Immunotherapy administered before and after chemotherapy, along with surgical removal of the bladder, improved survival compared to chemotherapy alone in patients with muscle-invasive bladder cancer, according to results of a recent clinical trial that will be published Sept. 15 in the New England Journal of Medicine.
The findings highlight a new treatment regimen for patients with locally advanced bladder cancer that improves treatment response and survival with minimal side effects, said study co-author Dr. Joshua Meeks, a professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine who led the enrollment and clinical trial at Northwestern Medicine.
“This is the first trial that's shown that you can add immunotherapy to chemotherapy and show improved response and a survival benefit,” said Meeks, who also is a Northwestern Medicine physician and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This is very likely to become the new standard of care.”
Bladder cancer is one of the most common cancers worldwide, with an estimated 573,000 new cases and more than 200,000 deaths globally in 2020. Locally advanced bladder cancer, which is more common in older adults and men, has grown beyond the inner lining of the bladder and invaded nearby tissues but has not yet spread to distant organs (known as metastatic). One in three bladder cancers becomes advanced and will require radical treatment, including bladder removal.
For more than 20 years, the standard of care for advanced bladder cancer (stages II to III) involved chemotherapy followed by radical cystectomy (surgical removal of the bladder and surrounding lymph nodes). However, approximately half of patients experience recurrence within three years after treatment.
“These patients have the most to lose or gain, so that's why we treat them more aggressively,” Meeks said. “What hasn't been clear is if adding immunotherapy to chemotherapy has any benefit. In the metastatic setting, it has not been necessarily as successful.”
In the current clinical trial, more than 1,000 patients with localized bladder cancer at academic medical centers from 22 countries in Europe, Asia, North America, Australia and South America were enrolled.
Participants were randomized to receive durvalumab immunotherapy plus chemotherapy (gemcitabine and cisplatin) every three weeks for four cycles; then radical cystectomy followed by durvalumab every four weeks for eight cycles (combination-treatment group); or neoadjuvant chemotherapy followed by radical cystectomy alone (control group).
After 24 months, follow-up analyses showed that event-free survival (patients did not experience a relapse, progression of disease or death during the time measured) and overall survival (length of time from start of treatment or diagnosis until patient dies from any cause) was longer in the combination-treatment group compared to patients in the control group who received chemotherapy with radical cystectomy alone.
In the experimental group, event-free survival was 67.8% and overall survival was 82.2%. In the chemotherapy with radical cystectomy group, event-free survival was 59.8% and overall survival was 75.2%. Treatment-related adverse events were also similar in both groups (41%).
“We have a new treatment that has a chance to improve response and survival for patients with muscle-invasive bladder cancer,” Meeks said. “For patients who want to aggressively fight this cancer we have a new way to do that with minimal increase in toxicity. Our next steps are to determine which tumors will benefit from addition of durvalumab and why it is so effective for stage II to III bladder cancer so we really have more work to do.”
Dr. David VanderWeele associate professor of medicine (hematology and oncology) at Feinberg served as local principal investigator for NIAGRA at Northwestern Medicine.
This work was supported by AstraZeneca. The study’s corresponding author Dr Thomas Powles from Barts Cancer Institute at Queen Mary University London will present findings at European Society for Medical Oncology’s 2024 Annual Meeting.