medwireNews: Results from the phase 2 NEOBLADE trial show no significant improvement in the rate of pathologic complete response among patients with locally advanced muscle-invasive bladder cancer (MIBC) who receive the multikinase inhibitor nintedanib alongside standard neoadjuvant chemotherapy.
The study included 120 patients with locally advanced MIBC (stage T2–T4, N0, M0) who were randomly assigned to receive either oral nintedanib 150 or 200 mg twice a day for 12 weeks (n=57) or placebo (n=63) alongside four 3-weekly cycles of gemcitabine and cisplatin chemotherapy.
There was no significant difference in pathologic complete response rates among those who did and did not receive nintedanib, at 37% versus 32%, as assessed at radical cystectomy and lymphadenectomy or on day 8 of cycle 3 for patients who instead received bladder-preserving treatment, consisting of radiotherapy with or without chemotherapy.
The post-hoc progression-free survival rate at 12 months was 82% for nintedanib-treated patients and 71% for controls, and the median duration was unreached in both arms, giving a hazard ratio (HR) of 0.53 that did not reach statistical significance.
The investigators add that in a post-hoc analysis of overall survival after a median follow-up of 33.5 months, the median durations significantly favored chemotherapy with rather than without nintedanib, at 50.6 months and not reached, respectively, and a HR of 0.45.
“The overall survival benefit seen in a post-hoc analysis in this study did not seem to be driven by the patients’ choice of curative treatment modality,” note Syed Hussain (University of Sheffield, UK) and colleagues.
They report that among nintedanib-treated patients, 26 chose cystectomy and 23 organ preservation, with a curative modality in 49 of the 57 patients. By contrast, in the control arm 36 patients underwent cystectomy and 17 organ preservation, with a curative modality in 53 of 63 patients.
“These data suggest that improvements in the post-hoc endpoint of overall survival might have been driven by nintedanib rather than by the choice of radical treatment,” the researchers comment.
But they emphasize that “the study was not powered for this analysis, and this result should therefore be interpreted with caution.”
The study also showed that “intensification of neoadjuvant chemotherapy with the addition of multikinase inhibitors can be safely delivered,” say Hussain et al.
Grade 3 or worse toxicities were observed in 93% and 79% of patients in the nintedanib and control groups, respectively, a nonsignificant difference. The most common grade 3 or more severe events were decreased neutrophil count (39 vs 11% of patients in nintedanib and control arms, respectively) and thromboembolic events (30 vs 21%).
There were significantly more gemcitabine dose reductions in those who received nintedanib compared with those who did not, at corresponding rates of 31% and 16%, but the proportion of patients requiring cisplatin dose reductions was comparable between the two groups.
Overall, these findings “could merit further investigation in the neoadjuvant setting” but at present, “cisplatin-based neoadjuvant chemotherapy remains the standard of care for the treatment of muscle-invasive bladder cancer,” write the NEOBLADE researchers in The Lancet Oncology.
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