Atezolizumab in platinum-ineligible urothelial cancer patients - Beyond the Abstract

The standard of care for patients with advanced muscle-invasive urothelial carcinoma is cisplatin-based chemotherapy. However up to two-thirds of patients are “unfit” to receive cisplatin-based chemotherapy due to impaired renal function, poor performance status, hearing loss, neuropathy or heart failure. A recent study published in The Lancet tested immune-checkpoint inhibition as a therapeutic strategy for this group of patients.

The investigators conducted a large multicenter phase 2 study of the anti-PDL-1 immune checkpoint inhibitor atezolizumab in a cisplatin-unfit cohort of patients with locally advanced or metastatic UC. The study demonstrated an overall response rate of 23% and a complete response rate of 9%. Interestingly, 70% of responses that were still ongoing. The reported median overall survival (OS) was 15.9 months. The study examined factors that predict response to Atezolizumab and identified a higher response rate associating with larger tumor mutational burdens. Interestingly, the study showed 39% response rate in patients with upper tract urothelial carcinoma (UTUC), this finding is interesting but requires confirmation in additional studies. This important study shows promising efficacy, especially when considered with recently presented data using a different immune-checkpoint inhibitor Pembrolizumab in the same patient population of platinum-ineligible patients.

Several studies using immune-checkpoint inhibition are planned or ongoing in the treatment of patients with different stages of urothelial carcinoma spanning the entire spectrum of the disease. The results of these studies are expected to result in newer therapeutic advances for urothelial cancer patients in the near future.

Written by: Bishoy M. Faltas, MD

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Balar AV, Galsky MD, Rosenberg JE, et al, for the IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, two-cohort, phase 2 trial. Lancet 2016; Dec 7. http://dx.doi. org/10.1016/S0140-6736(16)32455-2

Faltas BM, Tagawa ST. Immune-checkpoint blockade in cisplatin-ineligible patients with urothelial cancer Lancet 2016; Dec 7.

Balar A, Bellmunt J, O’Donnell PH, et al. Pembrolizumab (pembro) as first- line therapy for advanced/unresectable or metastatic urothelial cancer: preliminary results from the phase 2 KEYNOTE-052 study. Ann Oncol 2016; 27 (suppl 6).