A. Craig Lockhart, MD

A. Craig Lockhart, MD, Professor of Medicine, University of Miami Sylvester Comprehensive Cancer Center, applauded the study for making patient-reported outcomes a prespecified endpoint and described the value of having this information. Dr. Lockhart was the invited discussant. “The U.S. Food and Drug Administration defines patient-reported outcome as any report of the status of a patient’s health that the patient directly reports to you. It’s not coming from the patient and then being translated through the clinical trials team or the investigator. This is important because clinicians tend to underestimate how severe a particular side effect can be. This is coming directly from the patient…. These data from patients are very good and may improve the risk/benefit assessment when we are trying to decide whether a new therapy is meaningful or not.”

Patient-reported outcomes add value to clinical trials, continued Dr. Lockhart. The data inform how different therapies being compared will impact particular toxicities and how these side effects can be ameliorated by various interventions. Patient-reported outcomes can also be used in screening for eligibility for trials and can help explain treatment dropouts—another factor often underreported in studies. Moreover, they can add information in evaluating the health-related economic value of a drug.

“If we have a new treatment that’s very expensive, the observation of great patient-reported outcomes can add some economic impetus to suggest that, despite its expense, a given treatment is really having an impact on patients’ quality of life,” he explained.

IMbrave150 Data: ‘Clinically Meaningful’

Dr. Lockhart noted that the IMbrave150 investigators “checked many of the boxes” for the optimal use of patient-reported outcomes. They identified these outcomes as a key endpoint, described the underlying hypothesis, and provided evidence validating the outcomes and their formal measurement. He recommended that the published manuscript include the statistical approach for dealing with missing data and acknowledge the specific limitations of the patient-reported outcomes that were provided. “But they’re off to a pretty good start here,” he said.

As for the specific findings reported by Dr. Galle, Dr. ­Lockhart assessed a slower deterioration in quality of life and less decline in physical function as not only being statistically significant, but clinically meaningful. “When we look at the forest plot, almost everything except jaundice appears to be clearly on the side of atezolizumab and bevacizumab, even in the subgroup analysis. Overall, the patient-reported outcomes correspond with the progression-free and overall survival data that were previously presented for IMbrave150,” he added. “Again, this is reassuring that we’re not only seeing improvements in performance—as in overall survival—but the quality-of-life measures seem to follow.”

Finally, according to Dr. Lockhart, the new findings “bolster the case that IMbrave150 is practice-changing. We’ll likely be considering this combination for front-line therapy in our patients.” 

DISCLOSURE: Dr. Lockhart has received institutional research funding from Astellas Pharma, Bristol-Myers Squibb, Merck, and Sarah Cannon Research Institute.