accelerated FDA approval for both first-line and second-line treatment in bladder cancer; however, preliminary
reports on the phase III IMvigor 211 trial data do not
support a significant improvement in overall survival in
the second-line setting, which was the primary endpoint.
The ongoing phase III IMvigor 130 trial seeks to confirm
the findings in the platinum-ineligible population.
Avelumab and durvalumab are both FDA approved
in patients with disease progression after prior
chemotherapy and demonstrated objective response
rates of 13 percent and 17 percent, respectively.
Durvalumab is being evaluated as first-line therapy
alone and in combination with tremelimumab in the
phase III Danube trial. Pembrolizumab is also approved
in this space based on results from KEYNOTE-045,
with improvement in overall survival from 7. 4 to 103
months (hazard ratio 0.73, p = 0.002).
15 The benefit was
independent of measurement of PD-L1 expression.
The anti-PD- 1 nivolumab was the second agent
approved by the FDA as a second-line agent after
a prior platinum-containing regimen. Check Mate
275 confirmed the findings from the phase 1/2 trial
(CheckMate 032), with an objective response in 20 percent
of patients and complete response rate of 2. 6 percent,
with mediation duration of response of 10. 3 months.
The efficacy of novel immunotherapeutics,
particularly checkpoint inhibitors, hold promise
for a wide variety of tumor types. The next critical
steps will be identifying the patients most likely to
benefit from therapy and to develop and validate
relevant biomarkers. In addition, these drugs will
likely be used in combination with many others to
optimize outcomes while minimizing side effects.
Open Alliance trials can be viewed at www.
10. American Society of Clinical Oncology. Meeting
abstracts. A phase I/II study to assess the safety and
efficacy of pazopanib (PAZ) and pembrolizumab
(PEM) in patients (pts) with advanced renal cell
carcinoma (aRCC). Available at: abstracts.asco.
org/199/ AbstView_199_180924.html. Accessed June
11. Rosenberg JE, Hoffman-Censitis J, Powles T, et al.
Atezolizumab in patients with locally advanced
and metastatic urothelial carcinoma who have
progressed following treatment with platinum-based
chemotherapy: A single-arm, multicenter, phase 2
trial. Lancet. 2016;387:1909-1920.
12. Balar AV, Galsky MD, Rosenberg JE, et al.
Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and
metastatic urothelial carcinoma: A single-arm,
multicenter, phase 2 trial. Lancet. 2017;389: 67-76.
13. Apolo AB, Infante JR, Balmanoukian A, et al.
Avelumab, an anti-programmed death-ligand 1
antibody, in patients with refractory metastatic
urothelial carcinoma: Results from a multicenter,
phase Ib study. J Clin Oncol. 2017; 35( 19):2117-2124.
14. Massard C, Gordon MS, Sharma S, et al. Safety
and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand- 1 immune checkpoint
inhibitor, in patients with advanced urothelial bladder
cancer. J Clin Oncol. 2016; 34( 26):3119-3125.
15. Bellmunt J, de Wit R, Vaughn DJ, et al.
Pembrolizumab as a second-line therapy
for advanced urothelial carcinoma.
N Engl J Med. 2017;376( 11):1015-1026.
16. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab
in metastatic urothelial carcinoma after platinum
therapy (Check Mate 275): A multicentre, single-arm,
phase 2 trial. Lancet Oncol. 2017; 18( 3):312-322.
The efficacy of novel immunotherapeutics, particularly checkpoint
inhibitors, hold promise for a wide variety of tumor types.