The use of enfortumab vedotin with pembrolizumab (an anticancer therapy combination) for U.S. adults with bladder cancer who are ineligible for traditional chemotherapy before having their bladder surgically removed is likely cost-effective from a Medicare perspective compared to having the surgery alone, according to the findings of a health economic modeling study based on results from the KEYNOTE-905/EV-303 trial.

These findings recently published in JAMA Network Open.

The researchers found that the upfront costs of this treatment combination are offset by long-term reductions in healthcare spending. After reviewing the total costs and benefits, specifically assessed with years lived in perfect health, throughout a 10-year period, the researchers found that the treatment combination added 1.3 years spent in perfect health. The cost for this quality life gained, or quality-adjusted life-years (QALY), was $72,460, which fell below a common $100,000 threshold that was used to assess cost-effectiveness. In this case, if a therapy costs $100,000 or less for the benefits of adding an average year lived in good health, it was considered cost-effective.

“These estimates lend additional support to this new treatment as both the clinical standard of care, and also as an economically reasonable and responsible option,” says Zhuo Tony Su, M.D., the first study author and a recent graduate of the urology residency program at the James Buchanan Brady Urological Institute at Johns Hopkins Medicine.

Bladder cancer, which accounts for 4% of all new cancer cases in the U.S., has varying survival rates based on its stage. Five-year survival rates can surpass 90% when the cancer is confined in superficial cell layers lining the bladder. These rates can decrease as the stage advances. For example, five-year survival rates are 73% for cancer invading the muscle layer of the bladder (muscle-invasive bladder cancer) and less than 10% when the cancer spreads to other organs.

Treatment options introduced in recent years, including those supported by research at Johns Hopkins Medicine, have helped significantly extend survival for patients with bladder cancer. They have marked pivotal advancements in science and medicine, but have also come with high upfront costs for insurers.

“We have these new drugs offering significant clinical benefits to our patients,” says Su. “Yet, physicians were curious, ‘What is the cost to the healthcare system? Are we being cost-conscious enough?’”

These questions served as the goal for conducting a health economic evaluation to assess the cost-effectiveness of combination enfortumab vedotin and pembrolizumab for adults ineligible for or who declined cisplatin-based chemotherapy, which is traditionally the standard therapy before bladder surgery for patients with muscle-invasive bladder cancer. To create this model, the researchers used results from 344 participants in the landmark KEYNOTE-905/EV-303 trial.

Those in the KEYNOTE-905/EV-303 trial who received the combination regimen before and after surgery were considered the intervention group, while those who had surgery alone (radical cystectomy) without the combination treatment were the control. After two years, participants who received the combination treatment before and after surgery were more likely to remain in remission (75% versus 39%) and live longer (80% versus 63%).

To assess the cost-effectiveness of this combination treatment approach, the investigators used projected modeling estimates to assess outcomes of participants after five years, 10 years and for a lifetime. (The average age of simulated participants was 73.)

The upfront costs for treatment were $336,907 for the intervention group compared to $27,974 for the control group. Healthcare costs throughout 10 years were $412,160 for the intervention group and $317,513 for the control, which resulted in a difference of $94,647. This estimate was also projected to provide 1.3 years lived in good health with a QALY of $72,460.

After five years, people in the intervention group had a predicted net gain of seven months of years lived in good health compared to the control. This equated to $229,658 for each QALY.

Lifetime estimates predicted an extra 1.7 years lived in good health with a QALY of $59,218.

“Overall, we found that these therapies are generally cost-effective when we factor in long-term health outcomes and healthcare costs that accrue over years,” says Max Kates, M.D., the senior study author, director of the urological oncology division at the Brady Urological Institute, and co-director of the Greenberg Bladder Cancer Institute.

The researchers note there are additional limitations and variables to consider. For example, these estimates may vary as long-term outcomes of patients from the KEYNOTE-905/EV-303 trial are observed. As research advances, additional information — such as new technologies assessing residual disease risk and predicting how a person may respond to specific treatments — will further inform who may benefit most from these therapies at different points in care.

To learn more about the research, visit jamanetwork.com/journals/jamanetworkopen/fullarticle/2855494.