ASCO Reading Room | Persistence of Racial Disparities in Metastatic Renal Cell Carcinoma Outcomes

First-line treatments in metastatic renal cell carcinoma have undergone dramatic changes in recent years. The emergence of five parallel regimens in the first-line setting has created a plethora of choices. Immune checkpoint inhibitor-based combinations represent a major step forward over existing standard antiangiogenic therapies such as sunitinib. A doubling of median progression-free survival and overall survival has been observed, and it follows that early adoption of these therapies would demonstrate a benefit in terms of clinical outcomes.

The paper by Mitch Hayes et al., presented at the 2024 ASCO Genitourinary Cancers Symposium, comprehensively queried the Flatiron database for real-world information on the impact of therapeutic advances in kidney cancer. Results were analyzed by patient-reported race and 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 use of the therapy within 6 months of FDA approval.

The study showed that the 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 were underrepresented, however, and made up only 5.7% of this real-world database. While this percentage is suboptimal, it is still better than the 1% or less representation seen in renal cell carcinoma (RCC) clinical trials.

Asian patients, representing 1.7% of the database population, had the best survival outcomes (HR 0.76, 95% CI 0.56-1.04, P= 0.087). The use of new treatments did not differ by race of patients. These results are remarkable but cannot be considered conclusive because a multivariate analysis incorporating confounding variables such as International Metastatic RCC Database Consortium risk, sites of metastases and socioeconomic status was not performed.

In the case of a therapy with a large benefit, a difference in outcome can be expected if new therapies are adapted early. However, the threshold of magnitude of benefit must be considered before rapidly integrating new treatments. It is not surprising that patients treated in academic centers have demonstrated a better benefit in terms of overall survival. The interaction effect between early adopters of the therapy and oncologists in academic centers must be taken into account.

Academic oncologists are more likely to adopt these therapies early, especially if they have participated in clinical trials of the new agent, giving them a head start and some level of comfort in their use. In large community clinics, the delay associated with a change in pathways and guidelines is likely to impact the time to adoption of new therapies.

For therapies that represent a significant advance, this will likely impact clinical outcomes. However, early adoption may not be effective or essential for all new therapies. Toxicities, cost, and magnitude of efficacy must be considered for a value-based proposition of early use.

In the case of contemporary first-line therapies in advanced RCC, early adoption promises a positive impact on outcomes. With second- and third-line therapies recently approved by the FDA in metastatic RCC, it seems unlikely that early adoption will have a similar impact on clinical outcomes.

It should be noted that early adoption of these treatments requires comprehensive knowledge and education about anticipated toxicities and appropriate management. In addition, accelerated/early FDA approvals may be withdrawn if inadequate efficacy and/or increased toxicity are noted after additional testing in randomized trials. Decisions regarding early adoption should therefore be combined with a value-based risk/benefit assessment in the context of contemporary disease and patient characteristics.

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

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

Read the study here and an interview about it here.