How has FDA label change affected treatment of advanced bladder Ca?

Access to novel therapies early in the regulatory process as a result of the FDA’s accelerated approval program can be valuable for many cancer patients, but the clinicians who are responsible for their care must have heightened vigilance for incoming data and FDA guidance about these drugs that have not gone through the “gold standard” of phase III testing.

Findings from a study investigating treatment utilization for advanced bladder cancer patients indicate that physicians are doing a pretty good job of responding to incoming safety data, said Ravi Parikh, MD, MPP, lead author of the recently published data (JAMA 2019; 322:1209-11).

The study analyzed changes in rates of immunotherapy and chemotherapy use following the FDA label change in the approved indications for pembrolizumab (Keytruda) and atezolizumab (Tecentriq) that limited their use as first-line agents for treatment of advanced bladder cancer in cisplatin-ineligible patients to those with programmed death-ligand 1 (PD-L1) positive tumors. The two immunotherapy agents were originally approved through the accelerated approval program to be used as first-line treatment of any cisplatin-ineligible patients. The change, which was made in June 2018, was prompted by phase III clinical trial data showing patients with PD-L1-negative tumors had decreased survival when treated with the immunotherapies compared with patients receiving platinum-based chemotherapy.

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“We undertook this study because our approach to clinical care of patients with advanced bladder cancer was essentially changed overnight by the FDA label restriction. Even among our study’s co-authors, there was a lot of debate about whether practice should change in the absence of published evidence, and we reasoned we were not the only ones asking this question,” said Dr. Parikh, instructor, medical ethics and health policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

“This was a unique situation with no prior data to guide decisions. Given the recent availability of near-real-time data on prescribing patterns, we had the ability to conduct this unprecedented study looking at whether practice patterns changed after this novel label change.”

The authors used the Flatiron Health database to identify patients with advanced bladder cancer who received at least one line of systemic therapy between Jan. 1, 2016, and Jan. 31, 2019. They analyzed the effect of the FDA label change on the utilization of first-line immunotherapy, platinum-based chemotherapy, and PD-L1 testing at 8 months after the immunotherapy label change. The analysis included data for 1,965 patients, of whom 94% received care in a community practice setting.

“Most cancer patients receive care in community oncology sites, and so we feel that our study population accurately reflects the real-world population,” said Dr. Parikh.

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Using a multivariable logistic regression model, the analysis showed that compared with the date of the label change, immunotherapy use decreased significantly 8 months later by 37.4 % (p<.001). The shift in immunotherapy utilization corresponded with a nearly identical significant increase of 34.4% in the rate of chemotherapy use (p<.001). PD-L1 testing also increased significantly, but only by approximately 13%.

Dr. Parikh said that the main strength of the analysis was its use of a real-time database of patients with cancer that included highly granular information on clinical characteristics. Additionally, it employed a robust quasi-experimental design to try to pinpoint the effect of the policy change rather than measuring other characteristics that could have contributed to the prescribing patterns.

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One of the study’s limitations was that data on PD-L1 testing status were not available for all patients.

“Unfortunately, therefore, we could not assess whether the decline in immunotherapy use was appropriate or not. We hope to be able to investigate that issue in future analyses,” Dr. Parikh said.

Dr. Parikh and colleagues are also planning to analyze data collected after longer term follow-up to try to identify the true “valley” of immunotherapy use for advanced bladder cancer. They also plan to investigate how the policy affects clinical outcomes for bladder cancer patients.

Have your prescribing habits for advanced bladder cancer changed? Let us know at urology_times@mmhgroup.com