Immunotherapy Efficacy in Patients with Metastatic Bladder Cancer
In the past several years, many checkpoint inhibitors have been approved by the FDA for use in treating patients with metastatic bladder cancer. These drugs offer new options for doctors who are treating these patients, but they also pose the challenge of determining the best order in which to use them. Joaquim Bellmunt, MD, Ph.D., director of the Bladder Cancer Center at Dana-Farber Cancer Institute, recently discussed these developments in the treatment of bladder cancer and advised the medical community on how best to use the drugs.
Bellmunt suggests that clinicians refer to two important clinical trials when seeking data on the efficacy of immunotherapy in patients with metastatic bladder cancer.
The first trial, KEYNOTE-045, revealed that patients who received the drug pembrolizumab (Keytruda) showed long-term improvements in comparison to patients who received chemotherapy as a frontline treatment.
The trial’s initial data allowed the FDA to approve pembrolizumab back in May 2017 as the first line of treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC). These patients should also not be candidates for cisplatin-containing chemotherapy. Pembrolizumab is also recommended for patients with locally advanced or mUC who experienced a progression of their disease either during or after receiving chemotherapy containing platinum.
Results of this trial revealed that patients responded well to the PD-L1 inhibitor atezolizumab (Tecentriq). The FDA subsequently approved the drug as a frontline treatment for patients with locally advanced or mUC who experienced a progression of their disease during or after chemotherapy containing platinum.
One of the complications that clinicians face when using these drugs has to do with safety issues. In May of 2018, the FDA warned against using single-agent immune checkpoint inhibitors as frontline treatments for patients who are considered “biomarker-negative.” The European Medicines Agency also put forth a similar warning. Both agencies based their warnings on data that showed a lower overall survival rate with pembrolizumab and atezolizumab as opposed to platinum-based chemotherapy in biomarker-negative patients.
Although there have not been any official comparisons, Bellmunt advises the medical community that pembrolizumab be the first line of treatment for patients with metastatic bladder cancer, followed by atezolizumab.
As Bellmunt explains, in just the past year, the FDA has approved 7 immunotherapy agents that have potential efficacy. Of those 7, 5 were approved for second-line treatment in patients who have seen disease progress during or after platinum-based chemotherapy. The other two were approved as frontline treatment for patients who are not candidates for chemotherapy.