In the UK phase II NEOBLADE trial reported in The Lancet Oncology, Hussain et al found that the addition of nintedanib to neoadjuvant gemcitabine/cisplatin did not improve pathologic complete response rate in patients with locally advanced muscle-invasive bladder cancer.
In the double-blind multicenter trial, 120 patients were randomly assigned between December 2014 and September 2018 to receive nintedanib at 150 mg or 200 mg twice daily for 12 weeks (n = 57) or placebo (n = 63) plus gemcitabine at 1,000 mg/m² on days 1 and 8 and cisplatin at 70 mg/m² on day 1 every 3 weeks. The primary endpoint was pathologic complete response at cystectomy or at day 8 of cycle 3 (plus or minus 7 days) if cystectomy was not performed in the intention-to-treat population.
Pathologic Complete Response Rates
Radical curative treatment was received by 49 (86%) of 57 patients in the nintedanib group (26 had cystectomy and 23 opted for organ preservation) and 53 (84%) of 63 patients in the control group (36 had cystectomy and 17 opted for organ preservation).
Pathologic complete response was achieved in 21 (37%) of 57 patients in the nintedanib group and 20 (32%) of 63 in the control group (odds ratio [OR] = 1.25, 70% confidence interval [CI] = 0.84–1.87, P = .28). Among 86 patients with available tissue for assessment of response at cystectomy or cystoscopy, pathologic complete response was achieved in 21 (51%) of 41 in the nintedanib group vs 20 (44%) of 45 in the control group (OR = 1.31, 70% CI = 0.84–2.06, P = .74).
Median follow-up was 33.5 months (interquartile range = 14.0–44.0 months). Median progression-free survival was not reached (95% CI = not reached to not reached) vs not reached (95% CI = 17 months to not reached) in the control group (hazard ratio = 0.53, 95% CI = 0.27-1.03, P = .058). Post hoc landmark analysis indicated rates of 82% vs 71% at 12 months, 79% vs 57% at 24 months, and 68% vs 52% at 60 months.
Adverse Events
Grade ≥ 3 adverse events occurred in 93% of the nintedanib group vs 79% of the control group (OR = 1.65, 95% CI = 0.74–3.65, P = .24). The most common in the nintedanib group were decreased neutrophil count (39% vs 11%, P = .0006), thromboembolic events (30% vs 21%, P = .29), and hypertension (16% vs 6%, P = .14). A total of 45 treatment-related serious adverse events occurred in the nintedanib group vs 43 in the control group. One patient in the control group died from an adverse event (myocardial infarction).
The investigators concluded: “The addition of nintedanib to chemotherapy was safe but did not improve the rate of [pathologic complete response] in muscle-invasive bladder cancer.”
Syed A. Hussain, MD, Department of Oncology and Metabolism, Academic Unit of Oncology, University of Sheffield, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Boehringer Ingelheim. For full disclosures of the study authors, visit www.thelancet.com.
