Is Adding Palbociclib to Androgen-Deprivation Therapy of Benefit in Prostate Cancer?
Posted: Thursday, May 6, 2021
Maha Hussain, MD, of Northwestern University/Robert H. Lurie Comprehensive Cancer Center, Chicago, and colleagues hypothesized that co-targeting the cell-cycle and androgen receptors with palbociclib might improve outcomes in patients with retinoblastoma-intact metastatic hormone-sensitive prostate cancer. However, based on their phase II study findings published in Clinical Cancer Research, the addition of the CDK4/6 inhibitor did not seem to improve outcomes.
Of 72 patients with retinoblastoma-intact metastatic hormone-sensitive prostate cancer, 60 were enrolled to initiate therapy. Participants were randomly assigned 1:2 to receive either androgen-deprivation therapy alone (arm 1) or palbociclib plus androgen-deprivation therapy (arm 2). Exome sequencing was performed on tumors based on availability, and circulating tumor cells were counted at multiple points during treatment.
No adverse events greater than grade 2 were observed in arm 1. Grade 3 to 4 adverse events affected 58% of patients in arm 2, and 48% were hematologic; the most common side effect was neutropenia (40%). Grade 3 decreased white blood cell count was identified in five patients.
Prostate-specific antigen levels of at most 4 ng/mL were reached by 80% of all participants at 28 weeks. Undetectable levels at 28 weeks were achieved by 50% of patients in arm 1 and 43% in arm 2. The rate of biochemical progression-free survival was 69% and 74% in arms 1 and 2, respectively, suggesting no significant prostate-specific antigen delay or clinical benefit with the addition of palbociclib.
In both arms, the radiographic response rate was 89%. Blood samples at disease progression demonstrated a statistically significant increase in circulating tumor cell count, but there was no significant difference between the cohorts at any point. Based on molecular data from biopsies, TP53, PI3K pathway mutations, and 8q gain seemed to correlate with a shorter time to biochemical disease progression, as well as poor outcome.
Disclosure: The study authors reported no conflicts of interest.
