Case 2: The PROfound Trial for Olaparib in Metastatic CRPC
Mary-Ellen Taplin, MD, presents data from the phase 3 PROfound trial of olaparib in metastatic castration-resistant prostate cancer.
Mary-Ellen Taplin, MD: It’s a profound pleasure to share with you the data from the PROfound trial today. Here’s the schema of the PROfound trial. It’s notable that these are patients with metastatic castration-resistant prostate cancer [CRPC] who have progressed on either abiraterone acetate or enzalutamide but not prior chemotherapy. These patients had 1 or more of a qualifying gene abnormality, and they were cohorted into BRCA1, BRCA2, and ATM and a second cohort with a compilation of all the other alterations. Patients were randomly assigned to olaparib, which is a PARP inhibitor, or physician’s choice of therapy that’s FDA approved for mCRPC [metastatic castration-resistant prostate cancer]. The primary end point was radiographic progression-free survival, which was reviewed centrally, and there are some key secondary end points noted there.
Here is the radiographic progression-free survival by the central review for patients with a BRCA1, BRCA2, and ATM. As you can see, it was markedly positive with a hazard ratio of 0.34; 3.6 months for the control and 7.4 months for the patients who received the olaparib. Here are the same data, rPFS [radiographic progression-free survival], for the overall population. The data remain positive for the group that got olaparib with a hazard ratio of 0.49; 5.8 months for the olaparib vs 3.5 months for the control. It was recently published in the New England Journal of Medicine.
The overall survival, which was a key secondary end point, also showed positivity for olaparib for BRCA1, BRCA2, and ATM. Adjusted for the crossover, it also remained positive. You can see the number of months there, 19.1 months for the olaparib vs 14.7 months and a hazard ratio of 0.69. Here are the similar data for the overall population, with cohorts A and B similarly remaining positive with a hazard ratio of 0.79. Adjusted for crossover, there’s significant positivity there as well.
Here’s the safety summary for those of us who have used PARP inhibitors in our practice. We know that they can cause some significant adverse effects, particularly anemia and some GI [gastrointestinal] adverse effects. Here you can see some anemia particularly, more than physician’s choice, some vomiting, and a little shortness of breath perhaps related to the anemia.
I think all of you are aware of the FDA-approved olaparib for homologous recombination–deficient tumors that have progressed following treatment with abiraterone or enzalutamide.
Transcript edited for clarity.
