IKCS 2022: Depth of Response Associated with First-Line Immunotherapy-Based Combinations in Metastatic Clear Cell Renal Cell Carcinoma

(UroToday.com) The 2022 IKCS North American annual meeting featured a presentation by Dr. Kelly Fitzgerald discussing depth of response associated with first-line immunotherapy-based combinations in metastatic clear cell renal cell carcinoma (RCC). First-line treatment options for clear cell RCC include ipilimumab with nivolumab (IO/IO) or several VEGFR-targeted therapies in combination with a PD-1 inhibitor (TKI/IO). Depth of response has been proposed as a predictor of sustained benefit from IO-based therapies. At the 2022 IKCS North American meeting, Dr. Fitzgerald and colleagues examined the relationship between depth of response and overall survival in patients receiving first-line IO/IO vs TKI/IO for metastatic clear cell RCC.

This study was a retrospective analysis of patients treated for clear cell RCC with first-line IO/IO or TKI/IO at Memorial Sloan Kettering Cancer Center between January 1, 2014 and December 30, 2020. Depth of response was defined as the nadir of tumor shrinkage by RECIST 1.1 criteria. Partial response groups were defined as PR1 (80-99%), PR2 (60-79%), and PR3 (30-59%). Overall survival from the start of first-line therapy to death or last follow-up is estimated with the Kaplan-Meier method and reported for each depth of response group.

There were 173 patients that received first-line IO/IO (n = 90) or TKI/IO (n = 83). Differences in the IO/IO group versus TKI/IO include more patients with brain metastases (9% vs 0, p = 0.007) and intermediate-poor IMDC risk (88% vs 68%, p = 0.007), and fewer with prior nephrectomy (67% vs 86%, p = 0.005):

immunotherapy based combinations chart 

Objective response rates for IO/IO and TKI/IO groups were respectively 38% (95% CI 28-49%) and 65% (95% CI 54-75; p < 0.001):

first line response rate pie chart 

Overall survival by depth of response in the overall cohort and by first-line treatment group are as follows:

group result charts 

The 24-month survival estimates for the overall cohort were: complete response group (94%, 95% CI 65-99%), PR1 group (100%), PR2 group (94%, 95% CI 63-99%), PR3 group (79%, 95% CI 57-91%), stable disease group (57%, 95% CI 42-70%), and progressive disease group (52%, 95% CI 29-71%). The best response to first-line therapy is as follows:

change from baseline graph 

Finally, outcomes on first- and second-line therapy are as follows:

first and second line results chart 

Dr. Fitzgerald concluded this presentation by discussing depth of response associated with first-line immunotherapy-based combinations in metastatic clear cell RCC with the following concluding statements:

  • Patients receiving first-line IO/IO or TKI/IO therapies had a significant difference in the distribution of radiographic depth of response groups, with more complete responses and partial responses seen in the TKI/IO group and more stable disease and progressive disease seen with IO/IO
  • Patients whose best response was complete response, PR1, or PR2 had higher 24-month overall survival than patients with PR3, stable disease, or progressive disease
  • Depth of response may be a useful radiographic biomarker for early prediction of long-term responses to IO combinations

Presented by: Kelly N. Fitzgerald, MD, Medical Oncology Fellow, Memorial Sloan Kettering Cancer Center, New York, NY

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 International Kidney Cancer Symposium (IKCS) Annual Hybrid Meeting, Austin, TX, Fri, Nov 4 – Sat, Nov 5, 2022.

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