New study, involving eight Italian research centres, concluded that an aligned approach to the treatment of advanced bladder cancer is much needed, while confirming previously published results on survival estimates of associated salvage therapies.
According to the lead author, Dr. Francesco Atzori, progress in developing new effective drugs in bladder cancer has been stagnant in the last decades.
"In patients who recur or who are refractory to first-line therapy, response rates and outcomes are grim, and to date, no second-line therapy has been clearly established," he explained.
The authors state that while upfront chemotherapy (CT) confers over 50% response rate, progression free survival and overall survival rates are still dismal. While vinflunine is approved by the EMA for progressive bladder cancer after platinum-based therapy, the US FDA has no approved agents.
In the course of the study, the researchers retrospectively queried all patients receiving 2nd and 3rd line regimens in Italy in the period between 2001 and 2013. The inclusion criteria included failure of one or two prior CT regimens for metastatic disease and no exclusion of specific salvage regiments, including targeted agents. Distribution of treatments and outcome parameters were the primary endpoints.
The authors identified a total of 160 eligible pts across 8 centers nationwide. Median age was 67 years (IQR 39-82), most frequent sites of disease at relapse were: nodes 71% (nodes only 43, 26.9%); lung 30%, bone 26% and liver 20%. Bellmunt Score available in 147 out of 160 patients was 0, 1, 2 and 3 in 63 (43%), 59 (40%), 20 (14%) and 5 (3%) patients respectively.
Regiments used as upfront CT were cisplatin-gemcitabine in 65 patients (41%), carboplatin-G in 50 patients (31%), MVAC in 25 patients (16%), other combination CT in 5 patients (3%) and single-agent CT in 15 patients (9%).
In 2nd line 42 patients (26%) received paclitaxel, 40 (25%) vinflunine, 21 (13%) pazopanib, 10 (6%) MVAC, 47 (29%) other drugs alone or combined.
75 out of 160 patients (47%) received a 3rd line regimen: 19 (25%) paclitaxel, 15 (20%) pazopanib, 11 (15%) MVAC, 30 patients (40%) miscellaneous. Median time-to-relapse to 1st line was 2 months. Overall response rate in 2nd line was 21% (32 out of 160 patients) and 21% in 3rd line (16 out of 75 patients); median progression-free survival was 2,8 and 2 months in 2nd and 3rd line respectively, median overall survival was 16 months and 20 months, in 2nd and 3rd lines respectively. Patients treated with paclitaxel and vinflunine in 2nd line showed a median progression free survival of 2.7 and 3.3 months while overall survival was 13.5 and 13.4 months respectively.