ORLANDO – Two checkpoint inhibitors have been added to the advanced bladder cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN).
Nivolumab (Opdivo) and atezolizumab (Tecentriq) are now listed as second-line therapies in patients with locally advanced or metastatic cancer, said of Fox Chase Cancer Center in Philadelphia, at the .
However, the agents were given a category 2A designation, meaning that there was substantial concurrence by an NCCN committee on their inclusion, but evidence from randomized phase III clinical trials was still lacking.
Nonetheless, results from phase II trials still came out in favor of the two checkpoint inhibitors, specifically and .
"Overall, PD-1 checkpoint inhibitors perform similarly in the post-platinum setting," Plimack stated.
Checkmate 275 is a single-arm study in adult patients with metastatic or surgically unresectable locally advanced urothelial carcinoma who received nivolumab 3 mg/kg intravenously every 2 weeks until disease progression and clinical deterioration, unacceptable toxicity, or other protocol-defined reason. In 265 patients, the median follow-up for overall survival (OS) was 7 months (IQR 2.96-8.77), and the confirmed objective response was achieved in 19.6% (95% CI 15.0-24.9) of 265 patients.
In the trial, called IMvigor210, 119 patients with previously untreated locally advanced or metastatic urothelial cancer, who were cisplatin ineligible, received one or more doses of atezolizumab. At 17.2 months' median follow-up, the objective response rate was 23% (95% CI 16-31), the complete response rate was 9% (n=11), and 19 of 27 responses were ongoing. Median response duration was not reached as of study publication in January 2017.
The guidelines also list paclitaxel (Taxol) or docetaxel (Taxotere), gemcitabine (Gemzar), and pemetrexed (Alimta) as possible second-line options in this patient population.
In addition, in selected patients, other possible treatments after progression on first line platinum-based chemotherapy are:
- Nab-paclitaxel (Abraxane)
- Ifosfamide (Ifex)
- Methotrexate
- Dose-dense methotrexate
- Ifosfamide, doxorubicin, and gemcitabine (Gemzar)
- Gemcitabine and nab-paclitaxel
- Gemcitabine and cisplatin
- Vinblastine doxorubicin, and cisplatin
Plimack said that pembrolizumab (Keytruda) may be a future addition to the NCCN guidelines, based on findings from the phase III study, in which 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy received pembrolizumab at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine.
The median OS in the total population was 10.3 months (95% CI 8.0-11.8) in the pembrolizumab group versus 7.4 months (95% CI 6.1-8.3) in the chemotherapy group, for a hazard ratio for death of 0.73 (95% CI 0.59-0.91, P=0.002). The median OS among patients who had a tumor PD-L1 combined positive score of 10% or more was 8 months (95% CI 5.0-12.3) in the pembrolizumab group versus 5.2 months (95% CI 4.0-7.4) in the chemotherapy group (HR 0.57, 95% CI 0.37-0.88; P=0.005).
Plimack noted that stratifying patients by PD-L-1 status didn't seem to make a big impact on outcomes, and it may be that the level of PD-L-1 is not a good biomarker for treatment success.
Other possible candidates on the horizon are and , she said.
Disclosures
Plimack disclosed relevant relationships with Acceleron, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Exelixis, Genentech, Merck, Novartis, Peloton Therapeutics, Pfizer, and Roche Laboratories.
Primary Source
National Comprehensive Cancer Network
Plimack E "Updates to the management of advanced bladder cancer" NCCN 2017.