OlympiAD
OlympiAD was the first trial to show a PARP inhibitor tablet beats chemotherapy in breast cancer, delaying progression by about three months in women with an inherited BRCA mutation and with fewer side effects, though it did not lengthen life overall.
Overview
OlympiAD, trial NCT02000622 sponsored by AstraZeneca and published in the New England Journal of Medicine in 2017, randomised 302 patients with a germline BRCA1 or BRCA2 mutation and HER2-negative metastatic breast cancer, about half triple-negative, to olaparib tablets or the physician's choice of capecitabine, eribulin or vinorelbine. Progression-free survival rose from 4.2 to 7.0 months (hazard ratio 0.58), the response rate doubled and severe side effects were less common with olaparib; overall survival was 19.3 against 17.1 months and not significantly different, with a suggestion of benefit in patients who had not had chemotherapy for metastatic disease. It led to the January 2018 approval of olaparib, the first PARP inhibitor for breast cancer, and made germline testing a treatment decision in metastatic disease. Whether PARP inhibition should come before or after platinum, to which it shares a mechanism of resistance, is the open question.
- Median 7 vs 4.2 months with Olaparib compared with Chemotherapy; about 2.8 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 42 percent lower chance of the event at any given time (hazard ratio 0.58, likely range 0.43 to 0.8).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- Median 19.3 vs 17.1 months with Olaparib compared with Chemotherapy; about 2.2 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 10 percent lower chance of the event at any given time (hazard ratio 0.9, likely range 0.66 to 1.23).
- The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- These results apply to the people the trial enrolled: Germline BRCA-mutated, HER2-negative metastatic breast cancer after up to two chemotherapy lines: olaparib vs physician's choice chemotherapy. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (BRCA); the result should not be assumed for people whose cancer does not have it.
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.
302 participants enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Olaparib | 205 | 7 months | 0.58 (0.43 to 0.8) | <0.001 | link |
| Chemotherapy | 97 | 4.2 months | ||||
| Overall survival | Olaparib | - | 19.3 months | 0.9 (0.66 to 1.23) | - | link |
| Chemotherapy | - | 17.1 months |
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