Immunotherapy in the Frontline Demonstrates Promise in mRCC With Poor Performance Status


Patients with metastatic renal cell carcinoma and a performance status of 2 or more experienced promising clinical activity from treatment with nivolumab/ipilimumab and pembrolizumab/axitinib.

Treatment with nivolumab (Opdivo) plus ipilimumab (Yervoy) and pembrolizumab (Keytruda) plus axitinib (Inlyta) yielded comparable and promising safety and efficacy in patients with metastatic renal cell carcinoma (mRCC) and a performance status of 2 or greater, according to data that were presented at 2022 Genitourinary Cancers Symposium.

At a median follow-up of 11.1 months, the overall objective response rate (ORR) was 27%; the ORR was numerically higher with pembrolizumab/axitinib (42%) vs nivolumab/ipilimumab (20%) but did not reach statistical significance (P = .157).

The overall median progression-free survival (PFS) was 4.4 months, and the median overall survival (OS) was 15.9 months.

“We report the first cohort of performance status ≥2 mRCC patients treated with checkpoint inhibitor combinations in the first-line setting. No significant difference in ORR, PFS, or OS was seen between nivolumab/ipilimumab and pembrolizumab/axitinib,” the study authors wrote in the poster.

Dual checkpoint inhibition is a standard frontline treatment regimen for patients with mRCC. However, patients with a performance status of 2 or greater were not eligible for enrollment in the pivotal trials, leaving the efficacy and safety of these regimens unknown in this population.

As such, a multicenter study was performed, evaluating 56 patients with mRCC with a performance status of 2 or greater treated with the frontline combination of nivolumab and ipilimumab (n = 36) or pembrolizumab and axitinib (n = 20) across 13 institutions between 2017 and 2021.

ORR, disease control rate (DCR), PFS, OS, and grade 3 or greater treatment-related adverse effects (TRAEs) were evaluated. The association between Lung Immune Prognostic Index (LIPI) score and ORR, PFS, and OS was also evaluated.

The median age at diagnosis was 64 years (range, 31-83). Most patients were male (n = 38; 67.9%); 16 (28.6%) had undergone nephrectomy, and 40 (71.4%) had synchronous metastatic disease at diagnosis.

Most patients had a good LIPI score (n = 18; 32.1%), followed by intermediate (n = 13; 23.2%) and poor (n = 5; 8.9%); 36 patients’ data was not applicable. Additionally, most patients had a Fuhrman grade of III (n = 21; 37.5%), followed by II (n = 15; 26.8%), IV (n = 5; 8.9%), and I (n = 2; 3.6%).

A total of 19 (33.9%) and 37 (66.1%) patients had intermediate and poor risk, respectively, according to the International Metastatic RCC Database Consortium (IMDC). A total of 50 patients (89.3%) had clear cell RCC, and 4 patients (7.1%) had sarcomatoid features.

At data cutoff, 45% of patients had died.

Additional results showed that no significant difference in median OS (P = .362), median PFS (P = .536), or the rate of grade 3 or greater TRAEs was found between the pembrolizumab/axitinib and nivolumab/ipilimumab regimens (24% vs 22%, respectively; P =1.0). Moreover, no significant difference in median OS or median PFS was seen, according to IMDC risk score (P = .818).

The DCR was 58% in the pembrolizumab/axitinib group vs 43% in the nivolumab/ipilimumab group (P = .440).

Notably, LIPI score was significantly associated with OS (poor LIPI: HR, 8.18; P = .004) and PFS (intermediate LIPI: HR, 2.4; P =.048; poor LIPI: HR, 8.59; P <.001). Moreover, LIPI predicted for response in patients who received nivolumab/ipilimumab (P = .024).

“LIPI score was significantly associated with OS and PFS and was predictive of ORR in the nivolumab/ipilimumab group,” the study authors concluded. “Prospective studies are needed to confirm these results.”


Carril-Ajuria L, Colomba E, Romero-Ferreiro C, et al. Efficacy of first-line combination therapy in metastatic renal cell carcinoma (mRCC) patients (pts) with poor performance status (PS). J Clin Oncol. 2022;40(suppl 6):320. doi:10.1200/JCO.2022.40.6_suppl.320

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