Effect of Treatment of Residual Disease After Immunotherapy-Based Combinations on Complete Response Rate of Patients With Metastatic Renal Cell Carcinomas

Introduction: Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement.

Materials and methods: We included retrospectively all consecutive mRCC patients treated in first-line setting at the Institut de Cancérologie Strasbourg Europe with an ICI-based combination involving ICI or TKI, either alone or with added local treatment of residual disease. Patients were characterized according to IMDC risk. Radiologic response was defined according to RECIST v1.1.

Results: We enrolled 80 mRCC patients treated with ICI-based combinations between May 2015 and May 2022. The median age was 63 years. Regarding IMDC risk, there were 12 favourable (15%), 50 intermediate (63%), and 18 poor-risk (22%) patients. Forty-seven patients (59%) received ICI + ICI, 24 (30%) received ICI + TKI, and 9 (11%) received another ICI-based therapy. In total, 8 achieved CR (10%), 36 patients (45%) achieved partial response, 23 (29%) achieved stable disease and 12 achieved progressive disease (15%) as the best response with systemic therapy alone. By adding local treatment of residual disease, 11 additional patients (14%) achieved radiological NED. Residual disease resected sites included kidney (n = 6), lymph nodes (n = 5), lung metastases (n = 2) and liver metastases (n = 1).

Conclusions: The resection of residual disease after first-line ICI-based therapy is associated with improved CR rate (CR + NED) in patients with mRCC. These results need to be validated in prospective trial.

Patient summary: In recent years, the advent of immunotherapy has radically changed the management of patients with metastatic kidney cancer. Approximately 10% to 18% of these patients using immune checkpoint inhibitor (ICI)-based combinations no longer have detectable disease on CT scans (complete response). There are currently few data on the use of treatment of residual disease to increase the number of patients in complete response. In this retrospective study, the complete response rate with ICI-based treatment was 10%. When local treatment was added, the number of patients with a complete response increased to 24%. This strategy could increase the number of patients with a prolonged complete response in the future.