Since the first report by Morales and colleagues in
1976, the intravesical instillation of BCG has become
the mainstay of adjuvant treatment for non-muscle
invasive bladder cancers after endoscopic resection.
of 821 patients, which showed that median overall
survival was significantly longer with nivolumab
compared with everolimus (hazard ratio 0.73, p = 0.002).
In addition, the objective response rate for nivolumab
was 21. 5 percent versus 3. 9 percent for everolimus. The
benefit of nivolumab was consistent across prognostic
factors, including risk group, age, and number/sites
of metastases. In addition, the survival benefit was
not dependent on the expression of PD-L1 on tumor
cells. Thus, nivolumab is now one of the preferred
(category 1) options in second-line therapy for mRCC.
Additional studies are under way to examine the role
of other checkpoint inhibitors, such as pembrolizumab
and atezolizumab, both alone and in combination with
agents, such as interferon, pazopanib, and bevacizumab.
In addition to efficacy, side effects and tolerability need
to be carefully considered, as illustrated by data recently
presented regarding significant hepatotoxicity and more
than 80 percent grade 3/4 adverse events in patients with
RCC receiving both pazopanib and pembrolizumab.
Urothelial carcinoma of the bladder
Perhaps the greatest strides have been made in the
treatment of advanced bladder cancer, where the mainstay
had been cisplatinum-based combination chemotherapy.
The absence of promising agents, combined with the
challenges of completing clinical trials in this space, had
led to little progress over three decades. However, the FDA
has approved five immunotherapy drugs in the last year.
Atezolizumab targets and binds to PD-L1 and
demonstrated a 15 percent objective response rate. The
median duration of response was not reached with median
follow-up of 11. 7 months in the phase II IMvigor 210 trial,
which included patients with advanced or metastatic
bladder cancer with progression after previous platinum-based chemotherapy.
11 A second platinum-ineligible
cohort within the study also showed encouraging results,
with a 23 percent objective response rate and median
overall survival of 15. 9 months.
12 These findings led to
1. Morales A, Eidinger D, Bruce AW. Intracavitary
Bacillus Calmette-Guerin in the treatment of
superficial bladder tumors. J Urol. 1976;116( 2):180-183.
2. Law TM, Motzer RJ, Mazumdar M, et al. Phase III
randomized trial of interleukin- 2 with or without
lymphokine-activated killer cells in the treatment of
patients with advanced renal cell carcinoma. Cancer.
3. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T
immunotherapy for castration-resistant prostate
cancer. N Engl J Med. 2010;363( 5):411-422.
4. Postow MA, Callahan MK, Wolchok JD. Immune
checkpoint blockade in cancer therapy. J Clin Oncol.
2015; 33( 17):1974-1982.
5. Kantoff PW, Schuetz TJ, Blumenstein BA, et al.
Overall survival analysis of a phase II randomized
controlled trial of a Poxviral-based PSA-targeted
immunotherapy in metastatic castration-resistant
prostate cancer. J Clin Oncol. 2010;28:1099-1105.
6. U. S. National Institutes of Health. A randomized,
double-blind, phase 3 efficacy trial of Prostvac-V/F
+/- GM-CSF in men with asymptomatic or minimally
symptomatic metastatic castrate-resistant prostate
cancer (prospect). Available at: clinicaltrials.gov/ct2/
show/NCT01322490. Accessed June 26, 2017.
7. Beer TM, Kwon ED, Drake CG, et al. Randomized,
double-blind, phase III trial of ipilimumab versus
placebo in asymptomatic or minimally symptomatic
patients with metastatic chemotherapy-naïve
castration-resistant prostate cancer. J Clin Oncol.
8. Kwon ED, Drake CG, Scher HI, et al. Ipilimumab
versus placebo after radiotherapy in patients with
metastatic castration-resistant prostate cancer
that had progressed after docetaxel chemotherapy
(CA184-043): A multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014; 15( 7):700-712.
9. Motzer RJ, Escudier B, McDermott DF, et al.
Nivolumab versus everolimus in advanced renal-cell
carcinoma. N Engl J Med. 2015;373( 19):1803-1813.
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