Docetaxel rechallenge versus cabazitaxel in patients previously treated with docetaxel for metastatic castrate-resistant prostate cancer (mCRPC).
Barata, PC; Corrigan, J; Culnan, J; Dulberger, KN; La, J; Akama-Garren, E; DuMontier, C; Hansen, JE; Bitting, RL; Cheng, HH; Cooperberg, MR ...
Published in: Journal of Clinical Oncology
In 2004, docetaxel (DOC), a semi-synthetic taxane, received regulatory approval for mCRPC based on improved overall survival (OS). Cabazitaxel (CAB), a closely related analog of DOC, was approved in 2010 for mCRPC patients previously exposed to DOC. For patients previously treated with DOC, the relative benefits of docetaxel rechallenge (rDOC) versus a taxane switch to CAB are unknown. We aimed to evaluate the relative impact of rDOC versus CAB for patients who had previously received DOC for mCRPC.
This retrospective cohort study compared outcomes of mCRPC patients in the nationwide VA healthcare system who received initial DOC, discontinued DOC for a reason other than disease progression, and later received rDOC or CAB after mCRPC diagnosis. Patients were eligible for inclusion if they received at least 3 cycles of DOC and at least 90 days later received a second course of DOC or CAB. The index date was the date of the start of the second course of taxane treatment. Time-to-event outcomes were evaluated from index date. Inverse probability of treatment weighting (IPTW) was used to control for potential confounders.
Between 1/2010 and 12/2023, a total of 669 patients (407 CAB, 262 rDOC) with median age 72, 29% Black, 27% CD, 39% CKD, 38% DM2, were included in final analysis. For the first instance of docetaxel, patients received a median of 6 (IQR: 4-10) cycles with a PSA50 = 20%, PSA90 = 3% and a median of 1 (IQR: 0-1) additional systemic treatment prior to subsequent taxane. At the time of the initiation of the second taxane, 73% of patients had bone and 18% visceral metastases and median initial PSA of 75 ng/mL. Compared to CAB, rDOC had higher PSA90 (11% vs 3%, p<0.001), longer OS (12.5 vs 9.6 months, p<0.001) and numerically longer time to next systemic treatment (16.4 vs 12.4 months, p=0.2), shorter time on treatment (2.1 vs. 2.6 months, p=0.56), and similar PSA50 (8% vs 9%, p=0.31). The use of platinum (9% vs 6%, p=0.15), immunotherapy (2 vs 1%, p=0.79) and PARP inhibitors (6% vs 5%, p=0.67) after the second instance of a taxane was not statistically different between groups.
In this study, rDOC was associated with better survival and deeper response than cabazitaxel. The findings of this large-scale study provide guidance for making well-informed decisions about sequential use of taxanes for mCRPC treatment.
