Clinical Pearls & Morning Reports
Combination platinum-based chemotherapy is the standard of care for first-line treatment of advanced urothelial carcinoma in patients who are suitable candidates for platinum-based therapy. Powles et al. evaluated avelumab as maintenance therapy in patients who had received first-line platinum-based chemotherapy for advanced urothelial carcinoma. Read the NEJM Original Article here.
Q: How effective is first-line chemotherapy for advanced urothelial carcinoma?
A: Although chemotherapy is active (objective response in 40 to 50% of patients; disease control in 75 to 80%), most patients have disease progression within approximately 9 months, and the median overall survival is 14 to 15 months with cisplatin-based regimens and 9 to 10 months with carboplatin-based regimens among patients who are not suitable candidates for cisplatin-based therapy.
Q: What are some of the characteristics of urothelial carcinoma?
A: Urothelial carcinoma is characterized by genomic instability, high programmed cell death ligand 1 (PD-L1) protein expression, DNA damage-response mutations, and a high tumor mutational burden, which are features associated with an increased response to immune checkpoint inhibitors in several cancer types. Avelumab is an anti-PD-L1 antibody that has been approved in several countries for the treatment of locally advanced or metastatic urothelial carcinoma after disease progression during or after platinum-containing chemotherapy.
A: This phase 3 trial showed that patients with advanced urothelial carcinoma who had disease that had not progressed with first-line platinum-based chemotherapy had significantly longer overall survival with maintenance avelumab therapy than with supportive care alone; this finding applied to both the overall population and the PD-L1–positive population. Patients in the avelumab group also had longer progression-free survival than patients in the control group. The authors note that the efficacy seen in the avelumab group may be due in part to maintenance treatment being administered only to patients with disease control; therefore, patients with rapidly progressive disease during first-line chemotherapy, which might be refractory to immunotherapy, were not included. Further studies to characterize patients with rapidly progressive (primary resistant) disease will be useful.
A: Among the avelumab-treated patients, 101 (29.4%) had an adverse event that was categorized as being immune-related according to a prespecified case definition, including 24 patients (7.0%) with a grade 3 event. No grade 4 or fatal immune-related adverse events occurred. The most frequent category of immune-related adverse events was thyroid disorders, which occurred in 42 patients (12.2%).