccart, R. Schmutzler, G.G. Steger, J.P. Costantino, A. Arahmani, N. Wolmark, E. McFadden, V. Karantza, S.R. Lakhani, G. Yothers, C. Campbell, and C.E. Geyer, Jr. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. The New England Journal of Medicine. June 2, 2021. DOI:10.1056/NEJMoa2105215
6. Real-world clinical effectiveness and safety of olaparib monotherapy in HER2-negative gBRCA-mutated metastatic breast cancer: Phase IIIb LUCY interim analysis. Gelmon KA, Fasching PA, Couch F, Balmana Gelpi J, S Delaloge S,  Labidi-Galy I,  Bennett J,  McCutcheon S, Ano S, O’Shaughnessy J. DOI: 10.1200/JCO.2020.38.15_suppl.1087 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 1087-1087.