Real-World Data on Treatment Choices for mccRCC

The therapeutic landscape for metastatic clear-cell renal cell carcinoma (mccRCC) has undergone a paradigm shift with the introduction of immune checkpoint inhibitors targeting programmed cell death protein-1 (PD-1). Studies suggest that PD-1 blockade, alone or in combination with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, was at least comparable to and, in some aspects, more efficacious than traditional vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) in the first-line setting.

And in fact, a recent study explored real-world treatment patterns and their impact on patient outcomes. Here’s a brief recap of that study.

In a large retrospect study, investigators reviewed de-identified electronic health record (EHR) databases to analyze treatment trends and patient outcomes in mccRCC patients across the United States. Patients included in the study were diagnosed with mccRCC between 2011 and 2022 and received treatment with at least one year of follow-up. Patients receiving treatment for two or more malignancies were excluded from the study.

There were 7,923 patients that met eligibility criteria, with 4,561 patients diagnosed between 2011 and 2018 (Group 1) and 3,362 patients diagnosed between 2018 and 2022 (Group 2). The landmark analysis of outcomes was performed one year after discontinuing treatment; those outcomes included progression-free survival (PFS), patients who were initiated on a subsequent line of treatment, and expired patients.

According to the lead author Dr. Galarza Fortuna, findings suggest:

• Shifting Treatment Landscape: The study confirmed a significant shift in first-line treatment patterns. Prior to 2018, TKI monotherapy was the most prevalent treatment at 79 percent. However, since the approval of PD-1 inhibitors post-2018, PD-1 combination therapies emerged as the preferred approach, accounting for 58 percent of treatment patterns.
• TKI Monotherapy Persists in Later Lines: TKI monotherapy remained a common treatment approach for next lines of therapy in both groups.
• Reduced Treatment Burden with Newer Therapies: Patients in Group 1 were more likely to receive multiple lines of therapy compared to Group 2.
• Potential Improvement in Patient Outcomes: The landmark analysis at one year after first-line discontinuation revealed PFS of 32 percent in Group 2 compared to 12 percent in Group 1.

This study reinforces the evolving treatment landscape for mccRCC and highlights the increasing adoption of PD-1 combination therapies. And the reduced number of patients requiring subsequent lines of treatment suggests its improved efficacy or durability of response with these newer regimens.

Additionally, the higher percentage of PFS patients in Group 2 also supports improved survival benefit or extended treatment-free intervals associated with PD-1 combinations. Or at the very least, it supports the utility of PD-1 combination therapies in treating mccRCC.

Ultimately, these findings suggest potential benefits associated with these newer regimens, including reduced treatment burden and improved patient outcomes. Although it's important to note that additional research is necessary to confirm these observations and assess the long-term impact of PD-1-based therapies on outcomes for patients with mccRCC.

References:

Chen J, Zheng Q, Zhu S. et al. Neutrophil to lymphocyte ratio may predict efficacy of anti-PD-1 inhibitors in advanced EGFR-mutant non-small cell lung cancer: retrospective cohort study. Sci Rep. 2024;14:4165. doi: https://doi.org/10.1038/s41598-024-54557-0

Fortuna GG, Jo Y, Chehade CH, et al. Changes in treatment (Rx) patterns and attrition rates in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC). J Clin Oncol. 2024;42 (suppl 16; abstr 4527). doi: 10.1200/JCO.2024.42.16_suppl.4527

Sun L, Zhang L, Yu J, et al. Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: a systematic review and meta-analysis. Sci Rep. 2020;10(1):2083. doi:10.1038/s41598-020-58674-4