Cabozantinib fails as first-line maintenance therapy in urothelial cancer

The phase 2 ATLANTIS study did not demonstrate a clinical benefit of cabozantinib over placebo as maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial cancer. Moreover, placebo is no longer an acceptable control arm for patients with this condition.

Until January of last year, platinum-based chemotherapy followed by surveillance was the standard first-line treatment for patients with advanced urothelial cancer. In the current phase 2 ATLANTIS screening trial (ISRCTN25859465), Prof. Robert Jones (University of Glasgow, UK) and colleagues evaluated whether patients with advanced urothelial cancer who are ineligible for inclusion in precision-medicine arms of maintenance therapy trials respond to cabozantinib [1]. Patients with advanced urothelial cancer received 4–8 cycles of first-line chemotherapy and were subsequently randomised 1:1 to cabozantinib (40 mg, oral, once daily) or placebo if they tested negative for all biomarkers. Recruitment of patients was stopped early, because research in the meantime demonstrated that avelumab may become the standard-of-care in the maintenance setting of patients with this indication [2]. Therefore, it was unethical to randomise patients to the placebo arm, leaving the total number of randomised patients to 61. Progression-free survival (PFS) was the primary outcome.

The median PFS was 13.7 months in the cabozantinib arm and 15.8 months in the placebo arm (HR 0.89; P=0.35), not reaching the primary endpoint. The median overall survival rates demonstrated similar results (cabozantinib 75.5 months vs placebo 82.9 months; HR 0.80; P=0.25). In terms of safety, anorexia, diarrhoea, fatigue, hypertension, hypothyroidism, rash, and neutropenia were more common in the cabozantinib arm. According to Prof. Jones, these were all known and manageable adverse events of this agent.

“This study does not support further investigation of cabozantinib as single agent maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial cancer,” concluded Prof. Jones.

1. Jones RJ, et al. A randomised, double blind, phase II clinical trial of maintenance cabozantinib following chemotherapy for metastatic urothelial carcinoma (mUC): Final analysis of the ATLANTIS cabozantinib comparison. LBA4505, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.
2. Powles T, et al. N Engl J Med. 2020;383(13):1218–1230.

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Posted on 5 August 202217 May 2024