In an analysis of 1,084 patients with metastatic renal cell carcinoma (mRCC) performed by the international metastatic renal cell database consortium (IMDC), the presence of lung metastases, cytoreductive nephrectomy performed after diagnosis of metastatic disease and before first-line therapy and better IMDC risk group were associated with a higher probability of response to first-line immunotherapy combination regimens. The findings were presented by Dr Vishal Navani of the Tom Baker Cancer Center, University of Calgary in Calgary, Canada and IMDC colleagues at 2022 ASCO Genitourinary Cancers Symposium (17-19 February 2022, San Francisco, CA, US & Online).
The IMDC investigators sought to characterise clinical variables and their association with investigator assessed best overall response to first-line immunotherapy combination regimens in patients with mRCC. They retrospectively identified patients treated with first-line ipilimumab/nivolumab or approved immunotherapy/vascular endothelial growth factor (VEGF) inhibitor combinations.
Patients were classified, per RECIST v1.1, as responders, defined as those with complete response (CR) or partial response (PR) or non-responders, defined as those with stable disease (SD) or progressive disease (PD). Logistic regression was used to adjust for IMDC criteria.
From 1084 patients included in analysis, 794 (73%) received ipilimumab/nivolumab and 290 patients (27%) received immunotherapy/VEGF inhibitor combinations, in particular axitinib/pembrolizumab, cabozantinib/nivolumab, axitinib/avelumab, lenvatinib/pembrolizumab.
Favourable, intermediate and poor IMDC risk comprised 147 patients (16%), 517 patients (55%) and 272 patients (29%) respectively.
Among 898 patients with evaluable responses, 37 patients (4%) achieved a best response of CR, 343 patients (38%) achieved PR, 315 patients (35%) achieved SD and 203 patients (23%) had PD.
Corresponding median overall survival from time of initiation of first-line treatment was not reached, 55.9 months, 48.1 months, and 13 months respectively (logrank p < 0.0001).
In a multivariable model, lung metastases (odds ratio [OR] 1.71) and cytoreductive nephrectomy (OR 1.47). retained independent association with response, after adjustment for IMDC criteria.
Factors not associated with response included with univariable p values: gender (p = 0.58), age (p = 0.06), sarcomatoid histology (p = 0.99), smoking status (p = 0.39), liver (p = 0.63) and brain (p = 0.12) metastases.
The analysis also confirmed the predictive value of IMDC prognostic risk category: the likelihood of response to first-line therapy was significantly higher among patients in the favourable-risk group (OR 2.44).
The authors commented that further work is warranted to identify reliable predictors of response to guide treatment selection and patient counselling.
The study was sponsored by the Alberta Cancer Foundation.
Navani V, Ernst MS, Wells C, et al. Predictors of objective response to first-line immuno-oncology combination therapies in metastatic renal cell carcinoma: Results from the international metastatic renal cell database consortium (IMDC). J Clin Oncol 2022;40:(suppl 6; abstr 310). DOI: 10.1200/JCO.2022.40.6_suppl.310