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.
Researchers aimed to study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced urothelial carcinoma.
Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after Platinum-based chemotherapy.
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 objective response rate ( 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 progression-free survival ( PFS ) was 2.69 and 4.05 months, respectively.
The pooled median overall survival ( 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 less than 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 less than 0.001 ) favoring doublet chemotherapy.
No statistically significant differences in grade 3-4 toxicity were seen between the two groups.
In conclusion, despite significant improvements in ORR and PFS, doublet regimens did not extend overall survival compared with single agents for the second-line chemotherapy of urothelial carcinoma.
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. ( Xagena )
Raggi D et al, Ann Oncol 2016;27:49-61