(204) Real-World Outcomes Associated with Subsequent-Line Therapy for Metastatic Renal Cell Carcinoma: An Institution’s Experience

Poster Abstract:

Background:
Renal cell carcinoma (RCC) accounts for approximately 3% of all adult cancers with 60 - 80% being of clear cell histology. Historically, metastatic clear cell RCC was treated with various combinations of chemotherapy, radiation, and hormonal therapy. However, clinical observations and research provided evidence that patients with clear cell RCC lacked sensitivity to chemotherapy. Further research identified high response rates to VEGF tyrosine kinase inhibitors (TKIs), which quickly phased out traditional chemotherapy. Recently, first-line recommendations have shifted again due to results of the KEYNOTE-426 and CLEAR trials, which demonstrated significant improvements in progression-free survival and overall survival with the combination of immunotherapy and a TKI compared to TKI alone. However, limited evidence exists to establish the preferred second-line regimen upon progression through first-line treatment. The current recommended second-line options have earned their positions due to extrapolation from their use in the upfront setting and in the second-line setting following first-line anti-angiogenesis therapy. Additionally, the type and severity of adverse events of second-line agents following first-line immunotherapy-based combinations have not been clearly described. The purpose of this retrospective, observational study is to describe the efficacy and safety outcomes associated with subsequent systemic therapy in patients with metastatic renal cell carcinoma upon progression through first-line immunotherapy-based combination treatment.

Objectives:
The primary objective is to determine the 6-month progression-free survival after switching to subsequent therapy following first-line immunotherapy-based combination treatment. Secondary objectives will assess the tolerability and adverse effects experienced on second-line therapy.

Methods:
This study is a single-center, retrospective, observational study. Adult patients were included if they received at least one dose of second-line treatment following progression on first-line immunotherapy-based combination treatment between January 1st, 2019 to February 28th, 2023. Exclusion criteria included metastatic RCC of non-clear cell histology, receipt of a first-line regimen that does not include immunotherapy, and transfer of care to an outside institution without shared electronic medical records.

Results:
Of the 92 RCC patients that were reviewed, 36 patients met inclusion criteria. The median age of the study population was 61 with 25 (69.4%) of the patients being male. The final results and statistical analysis are pending.

Discussion/

Conclusion:
In the absence of comparative trials between second-line options for metastatic clear cell RCC, our study is poised to highlight potential heterogeneity in selection of agents, demonstrate the different efficacy and safety outcomes associated with current practice, and shed further light on optimal treatment sequencing in the second-line setting.

References (must also be included in final poster): 1. Hutson TE. Renal cell carcinoma: diagnosis and treatment, 1994-2003. Proc (Bayl Univ Med Cent). 2005;18(4):337-340. doi:10.1080/08998280.2005.11928093
2. Dutcher JP, Flippot R, Fallah J, Escudier B. On the Shoulders of Giants: The Evolution of Renal Cell Carcinoma Treatment-Cytokines, Targeted Therapy, and Immunotherapy. Am Soc Clin Oncol Educ Book. 2020;40:1-18. doi:10.1200/EDBK_280817
3. Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21(12):1563-1573. doi:10.1016/S1470-2045(20)30436-8
4. Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716
5. National Comprehensive Cancer Network (NCCN) Guidelines. Kidney Cancer. V1.2024