Doublet Therapy Versus Monotherapy for Patients With Metastatic Chromophobe RCC

Sahil D. Doshi, MD, and colleagues at Memorial Sloan Kettering Cancer Center designed a retrospective analysis of patients with metastatic chromophobe renal cell carcinoma (ChRCC) to better understand the effects of first-line systemic therapy.

Results are being presented at the 2024 American Society of Clinical Oncology Annual Meeting.

ChRCC represents approximately 5% to 10% of all renal cell carcinomas, and there is a paucity of clinical trial data to guide systemic therapy decisions for metastatic disease. Previous phase 2 clinical trials have shown that targeted agents inhibiting vascular endothelial growth factor receptor and mammalian target of rapamycin have comparable efficacy in ChRCC compared with conventional RCC, while immune checkpoint inhibitor (IO)-containing regimens may be less effective in ChRCC compared with other RCC subtypes. Large-scale studies of patients with ChRCC are needed.

This retrospective study sampled 99 patients with metastatic ChRCC from 3 academic centers, of whom 62% were male, 44% had sarcomatoid features, and 33% had favorable risk according to the International mRCC Database Consortium. Baseline characteristics and treatment outcomes were taken from electronic health record review. Researchers categorized the patients into 4 treatment categories:

1. IO plus targeted therapy doublets (eg, lenvatinib plus pembrolizumab)
2. Pure IO monotherapy and doublets (eg, ipilimumab plus nivolumab)
3. Targeted therapy doublets (eg, lenvatinib plus everolimus)
4. Targeted monotherapy (eg, sunitinib)

Researchers calculated time to treatment failure (TTF) of first-line systemic therapy and overall survival (OS).

Dr. Doshi and colleagues found that the median TTF and 18-month OS rates were 15 months and 80% for the IO plus targeted doublets group, 7 months and 83% for the pure IO monotherapy and doublets group, 17 months and 65% for the targeted doublets group, and 5 months and 58% for the targeted monotherapy group.

Importantly, they noted that treatment with any doublet containing a targeted agent compared with targeted monotherapy led to a superior median TTF (15 vs 5 months, respectively; hazard ratio [HR], 0.48; 95% CI, 0.29-0.80; P=.005) and OS (56 vs 23 months, respectively; HR, 0.56; 95% CI, 0.30-1.04; P=.07).

While 11 patients had ongoing treatment at the time of the analysis, 64% had discontinued treatment due to disease progression and 25% had discontinued treatment due to toxicity.

“In this observational analysis, patients with targeted doublet regimens had a higher median TTF and OS compared [with] those receiving monotherapies,” study authors concluded. “We continue to build on this dataset and plan to conduct progression-free survival analysis.”