Dr McKay on Data for Olaparib Plus Radium-223 in CRPC With Bone Metastases

"This was a positive trial, resulting in a statistically significant improvement in radiographic progression-free survival [rPFS] with the combination compared to radium-223 alone. The rPFS in the [experimental] treatment arm was 8.9 months compared to 4.7 months in the control arm, with a hazard ratio of 0.47, which was statistically significant."

Rana R. McKay, MD, FASCO, a medical oncologist and professor of medicine and urology at UC San Diego, discussed initial results from the phase 2 COMRADE trial (NCT03317392), a multicenter, randomized, investigator-initiated ETCTN study evaluating the combination of olaparib (Lynparza) and radium-223 (Xofigo) vs radium-223 monotherapy in men with castration-resistant prostate cancer (CRPC) with bone metastases.

The trial's primary efficacy end point was radiographic progression-free survival (rPFS), and the trial also incorporated exploratory biomarker analyses, including the assessment of homologous recombination repair (HRR) alterations via circulating tumor DNA (ctDNA).

Findings from the study presented at the 2025 ASCO Annual Meeting demonstrated a statistically significant improvement in rPFS in the combination arm compared with the control arm. In patients treated with olaparib plus radium-223 (n = 61), the median rPFS was 8.9 months compared with 4.7 months in those receiving radium-223 alone (HR, 0.47; 90% CI, 0.34-0.65; 1-sided P = .0013).

Further subgroup analyses indicated that the treatment benefit was most pronounced in patients who had not received prior therapy with docetaxel (HR, 0.24; 90% CI, 0.15-0.40) vs those who had received prior docetaxel (HR, 0.73; 90% CI, 0.48-1.11). Those 20 or fewer bone metastases experienced a more pronounced benefit with the combination (HR, 0.21; 90% CI, 0.13-0.33) compared with patients who had more than 20 bone metastases (HR, 1.17; 90% CI, 0.75-1.84).

In an exploratory analysis based on ctDNA, patients who did not harbor HRR alterations, the combination treatment appeared to confer a greater benefit in terms of rPFS (HR, 0.49; 90% CI, 0.34-0.71) vs the HRR-positive population (HR, 0.47; 90% CI, 0.22-1.01).