Dr McKay on the Safety of Olaparib and Radium-223 in mCRPC With Bone Metastases

"With regards to the safety analysis, we [saw] increased grade 3 and 4 toxicity with the combination compared with the radium monotherapy. We saw slightly increased rates of anemia, with 16.3% of patients experiencing grade 3 or higher anemia in the radium-223 monotherapy arm compared with 22.0% in the combination treatment arm. Additionally, we observed an increased rate of lymphopenia—31.0% in the [combination] arm vs 9.1% in the radium-223 [monotherapy] arm."

Rana R. McKay, MD, FASCO, a medical oncologist and professor of medicine and urology at the University of California, San Diego, discussed safety outcomes from the phase 2 COMRADE trial (NCT03317392), a multicenter, randomized, investigator-initiated study conducted within the National Cancer Institute. The study evaluated the combination of olaparib (Lynparza) and radium-223 (Xofigo) compared with radium-223 monotherapy in men with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases.

In this trial, patients were randomly assigned to receive either radium-223 alone or in combination with olaparib to assess whether the addition of the PARP inhibitor would improve clinical outcomes without compromising tolerability. McKay noted that the primary safety analysis demonstrated increased rates of grade 3 or higher adverse effects with the combination regimen compared with the monotherapy.

Specifically, grade 3 or higher anemia was reported in 22.0% of patients treated with the combination of olaparib plus radium-223 compared with 16.3% of patients in the radium-223 monotherapy arm. McKay also highlighted a notable difference in the incidence of grade 3 or higher lymphopenia, which was observed in 31.0% of patients in the combination arm vs 9.1% of those in the monotherapy group. This disparity in lymphopenia was identified as the main driver of the observed increase in high-grade toxicity between the treatment arms, according to McKay.

Despite the elevated hematologic toxicity, McKay stated that the combination regimen was otherwise well tolerated. The reduced dose of olaparib likely contributed to the manageable tolerability observed in the trial population, she concluded.