More than a year has passed since Tecentriq (atezolizumab), new immunotherapy for bladder cancer in 30 years, received insurance benefit as a second-line treatment. However, deciding whether to prescribe Tecentriq based on the patient’s programmed death-ligand 1 (PD-L1) expression seemed ineffective, an oncologist said.
Kim In-ho, a professor at the Oncology Department of Seoul St. Mary’s Hospital, recently met with Korea Biomedical Review to explain how Tecentriq was being used.
“In the bladder cancer treatment, there was no other option other than platinum-based chemotherapy. If the standard first-line treatment fails, paclitaxel could be tried in the second therapy, but its effect was nearly zero, and the response rate was below 10 percent,” Kim said. Under such circumstances, a novel drug called Tecentriq arrived in the market in 30 years, he added.
The Ministry of Food and Drug Safety has approved Tecentriq as the first-line treatment of patients with locally advanced or metastatic bladder cancer with PD-L1 expression at 5 percent or more. The drug is also reimbursable as the second-line treatment for patients who failed platinum-based chemotherapy and whose PD-L1 expression is over 5 percent.
However, the biomarker PD-L1 does not work well to gauge Tecentriq’s therapeutic effect, Kim said.
“Tecentriq showed differences in therapeutic effects depending on PD-L1 expression in a phase-2 trial. In a phase-3 study, however, there was no significant difference. So, PD-L1 expression is a poor biomarker to prescribe the immunotherapy,” Kim noted.
Tecentriq’s insurance benefit is available when a patient’s PD-L1 expression is more than 5 percent in the second-line treatment, but only 20-25 percent of patients show positive PD-L1 expression, Kim said. “Thus, only 20-25 percent of patients can get the insurance benefit using Tecentriq,” he added.
Asked if there is any biomarker other than PD-L1 that can measure the efficacy of Tecentriq, Kim answered “yes.”
“There are lots of research data, including phase-3 IMvigor211. In the study, patients with high tumor mutation burden (TMB) had a better effect of Tecentriq, and those who have both high TMB and PD-L1 expression had an even better therapeutic effect,” he said.
The medical community uses PD-L1 expression as a marker because TMB testing costs much more, according to the professor.
As bladder cancer occurs mostly in elderly patients, safety should be a significant factor in the treatment, Kim went on to say. “More patients should have access to immunotherapies which are safer and more tolerable than conventional therapies,” he emphasized.
Kim said eight out of 10 bladder cancer patients are in their 60s, and platinum-based chemotherapy is worrisome in safety and tolerability. “Tecentriq is a meaningful treatment option for patients who find it hard to tolerate the rigorous therapy,” he said.
Most immunotherapies have about 20 percent incidence of adverse reactions in Grade 3 or higher, which is only half of that of chemotherapies, Kim said. Most cases of the treatment discontinuation occur in chemotherapies, not immunotherapies, he added.
Kim noted he had a dramatically successful case using Tecentriq.
“Lungs after surgery of bladder cancer failed in platinum-based chemotherapy. After Tecentriq treatment, the patient is in the complete remission for about 10 months now,” Kim said. “If the patient maintains the current condition, it will be the most dramatic case to benefit from Tecentriq.”
He introduced another case where a patient, who was not apt for standard treatment, benefited from Tecentriq.
“Cancer in a patient who had kidney surgery had recurred. The patient is now receiving Tecentriq, and the response is excellent,” Kim said. “We might consider surgery, but as the patient has already removed a kidney, we are maintaining the current treatment due to the burden of dialysis.”