Primary Renal Tumour Response in Patients Treated with Nivolumab and Ipilimumab for Metastatic Renal Cell Carcinoma: Real-world Data Assessment

Abstract

Following CARMENA and SURTIME, patients with metastatic renal cell carcinoma (mRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate and poor risk receive systemic therapy with the primary tumour (primary) in place, with the option of deferred cytoreductive nephrectomy (CN) in responding patients. We retrospectively analysed the safety and efficacy of first-line nivolumab/ipilimumab in 71 primary mRCC patients (42.3% IMDC poor risk; 43.6% with more than three metastatic sites). The baseline mean primary diameter was 9.3 cm and median follow-up was 11.5 mo. Of 69 patients with at least one follow-up computed tomography scan, 23 (33.3 %) had a partial response (PR) of the primary after a median of 4.8 mo, which was associated with a 91.3% overall response rate at metastatic sites (MSs) and absence of progressive disease, irrespective of the IMDC risk. The complete response (CR) rate at MSs ( n = 7 [10.1%]) is similar to the CR rate in CheckMate 214. Thirteen deferred CNs were performed (18.8%) after a median of 13 mo, rendering four patients disease free. Only 4.3% of primaries progressed; grade 3–4 immune-related adverse events occurred in 31.9%. Irrespective of the IMDC risk, patients with a PR in the primary had a 1-yr overall survival rate of 89% versus 67% in those without ( p = 0.012). Patient summary Patients with metastatic kidney cancer receiving immunotherapy with nivolumab and ipilimumab had superior response at metastatic sites and better survival irrespective of International Metastatic RCC Database Consortium (IMDC) risk.

The Role of Cytoreductive Nephrectomy in Renal Cell Carcinoma with Sarcomatoid Histology: A Case Series and Review of the Literature

“…From this point of view, it seems more convenient to start with systemic therapy to achieve disease control; on the other hand, the window of opportunity for removing the primary tumor can be missed irreversibly. Interestingly, a retrospective analysis of 71 mRCC patients treated with ipilimumab and nivolumab upfront with the option of deferred CN in responding patients showed a 33.3 % response rate in the primary site and a 91.3% overall response rate at metastatic sites regardless of the prognostic group [ 45 ]. CN was performed in 18.8% of the patients after a median time of 13 months [ 45 ].…”

“…Interestingly, a retrospective analysis of 71 mRCC patients treated with ipilimumab and nivolumab upfront with the option of deferred CN in responding patients showed a 33.3 % response rate in the primary site and a 91.3% overall response rate at metastatic sites regardless of the prognostic group [ 45 ]. CN was performed in 18.8% of the patients after a median time of 13 months [ 45 ].…”

Partial Nephrectomy for Metastatic Renal Cell Carcinoma: Con

“…Despite the assumption that the overall indication for deferred CN may therefore increase, overall response rates to systemic therapy range from 46% to 60%, with complete responses occurring in only one in every ten patients [6] . Real-world data for patients treated with nivolumab and ipilimumab with the primary tumour in place revealed that only 13% were offered deferred CN [7] . Thus, cytoreductive surgery for the primary tumour as a procedure, whether upfront or deferred, has become a rare intervention for which to select candidates for PN.…”

“…An additional argument against PN in the metastatic setting is the complexity of primary tumours. In metastatic disease, primary tumours are 9 cm in diameter on average [2] , [3] and although downsizing can be expected on ICI combination therapy [7] , [8] , a reduction in primary tumour diameter of ≥30% occurs in only one-third of patients [8] . According to real-world data for patients in the intermediate IMDC group treated with dual ICI and the primary tumour in place, the baseline median primary tumour size was 14 cm, which decreased by a median of only 12.9% [7] .…”

“…In the retrospective series of patients treated with the primary tumour in place, some dramatic responses have been described following ICI combination therapy, with primary tumour downsizing of >70% to <4 cm in diameter [7] , [8] . We acknowledge that it is tempting to consider PN in these individual cases, but it should be noted that the evidence for this approach is poor.…”