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Showed that a year of a PARP inhibitor after standard treatment improves survival in women with inherited BRCA mutations.
OlympiA, trial NCT02032823 sponsored by AstraZeneca, NRG Oncology and the Breast International Group and published in the New England Journal of Medicine in 2021, showed that a year of the PARP inhibitor olaparib after standard treatment improves survival in women with germline BRCA mutations and high-risk, HER2-negative early breast cancer, about eighty percent of whom had triple-negative disease. It randomised 1,836 patients to olaparib or placebo, met its primary invasive disease-free survival endpoint and showed an overall survival benefit that was sustained at six years. It makes germline testing a treatment decision for every such patient, and whether the benefit extends to somatic or non-BRCA HRD alterations is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
1,837 enrolled.
Step lines join published landmark estimates; the true curve between them is not shown.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Invasive disease-free survival at 3 yearsprimary | Olaparib | 921 | 85.9% | 0.58 (0.41 to 0.82) | <0.001 | link |
| Placebo | 915 | 77.1% | ||||
| Overall survival at 4 years | Olaparib | - | 89.8% | 0.68 (0.47 to 0.97) | 0.009 | link |
| Placebo | - | 86.4% | ||||
| Overall survival at 6 years | Olaparib | - | 87.5% | 0.72 (0.56 to 0.93) | - | link |
| Placebo | - | 83.2% |
Answers the two questions that hung over adjuvant olaparib, durability and late leukaemia, in its favour; the remaining question is whether carriers who also received pembrolizumab or capecitabine, whom the trial did not study, get the same benefit.
This is the European standard the UK page for triple-negative breast cancer is compared against; NICE guidance covers the same ground with a narrower set of funded drugs.
The survival result that moved adjuvant olaparib from a disease-free survival approval to an undisputed standard, and the reason germline testing at diagnosis of triple-negative breast cancer is now a treatment decision rather than a family history exercise.
Everyone with HER2-negative early breast cancer that meets high-risk criteria should be offered germline BRCA testing, because a positive result now changes treatment: a year of olaparib after chemotherapy reduces relapse and death. It does not apply to low-risk tumours, HER2-positive disease, or somatic-only BRCA mutations.
Sets the surgical and systemic rules for the one in nine to one in six triple-negative patients who carry a germline BRCA variant (11 to 17 percent by cohort); the adjuvant gap it named was filled by OlympiA the following year.
Shares Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline, BRCA-associated triple-negative breast cancer, Germline BRCA mutation (gBRCA), PARP inhibitors.
Shares Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline, BRCA-associated triple-negative breast cancer, Germline BRCA mutation (gBRCA), PARP inhibitors.
Shares Judy E. Garber, Inherited risk is mostly unidentified, PARP inhibitors, BRCA1 / BRCA2 (HRD).
Shares A UK audit of trial access and germline testing uptake in triple-negative breast cancer, Inherited risk is mostly unidentified, BRCA1 / BRCA2 (HRD), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem.
Shares Andrew Tutt, PARP inhibitors, Olaparib, BRCA1 / BRCA2 (HRD).
Shares BRCA-associated triple-negative breast cancer, PARP inhibitors, Olaparib, BRCA1 / BRCA2 (HRD).
Shares Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline, BRCA-associated triple-negative breast cancer, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line, Male breast cancer.
Shares Andrew Tutt, Germline BRCA mutation (gBRCA), BRCA1 / BRCA2 (HRD), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem.