March 21, 2017
2 min read

Nivolumab safe, beneficial for urothelial carcinoma

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Nivolumab demonstrated clinical benefit and an acceptable safety profile in patients with metastatic or surgically urothelial carcinoma who were previously treated, according to data from a phase 2 trial.

“Nivolumab is a fully human IgG4 PD-1 inhibitor antibody that selectively blocks interaction between PD-1 expressed on activated T cells and PD-L1 and PD-L2 expressed on tumor cells, restoring T-cell-driven anti-tumor response by disrupting PD-L1-mediated signaling,” Padmanee Sharma, MD, professor of the departments of genitourinary medical oncology and immunology at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “Nivolumab has shown antitumor activity and improved OS across several tumor types, and has an acceptable safety profile.”

Sharma and colleagues performed a multicenter, single-arm phase 2 study on adults (n = 270) with metastatic or surgically unresectable locally advanced urothelial carcinoma at 63 sites in 11 countries between March 9, 2015, and Oct. 16, 2015. Patients received intravenous nivolumab 3 mg/kg every two weeks until disease progression and clinical deterioration, unacceptable toxicity or other “protocol-defined reasons.”

Overall objective response served as the primary endpoint.

Median follow-up was 7 months (IQR, 2.96-8.77). Fifty-two patients achieved confirmed objective response (19.6%; 95% CI, 15-24.9). Twenty-three of 81 patients with PD-L1 expression of 5% or greater achieved a confirmed objective response (28.4%; 95% CI, 18.9-39.5), as did 29 of 122 patients with PD-L1 expression of 1% or greater (23.8%; 95% CI, 16.5-32.3), and 23 of 143 patients (16.1%, 95% CI, 10.5-23.1) with PD-L1 expression of less than 1%.

Forty-eight (18%) of 270 patients experienced grade 3 or grade 4 adverse events, the most common of which were fatigue and diarrhea (n = 5 for both). Researchers attributed three deaths — of pneumonitis, acute respiratory care and cardiovascular failure — to treatment.

Researchers acknowledged that the study was limited by its single-arm nature.

“Our phase 2 study provides data with similarities to those from IMvigor 210, which showed clinical activity for an antibody against PD-L1 in patients with metastatic urothelial carcinoma,” Sharma and colleagues wrote. “However, although these findings are clinically meaningful, many patients in this setting did not benefit from either nivolumab or atezolizumab, suggesting that further research is needed. In view of the scarcity of treatment options and high unmet medical need in this patient population, these data support the use of nivolumab as a new treatment option if platinum-based chemotherapy is unsuccessful.” – by Andy Polhamus

Disclosure: Sharma reports fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Constellation and GlaxoSmithKline, owns a patent with Jounce and holds stock options with Evelo, Jounce and Kite Pharma. Please see the full study for a list of all other researchers’ relevant financial disclosures.