See the results of the PROfound trial presented at ESMO Virtual Congress 2020, whose updates of global survival data were published in the New England Journal of Medicine
In this phase III randomized trial, patients with castration-resistant metastatic prostate cancer who used enzalutamide, abiraterone or both (hormonal agents) were selected. The trial opened two follow-up cohorts according to mutations in the genes BRCA1, BRCA2 or ATM (Cohort A) and BARD1, CDK12, CHEK1, CHEk2, etc (Cohort B). The patients were randomly distributed in a 2: 1 ratio in two arms: one arm that received olaparib and another in which they maintained the hormone treatment of choice of the investigating physician. The primary endpoint was progression-free survival assessed by image.
The results confirmed an increase in radiological progression-free survival of 7.4 months in the olaparib group versus 3.6 months in the control group. The hazard ratio between the therapeutic and control groups was 0.34.
The updated overall survival in cohort A was 19.1 months in the olaparib group and 14.7 months in the control group (hazard ratio 0.69). Of all the patients in the control group, 66% who had progression crossed over into olaparib group. In an adjusted analysis disregarding the crossing, the adjusted hazard ratio of overall survival was 0.42. An overall benefit of olaparib on radiological progression-free survival was observed in all cohorts.
Among the main side effects observed, nausea and anemia stand out in the treatment with olaparib.
In male patients who experienced progression even in the presence of hormonal inhibitors such as enzalutamide and abiraterone and who had mutations in genes associated with homologous recombination repair, the use of olaparib was associated with a higher progression-free survival and better response rates and patient-dependent endpoints than those derived from the action of enzalutamide or abiraterone.
de Bono J, Mateo J, Fizazi K, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020;382(22):2091-2102. doi: 10.1056 / NEJMoa1911440
610O – Final overall survival (OS) analysis of the PROfound: Olaparib vs physician”s choice of enzalutamide or abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC), and homologous recombination repair (HRR) gene alterations