Gemcitabine/nab‐paclitaxel vs gemcitabine/carboplatin for advanced urothelial carcinoma

• Published in: BJU international Vol. 134; no. 1; pp. 63 - 71
• Main Authors: An, Xin, Xue, Cong, Chen, Meiting, Ni, Mengqian, Ma, Huali, Tian, Li, Huang, Riqing, Li, Xiangdong, Ye, Yunlin, Qin, Tao, Dong, Pei, Li, Zhiyong, Peng, Jing, Yao, Kai, Zhou, Fangjian, Liu, Zhuowei, Shi, Yanxia
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2024
• Subjects: Aged; Aged, 80 and over; Albumins - administration & dosage; Albumins - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin; Carboplatin - administration & dosage; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - pathology; Cisplatin; cisplatin‐ineligible; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease control; Female; first‐line; Gemcitabine; Humans; Male; Metastases; metastatic urothelial carcinoma; Middle Aged; nab‐paclitaxel; Nanoparticles; Neuropathy; Paclitaxel; Paclitaxel - administration & dosage; Peripheral neuropathy; Progression-Free Survival; Thrombocytopenia; Treatment Outcome; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Urologic Neoplasms - drug therapy; Urologic Neoplasms - pathology; Urological cancer; Urothelial cancer; Urothelial carcinoma; first‐line; gemcitabine; nab‐paclitaxel; carboplatin; metastatic urothelial carcinoma; cisplatin‐ineligible
• ISSN: 1464-4096; 1464-410X; 1464-410X
• DOI: 10.1111/bju.16241

Objective To compare in a phase III trial the efficacy and safety of nanoparticle albumin‐bound (nab)‐paclitaxel plus gemcitabine (GA) with that of carboplatin plus gemcitabine (GCb) as a first‐line treatment for patients with cisplatin‐ineligible metastatic urothelial cancer (mUC). Patients and Methods Treatment‐naive, cisplatin‐ineligible patients with mUC were assigned randomly to either the GA (both nab‐paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on Days 1 and 8, every 21 days) or GCb group (carboplatin area under the free carboplatin plasma concentration versus time curve of 4.5 on Day 1, gemcitabine 1000 mg/m2 on Days 1 and 8, every 21 days). The primary endpoint was progression‐free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and patient‐reported outcomes (PROs). Results The trial was terminated early because of slow accrual after 54 patients were enrolled: 26 in in the GA group and 28 in the GCb groups. The median PFS was 6.7 vs 5.9 months for the GA and GCb groups, respectively (P = 0.248). The median OS time was 12.1 vs 10.7 months for the GA and GCb groups, respectively (P = 0.837). The ORR and DCR were 40% vs 46.4% (P = 0.637) and 72% vs 68% (P = 0.188) in the GA and GCb groups, respectively. Patients treated with GA showed significantly lower incidence of Grade 3–4 thrombocytopenia and does reduction and delay. Although peripheral sensory neuropathy was higher in the GA arm, no Grade 3 neuropathy occurred. There was no difference in the PROs between the two groups. Conclusion While not powered for comparison, first‐line GA showed similar efficacy and better tolerability and might be considered a rational alternative to GCb.