#ESMO20: AstraZeneca aims to spur PROfound shift in prostate cancer treatment with Lynparza OS data
AstraZeneca has unveiled the final, mature overall survival data that cemented Lynparza’s first approval in prostate cancer approval — touting its lead against rivals with the only PARP inhibitor to have demonstrated such benefit.
But getting the Merck-partnered drug to the right patients remains a challenge, something the companies are hoping to change with the new data cut.
The OS numbers on the subgroup with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer are similar to the first look on offer when the FDA expanded the label in May: Lynparza reduced the risk of death by 31% versus Xtandi and Zytiga. Patients on Lynparza lived a median of 19.1 months, compared to 14.7 months for the anti-androgen therapies (p = 0.0175).
As PROfound focused on the second-line setting, the patients in the trial had all progressed on prior treatment. Investigators showed up in Barcelona last year to detail the progression-free survival win; overall survival was the secondary endpoint.
While the results are more or less expected, José Baselga, AstraZeneca’s chief of cancer R&D, highlighted the fact that 66% of the patients on the control arm had crossed over to Lynparza.
“So if despite 67% crossover, which is a very high number, you see an improvement in survival, the question that we’re answering is no longer a question on whether olaparib improves survival or not — the answer is yes — but the question that we’re answering in an indirect fashion is do we need to start olaparib earlier or not,” he said. “And I think that that’s what this is telling. So I think that this becomes a very clear indication that we need to start olaparib early in the intended use as opposed to wait.”
Notably, Lynparza wasn’t just approved to treat patients with BRCA1/2 and ATM mutations; there are 12 other homologous recombination repair (HRR) gene mutations on the label. On that broader trial population, an exploratory analysis found a non-statistically significant improvement in OS, with a hazard ratio of 0.79. Median OS was 17.3 months, 3.3 months longer than the Xtandi/Zytiga arm.
It remains to be seen whether that would convince more physicians to adopt that 15-gene assay, the companion diagnostic for Lynparza in the mCRPC setting that AstraZeneca estimates would find about one in four patients eligible. The drug is, afterall, the first targeted therapy approved for this space.
Dave Fredrickson, who leads AstraZeneca’s oncology business unit, conceded that testing for HRR gene mutations beyond BRCA is “not yet sufficiently widespread.”
“In PROfound, the overall survival benefit creates an important impetus for healthcare practitioners around the globe to embrace testing; they want to ensure each patient is matched with the targeted medicine from which he will most benefit,” he wrote to Endpoints News.