Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
UAB Comprehensive Cancer Center, Birmingham.
Ann Oncol. 2016 Jan;27(1):49-61. doi: 10.1093/annonc/mdv509. Epub 2015 Oct 20.
The efficacy and safety of a combination of chemotherapeutic agent compared with single-agent chemotherapy in the second-line setting of advanced urothelial carcinoma (UC) are unclear. We aimed to study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced UC.
Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after platinum-based chemotherapy. Random-effects models were used to pool trial-level data according to treatment arm, including median progression-free survival (PFS), overall survival (OS), objective response rate (ORR) probability, and grade 3-4 toxicity. Univariable and multivariable analyses, including sensitivity analyses, were carried out, adjusting for the percent of patients with ECOG performance status ≥1 and hepatic metastases.
Forty-six arms of trials including 1910 patients were selected: 22 arms with single agent (n = 1202) and 24 arms with doublets (n = 708). The pooled ORR with single agents was 14.2% [95% confidence interval (CI) 11.1-17.9] versus 31.9% [95% CI 27.3-36.9] with doublet chemotherapy. Pooled median PFS was 2.69 and 4.05 months, respectively. The pooled median OS was 6.98 and 8.50 months, respectively. Multivariably, the odds ratio for ORR and the pooled median difference of PFS were statistically significant (P < 0.001 and P = 0.002) whereas the median difference in OS was not (P = 0.284). When including single-agent vinflunine or taxanes only, differences were significant only for ORR (P < 0.001) favoring doublet chemotherapy. No statistically significant differences in grade 3-4 toxicity were seen between the two groups.
Despite significant improvements in ORR and PFS, doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC. Prospective trials are necessary to elucidate the role of combination chemotherapy, with or without targeted agents, in the salvage setting. Currently, improvements in this field should be pursued considering single-agent chemotherapy as the foundation for new more active combinations.
在晚期尿路上皮癌（UC）的二线治疗中，化疗药物联合治疗与单药化疗相比的疗效和安全性尚不清楚。我们旨在研究与单药化疗相比，二线化疗中联合化疗对晚期 UC 的生存影响。
对包括铂类化疗后二线单药或联合化疗的研究进行文献检索。根据治疗臂，使用随机效应模型汇总试验水平数据，包括中位无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）概率和 3-4 级毒性。进行单变量和多变量分析，包括敏感性分析，调整 ECOG 表现状态≥1 和肝转移患者的比例。
选择了 46 个试验臂，共包括 1910 例患者：22 个单药组（n = 1202）和 24 个联合组（n = 708）。单药组的 ORR 为 14.2%（95%置信区间 [CI]：11.1-17.9），联合组为 31.9%（95%CI：27.3-36.9）。单药组的中位 PFS 分别为 2.69 和 4.05 个月，中位 OS 分别为 6.98 和 8.50 个月。多变量分析显示，ORR 的优势比和 PFS 的中位差异具有统计学意义（P < 0.001 和 P = 0.002），而 OS 的中位差异无统计学意义（P = 0.284）。当仅包括单药 vinflunine 或紫杉烷时，联合组的 ORR 差异有统计学意义（P < 0.001），有利于联合化疗。两组间 3-4 级毒性无统计学差异。
尽管 ORR 和 PFS 有显著改善，但与单药化疗相比，二线化疗中联合方案并未延长 UC 的 OS。需要进行前瞻性试验来阐明联合化疗（联合或不联合靶向药物）在挽救治疗中的作用。目前，应考虑以单药化疗为基础，开展新的更有效的联合化疗，以推进该领域的进展。
