medwireNews: Cabozantinib has shown promising clinical activity and tolerability in patients with metastatic urothelial carcinoma who have progressed on platinum chemotherapy in a single-center phase 2 trial.
The study, published in The Lancet Oncology, comprised three cohorts that included metastatic urothelial cancer patients with measurable disease as per RECIST criteria (n=49) or bone-only metastases (n=6), as well as patients with rare genitourinary tract tumors (n=13). All participants received the multikinase inhibitor at a daily dose of 60 mg in 28-day cycles.
During a median follow-up of 61.2 months, treatment with cabozantinib led to an objective response rate (ORR) of 19% – consisting of one complete and seven partial responses – among the 42 evaluable patients with measurable disease. An additional 45% of patients achieved stable disease, giving a clinical benefit rate of 64%.
The researchers note that all but two of these participants subsequently died as a result of disease progression. But the patient who achieved complete response had an ongoing response at data cutoff, while another patient maintained stable disease for 8 months and then achieved a complete response with the addition of an immune checkpoint inhibitor.
Among the five evaluable patients with bone-only disease, 60% achieved a bone response as assessed by imaging, while 50% of the 10 evaluable participants in the rare histology tumor cohort had stable disease as the best response to cabozantinib and the remainder had progressive disease.
Median progression-free survival (PFS) was 3.7, 5.3, and 2.9 months for patients with measurable disease, bone-only disease, and rare histology tumors, respectively, and corresponding median overall survival (OS) times were 8.1, 9.3, and 5.8 months.
Andrea Apolo (National Cancer Institute, Bethesda, Maryland, USA) and team say that “cabozantinib’s safety profile and common adverse events were similar to those previously reported.”
The most common adverse events of grade 3–4 among participants across all three cohorts were fatigue (9%), hypertension (7%), hypophosphatemia (6%), and proteinuria (6%).
In all, 66% of the study participants required a dose reduction and 74% required a dose delay. Four patients discontinued cabozantinib due to a treatment-related adverse event of grade 3 – two cases of elevated aspartate aminotransferase and one each of proteinuria and decreased platelet count – while one patient discontinued due to a grade 1 transient ischemic attack not related to treatment.
Exploratory translational analyses highlighted the immunomodulatory properties of cabozantinib, such as its effect on the expression of PD-1 on regulatory T cells, leading the authors of an accompanying commentary to suggest that “the combination of cabozantinib with an immune checkpoint inhibitor might be a reasonable therapeutic strategy against metastatic urothelial carcinoma.”
Eiji Kikuchi and Nozomi Hayakawa, from the St Marianna University School of Medicine in Kawasaki, Japan, add that “[f]urther study is warranted to pursue the quality-of-life assessment and the extent of long-term adverse events in patients with metastatic urothelial cancer treated with cabozantinib.”
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Lancet Oncol 2020; doi:10.1016/S1470-2045(20)30202-3
Lancet Oncol 2020; doi:10.1016/S1470-2045(20)30236-9