Efficacy and safety of nanosomal docetaxel lipid suspension in Indian patients with metastatic castration-resistant prostate cancer (mCRPC): A multicenter, open-label, single-arm phase 4 study.

168 Background: Docetaxel combined with prednisone is the first line chemotherapy to improve overall survival in metastatic castration resistant prostate cancer (mCRPC). Nanosomal docetaxel lipid suspension (NDLS) is a novel formulation that eliminates the need for polysorbate 80 and ethanol, reducing infusion-related reactions and the requirement for steroid premedication. This phase 4 trial aims to assess the efficacy and safety of NDLS in patients with mCRPC. Methods: In this multicenter, open-label, single-arm trial, patients with confirmed mCRPC and at least one measurable lesion were enrolled. Exclusions included those with brain lesions or a history of hypersensitivity to taxanes. NDLS was administered at 75 mg/m 2 every three weeks for 10 cycles without steroid premedication. The primary endpoint was the overall response rate (ORR) upon completion of 10 cycles. Results: Between July 2018 and July 2023, 86 patients (safety set) received the study drug. The modified intention-to-treat (mITT) set (included 77 patients who received at least one dose and had at least one efficacy evaluation). The mean age of the mITT set was 67 (±6.2) years, with a median prostate specific antigen (PSA) value of 31.3 ng/mL. At the end of 10 cycles, the overall response rate (ORR) was 16.9% (95% CI: 9.31, 27.14), and the disease control rate (DCR) was 44.2% (95% CI: 32.84, 55.93). A ≥50% reduction in serum PSA was observed in 36 (46.8%) patients. The visual analog score (VAS) decreased significantly from baseline with a mean difference of 12.8 mm (P<0.0001). Median progression free survival (PFS) was 12 months (95% CI: 8.12, 18.12), and the overall survival rates at 1 and 2 years were 31.2% and 19.5% respectively. Adverse events were reported in 64 (84.4%) patients, with only one patient experiencing a grade ≥3 adverse event. Common grade 1/2 adverse events (≥10% of patients) included diarrhea, vomiting, asthenia, alopecia, headache, anemia, fever, infections, and pain. Conclusions: NDLS showed efficacy and safety in patients with metastatic castration-resistant prostate cancer. Clinical trial information: CTRI/2018/02/012212 . Efficacy outcomes at cycle 10 completion. Parameter mITT set (N=77) PR, n (%) 13 (16.9) SD, n (%) 21 (27.3) ORR, (95% CI) 16.9% (9.31, 27.14) DCR, (95% CI) 44.2% (32.84, 55.93) BOR, (95% CI) 26.0% (16.64, 37.23) ≥50% reduction in serum PSA, n (%) 36 (46.8) Change from baseline for VAS (mm), mean (±SD) 12.8 (±22.11) (p<0.0001) Median PFS (months), (95% CI) 12 (8.12, 18.12) Median OS (months) Not reached PR: partial response; SD: stable disease; BOR: Best overall response.