IMDC Risk Status, Other Factors Predict Response to Immunotherapy in mRCC

Patients with lung metastases, those who had received cytoreductive nephrectomy, and those in the favorable prognostic risk category were more likely to respond to first-line treatment for metastatic renal cell carcinoma (mRCC), according to a retrospective analysis from the International Metastatic Renal Cell Database Consortium (IMDC).¹

These 3 clinical variables were associated with high probability of partial response (PR) or complete response (CR) to first-line combination immunotherapy for mRCC based on the responses of 1084 patients. Other factors were not shown to be associated with likelihood of response to immunotherapy, including sarcomatoid histology and gender. The results were presented by Vishal Navani, MD, at the 2022 ASCO Genitourinary Cancers Symposium.

Investigators collected data on all patients in who received ipilimumab (Yervoy) plus nivolumab (Opdivo) or immunotherapy plus a VEGF inhibitor in the first line for mRCC. Patients who had received ipilimumab/nivolumab made up 794 (73%) of the 1084 patients, while 290 (27%) had received axitinib (Inlyta) plus pembrolizumab (Keytruda), cabozantinib (Cabometyx) plus nivolumab, axitinib plus avelumab (Bavencio), or lenvatinib (Lenvima) plus pembrolizumab.

Patients were considered responders if they had a PR or CR based on RECIST v1.1 criteria, or non-responders if they had stable disease (SD) or progressive disease (PD). There were significant differences in median overall survival (OS) depending on response to first-line treatment.

Out of 898 patients evaluated, 37 (4%) had a best response of CR, 343 (38%) had PR, 315 (35%) had SD, and 203 (23%) had PD. The median OS for patients with PR was 55.9 months, for SD it was 48.1 months, for PD it was 13 months, and OS was not reached for those with CR.

The variables that were considered included age, gender, clear cell versus non–clear cell RCC, sarcomatoid histology, having received a cytoreductive nephrectomy before first-line therapy, smoking status, the presence of bone, lung, brain, and liver metastases, and IMDC risk prognosis.

There were 147 patients (16%) in the favorable IMDC risk group, 517 (55%) in the intermediate risk group, and 272 (29%) in the poor risk group. In the multivariate analysis, those in the favorable group were more likely to respond with an odds ratio (OR) of 2.44.

Patients who had a cytoreductive nephrectomy were more likely to be responders (OR = 1.47; 95% CI, 1.02-2.11; P = .038), as were patients with lung metastases (OR = 1.17; 95% CI, 1.23-2.37; P = .001). No other factors were associated with response to immunotherapy. According to the investigators, these results were similar when examining only those patients who received ipilimumab/nivolumab.

"Presence of lung metastases, CN and better IMDC risk group are associated with a higher probability of response to 1L immunotherapy combination regimens. Further work to identify reliable predictors of response to guide treatment selection and patient counselling is warranted," the authors wrote in their conclusion.

_Reference:

_{1. 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}