Article

Cabozantinib shows intriguing activity in heavily pretreated urothelial carcinoma

Cabozantinib's single-agent activity opens the potential for combination approaches with immunotherapy in patients with heavily pretreated urothelial carcinoma.

Andrea B. Apolo, MD

Cabozantinib (Cabometyx) showed clinical activity in patients with heavily pretreated, platinum-refractory metastatic urothelial carcinoma, opening the potential to explore the multikinase inhibitor in combination regimens in this setting, according to findings from a phase 2 trial published in the Lancet Oncology.

In a cohort of patients with metastatic urothelial carcinoma, cabozantinib induced an objective response rate of 19% (95% CI, 9-34). Eight of 42 evaluable patients had responses, including 1 complete response and 7 partial responses.

“Cabozantinib has innate and adaptive immunomodulatory properties providing a rationale for combining cabozantinib with immunotherapeutic strategies,” lead study author Andrea B. Apolo, MD, medical oncologist and chief of the bladder cancer section of the Genitourinary Malignancies Branch, National Cancer Institute, and coinvestigators wrote.

There were 3 cohorts in the study: patients with metastatic urothelial carcinoma (cohort 1; n = 49), patients with bone only urothelial carcinoma metastases (cohort 2; n = 6), and patients with rare histologies of the genitourinary tract (cohort 3; n = 13). The 68 patients on the trial were enrolled between September 28, 2012, and October 20, 2015.

All patients were treated with cabozantinib at 60 mg orally once daily in 28-day cycles. Treatment was administered until disease progression or unacceptable toxicity. All trial participants were treated with at least 1 dose of cabozantinib.

Among the 57 evaluable patients across the entire study, the median follow-up time was 61.2 months (IQR, 53.8-70). Beyond the 8 responders in cohort 1, an additional 19 (45%) patients had stable disease, leading to an overall clinical benefit rate of 64% (95% CI, 48-79). The other 15 evaluable patients in cohort 1 had progressive disease.

Also in cohort 1, the median progression-free survival (PFS) was 3.7 months, the 6-month PFS rate was 37%, and the 12-month PFS rate was 10%. The median overall survival (OS) was 8.1 months, the 6-month OS rate was 64%, and the 12-month OS rate was 26%.

Three of the 5 evaluable patients in cohort 2 had a bone response per Na ¹⁸F-FDG PET/CT. In cohort 3, 5 of 10 evaluable patients with rare histologies achieved a best response of stable disease. The remainder of the evaluable patients in cohorts 2 and 3 had progressive disease.

The median PFS in cohort 2 was 5.3 months, the median OS was 9.3 months, and the 6-month OS rate was 80%. Among the patients in cohort 3, the median PFS was 2.9 months and the median OS was 5.8 months. The 6-month PFS and OS rates were 10% and 50%, respectively.

Regarding safety, the most frequently observed grade 3/4 adverse events across the study population were fatigue (n = 6), hypertension (n = 5), proteinuria (n = 4), and hypophosphatemia (n = 4). No death related to study treatment occurred.

“The clinical activity observed in this study provides a basis for further clinical investigations of cabozantinib for the treatment of metastatic urothelial carcinoma and other patient populations with rare genitourinary malignancies. Ongoing studies combining cabozantinib with immune-checkpoint inhibitors might lead to new therapeutic options for patients with advanced urothelial carcinoma and rare genitourinary malignancies,” wrote Apolo et al.

Some of the regimens being explored in these ongoing studies include cabozantinib plus nivolumab (Opdivo) with or without ipilimumab (Yervoy; NCT02496208); cabozantinib plus durvalumab (Imfinzi; NCT03824691); and cabozantinib plus atezolizumab (Tecentriq; NCT03170960).

In the genitourinary cancer treatment paradigm, cabozantinib is currently approved by the FDA as a monotherapy for the treatment of patients with advanced renal cell carcinoma.

Reference

Apolo AB, Nadal R, Tomita Y, et al. Cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma: an open-label, single-centre, phase 2 trial [published online July 6, 2020]. Lancet Oncol. https://doi.org/10.1016/ S1470-2045(20)30202-3

Related Videos
Interpreting ART toxicity and tolerability for bladder cancer, with Vedang Murthy, MD
Trinity Bivalacqua, MD, PhD, and Mark Tyson, MD, MPH, experts on bladder cancer
Trinity Bivalacqua, MD, PhD, and Mark Tyson, MD, MPH, experts on bladder cancer
Trinity Bivalacqua, MD, PhD, and Mark Tyson, MD, MPH, experts on bladder cancer
Trinity Bivalacqua, MD, PhD, and Mark Tyson, MD, MPH, experts on bladder cancer
Related Content
© 2024 MJH Life Sciences

All rights reserved.