Cabozantinib used in a switch maintenance setting did not benefit patients with metastatic urothelial carcinoma who had previously derived benefit from platinum-based chemotherapy, according to final results from the ATLANTIS study presented at the 2022 ASCO Annual Meeting (Abstract LBA4505).
Robert J. Jones, MA, PhD, MBChB, of the University of Glasgow, United Kingdom, and colleagues hypothesized that switch maintenance therapy with the TKI cabozantinib in these patients would improve outcomes for metastatic disease.
The phase-2 ATLANTIS study was designed to test multiple maintenance therapies in patients with metastatic urothelial carcinoma who had completed four to eight cycles of platinum-based chemotherapy without disease progression. Patients who were not selected for other maintenance therapies based on predictive biomarkers were randomly assigned to start either cabozantinib 40 mg once-daily or matching placebo within 10 weeks of completing chemotherapy.
The primary endpoint was progression-free survival. To meet the required hazard ratio (HR) of 0.67, 114 events in 140 patients were required. This was later modified to 50 events in 57 patients after a change in standard of care occurred (maintenance avelumab).
Median progression-free survival was 13.7 weeks for patients assigned to cabozantinib compared with 15.8 weeks in patients assigned to placebo (adjusted HR=0.89 favoring cabozantinib, 80% CI, 0.61-1.3).
No difference in overall survival was observed (HR=0.80; 80% CI, 0.52-1.23).
The researchers noted that cabozantinib was tolerable. Median duration of treatment was 13 28-day cycles with cabozantinib and 10 28-day cycles with placebo. However, about 43% of patients required dose reduction in the cabozantinib arm compared with 9.7% of patients in the placebo arm.
The most common adverse events of any grade were more common with cabozantinib and included fatigue (56.7% vs. 32.2%; P=.02), hypertension (43.3% vs. 12.9%; P=.01), nausea (30% vs. 19.4%; P=.36), and diarrhea (40.0% vs. 6.5%; P<.01).