Real-world outcomes of cabazitaxel plus carboplatin versus cabazitaxel alone in metastatic castration-resistant prostate cancer.

e17044 Background: Cabazitaxel is an established treatment for metastatic castration-resistant prostate cancer (mCRPC). In real-world practice, carboplatin is often added for aggressive disease phenotypes despite limited comparative effectiveness data. We evaluated the real-world effectiveness and safety of cabazitaxel plus carboplatin versus cabazitaxel alone. Methods: We conducted a retrospective comparative effectiveness study using the TriNetX US Collaborative Network, including data from 69 U.S. healthcare organizations. Adult men (≥18 years) with mCRPC treated with cabazitaxel were identified and categorized into cabazitaxel plus carboplatin or cabazitaxel alone cohorts. The index date was defined as first exposure to cabazitaxel, with outcomes assessed from 90 days post-index. Patients with hematologic malignancies were excluded. Propensity score matching (1:1) was performed using demographics and key comorbidities. Outcomes included PSA response, all-cause mortality, treatment-related toxicities, and healthcare utilization. Results: After propensity score matching, 1,618 patients were included (809 per cohort), with a median age at index of 68 years in both groups. The matched population was racially and ethnically similar between cohorts, comprising approximately 74% White patients, 15% Black or African American patients, and 7% Hispanic or Latino patients (approximately 81% non-Hispanic). Baseline comorbidity burden was comparable after matching, including hypertension (~62%), chronic kidney disease (~14%), and heart failure (~7%) (all p > 0.05). Patients treated with cabazitaxel plus carboplatin were significantly more likely to achieve a deep biochemical response, defined as PSA < 4 ng/mL, compared with cabazitaxel alone (14.5% vs 9.5%; risk ratio 1.52; p = 0.002). In contrast, rates of partial PSA response (PSA 4–20 ng/mL) were similar between groups (19.2% vs 17.3%; p = 0.33), indicating that the PSA benefit was driven by deeper PSA suppression rather than modest PSA reductions. All-cause mortality was comparable between cohorts (65.4% vs 65.5%), with no significant difference in overall survival. Combination therapy was associated with higher rates of hematologic toxicity, including bone marrow suppression (54.0% vs 45.0%; p < 0.001), anemia (71.7% vs 65.4%; p = 0.006), and thrombocytopenia (33.6% vs 26.0%; p = 0.001). Rates of fatigue (41.8% vs 39.7%), hospital admissions (44.6% vs 42.8%), and analgesic utilization (90.5% vs 89.0%) were similar between treatment groups. Conclusions: In this large real-world cohort, adding carboplatin to cabazitaxel was associated with higher rates of deep PSA response but no overall survival benefit and increased hematologic toxicity. These findings highlight the need for improved patient selection and prospective studies to clarify the clinical role of this combination in mCRPC.