Real-world Characteristics and Outcomes of Patients With Metastatic Castration-resistant Prostate Cancer Receiving Chemotherapy Versus Androgen Receptor-targeted Therapy After Failure of First-line Androgen Receptor-targeted Therapy in the Community Setting

Optimal treatment sequences for metastatic castration-resistant prostate cancer are unknown. This retrospective study assessed outcomes in patients with metastatic castration-resistant prostate cancer receiving second-line taxane chemotherapy versus second-line androgen receptor-targeted therapy (ART), after failure of first-line ART, in a real-world setting. In patients who have previously recieved ART, second-line taxane chemotherapy, versus alternative ART, may be associated with improved outcomes, particularly among patients with a worse disease prognosis. Background: In metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequences are unknown. We assessed second-line taxane (TT) versus androgen receptor-targeted therapy (ART), after initial ART failure, in United States oncology community practices. Patients and Methods: Using electronic medical records, patients with mCRPC receiving first-line ART and second-line therapy (TT, ART) were identified. Response and overall survival (OS) were evaluated from second-line therapy initiation. Multivariate analyses were adjusted for year, age, metastases, opioid use, prostate-specific antigen (PSA), hemoglobin, alkaline phosphatase, and albumin levels. Results: Of 546 patients receiving first-line ART, 206 and 340 received second-line TT and ART. Compared with patients receiving second-line ART, patients receiving TT were younger (median, 74 vs. 79 years), more had intermediate-high Halabi risk scores (59% vs. 35%), had higher opioid use (42% vs. 22%), median PSA (116 vs. 48 ng/mL), alkaline phosphatase (112 vs. 87 U/L), and lactate dehydrogenase (254 vs. 201 U/L), and had lower hemoglobin (11.2 vs. 12.3 g/dL) and albumin levels (3.8 vs. 4.0 g/dL); all P <.001. Response rates were higher with second-line TT versus ART (clinical response, 44.2% vs. 24.7%; P =.006; PSA response, 44.5% vs. 28.7%; P =.004). OS did not differ between cohorts (hazard ratio [HR], 0.90; P =.511). Among patients with a poor prognosis (hemoglobin < 11 g/d; albumin < lower limit of normal), those receiving second-line TT versus ART showed improved OS (HR, 0.52; P =.004 and HR, 0.36; P =.003, respectively). Conclusions: Despite more severe disease profiles, patients with mCRPC receiving second-line TT versus ART achieved higher response rates after initial ART. Poor prognosis patients had improved OS with second-line TT versus ART.