Doubts about whether Lynparza’s win in the adjuvant breast cancer study Olympia was sufficiently meaningful might be swept away at Asco. Full data from Olympia, just revealed in an Asco late-breaker and published simultaneously in the NEJM, not only confirm the win on disease-free survival but also show an impressive separation of early overall survival curves.
With Lynparza already available for gBrca1/2-mutated metastatic breast cancer, the readout of Olympia could extend the Astrazeneca/Merck & Co drug’s reach into earlier settings. Since Olympia also concerned gBrca1/2 specifically, the implication is that patients should be tested for this mutation early, in pre-metastatic, operable settings.
Presenting the data an embargoed press briefing last week, Dr Andrew Tutt, from the UK’s Institute of Cancer Research, said around 5% of all breast cancers were associated with gBrca1/2 mutation. A “mindset change” among doctors was now needed regarding diagnosis, as genetic testing was perhaps not being done frequently enough.
Olympia was said in February to have crossed the boundary for its primary endpoint of invasive disease-free survival (DFS) at interim review, and thus proceeded to early analysis. Though no data were revealed at the time the win was a surprise since the study had been overhauled and delayed (Lynparza’s Olympia win could broaden breast cancer use, February 17, 2021).
Dr Tutt has now unveiled a 42% reduction in risk of invasive disease for Lynparza versus placebo, with a highly statistically significant p value below 0.0001. Not only that, but distant DFS, a secondary endpoint, was also improved with Lynparza, with a 0.57 hazard ratio (p<0.0001). Medians have not been reached for either endpoint.
While DFS data might be enough to satisfy regulators, a key question for prescribers is whether Lynparza actually helps patients live longer. Here Dr Tutt had more good news, revealing OS curves that, at 2.5 years’ median follow-up, appeared to be separating.
This separation, though only concerning 59 and 86 deaths for Lynparza and placebo respectively, translated into a 32% reduction in risk of death (p=0.02). Given what Dr Tutt called a “very stringent test required to declare statistical superiority, to save statistical power”, this p value was not significant, and follow-up will continue.
Dr Tutt stopped short of describing the Olympia data as practice changing, but did say they showed Lynparza to provide a meaningful benefit to patients for one year in the adjuvant setting, after surgery and standard therapies such as chemotherapy, hormone therapy and radiation.
It should also be stressed that patients in Olympia were ER-positive and Her2-negative; the trial had started out testing triple-negative gBrca1/2 mutants, but was later broadened.
Moderating the press conference, Dr Lori Pierce, Asco’s president, said the results might open the door to additional adjuvant trials of Parp inhibitors in other Brca1/2-associated cancers.
It should also be considered whether they might prompt testing of other Parp inhibitors specifically in adjuvant breast cancer. Remarkably, there are no ongoing industry-sponsored clinical studies beyond Olympia in this setting, and only Pfizer’s Talzenna also has metastatic breast cancer already on its label.