Cabozantinib as a choice for platinum-refractory metastatic urothelial cancer
Mené sur 68 patients atteints d'un carcinome urothélial de stade métastatique et réfractaire aux sels de platine, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du cabazantinib (durée médiane de suivi : 61,2 mois)
Résumé en anglais
In the field of systemic therapy for metastatic urothelial cancer, more than 30 years has passed without the development of any definitive subsequent-line of therapy for patients who do not respond to platinum-based combination chemotherapy. However, immune checkpoint inhibitors, such as pembrolizumab, have built a solid evidence base for a role as a second-line therapy for patients with platinum-refractory metastatic urothelial cancer. The pivotal phase 3 trial, KEYNOTE-045, evaluating the survival benefit of pembrolizumab in 542 patients with platinum-refractory metastatic urothelial cancer, showed that median overall survival in the pembrolizumab group was 10·3 months (95% CI 8·0–11·8), which was significantly longer than that in paclitaxel, docetaxel, or vinflunine chemotherapy group (7·4 months [6·1–8·3]). Furthermore, new therapeutic drugs, such as antibody-drug conjugates and fibroblast growth factor receptor (FGFR) inhibitors, are being tested as a subsequent-line of systemic therapy for patients with platinum-refractory metastatic urothelial cancer in intensive clinical trials. One of the novel antibody-drug conjugates, enfortumab vedotin, is designed to deliver a microtubule-disrupting agent to cells that express nectin-4, which is highly expressed by urothelial cancer cells. In a phase 1, single-arm, escalation, and expansion study evaluating the safety and tolerability of enfortumab vedotin in 112 patients with metastatic urothelial cancer who had disease progression after platinum-based chemotherapy or anti-PD-L1 therapy, enfortumab vedotin showed an objective response rate of 42·9% (95% CI 33·6–52·6) and a median overall survival of 12·3 months (95% CI 9·3–15·3). One of the FGFR inhibitors, erdafitinib, shows antitumour activity in tumours with FGFR alterations, which is reported in 20–30% of metastatic urothelial cancer patients. In a phase 2 single-arm study evaluating the efficacy of erdafitinib in 99 patients with metastatic urothelial cancer who had disease progression during or after systemic chemotherapy, erdafitinib showed an objective response rate of 40% (95% CI 31–50) and a median overall survival of 13·8 months (95% CI 9·8–not reached).
