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Front-line therapies in metastatic kidney cancer have undergone dramatic changes in the past few years. The emergence of five regimens in parallel in the front-line setting has created a plethora of choices. The immune checkpoint inhibitor-based combinations represent a big leap of advancement over the previous standard existing antiangiogenic therapies such as sunitinib. Doubling of median progression-free and overall survival was noted, and it follows, therefore, that early adoption of these therapies would demonstrate benefit in clinical outcomes.

, presented at the 2024 ASCO Genitourinary Cancers Symposium, comprehensively queried the Flatiron database of real-world information about the impact of therapeutic advances in renal cancer. The outcomes were analyzed by patient self-reported race, and by early use of novel/contemporary therapies by the treating oncologist.

The Flatiron database includes a mix of academic centers and community practices and is designed to capture real-world treatment practices and outcomes. Early adoption was defined as utilization of the therapy within 6 months of FDA approval.

The study showed that racial disparity persists, with shorter overall survival outcomes for Black patients, although the difference was not statistically significant (HR 1.13, 95% CI 0.98-1.31, P=0.083).

Black patients, however, were under-represented and comprised only 5.7% of this real-world database. Even though this is suboptimal, the percentage is still better than the 1% or less representation seen in renal cell carcinoma (RCC) clinical trials.

Asian patients, comprising 1.7% of the database population, had the best survival outcomes (HR 0.76, 95% CI 0.56-1.04, P=0.087). Novel therapy utilization was not disparate by patient race. These results are noteworthy but cannot be considered conclusive as multivariable analysis incorporating confounding variables such as International Metastatic RCC Database Consortium risk, sites of metastases, and socioeconomic status, was not conducted.

In a therapy with a large magnitude of benefit it is anticipated that a difference in outcome will be seen if novel therapies are adapted early. However, the threshold for the magnitude of benefit should be considered before rapidly incorporating novel treatments. It is not surprising that patients treated in academic centers demonstrated better overall survival benefit. The interaction effect between early adapters of therapy and academic center oncologists needs to be taken into account.

Academic oncologists are more likely to be early adapters, especially if they have participated in clinical trials of the novel agent, giving them a head start and a level of comfort in utilizing these therapies. In large community practices the delay related to a change in pathways and guidelines is likely to impact the time to adopting novel therapies.

For the therapies that represent a significant advance this will likely impact clinical outcomes. However, early adoption may not be impactful or essential for all novel therapies. The toxicities, cost, and magnitude of efficacy have to be taken into account for a value-based proposition of early utilization.

In the case of contemporary frontline therapies in advanced RCC, early adoption portended a positive impact on outcome. With recent second- and third-line FDA-approved therapies in metastatic RCC it seems unlikely that early adoption will yield a similar impact on clinical outcomes.

A note of caution about early adoption is that comprehensive knowledge and education of the anticipated toxicities and appropriate management are required. In addition, the accelerated/early FDA approvals can be withdrawn if inadequate efficacy and/or increased toxicity is noted after further testing in randomized trial settings. So decisions about early adoption have to be paired with consideration of the value-based risk/benefit ratio in the context of contemporary disease and patient characteristics.

In summary, increased representation of minority populations remains an unmet need in the community databases and in clinical trials. For novel regimens with a large magnitude of benefit and manageable toxicities, early adoption has the potential to improve clinical outcomes.

Ulka Vaishampayan, MD, is the Beverly Mitchell MD Research Professor of Medicine, Ambulatory Clinical Chief (Hem/Onc), Director of the MET (Phase I) team, and Co-Leader of the Translational Clinical Research Program at Rogel Cancer Center of the University of Michigan in Ann Arbor.

Read the study here and an interview about it here.