Patients With Non–Clear Cell RCC and Sarcomatoid Differentiation Have Inferior Outcomes to Systemic Therapy

Patients with non–clear cell renal cell carcinoma (RCC) and sarcomatoid differentiation experience inferior outcomes to standard systemic therapy compared with those with clear cell disease, according to data from a study presented during the 2022 Kidney Cancer Research Summit (KCRS).

In the patients with non–clear cell RCC (n = 58) and sarcomatoid differentiation (n = 25), the median overall survival (OS) was 20.7 months (95% CI, 2.8-68.3) vs 70.9 months (95% CI, 49.6-90.6) in the overall population. The hazard ratio (HR) for OS for those with clear cell RCC vs non–clear cell RCC was 1.703 (95% CI, 1.077-2.694; P = .02). The HR for OS in those with sarcomatoid absence or unknown status vs presence was 1.486 (95% CI, 0.827-2.671; P = .19).

“This group remains an unmet need and inclusion in clinical trials to test novel therapeutics should be encouraged,” lead study author Danielle Urman, of the University of California, San Diego (UCSD), School of Medicine and UCSD, and colleagues, wrote in a poster on the findings.

Historical data have indicated that those with RCC and non–clear cell histology as well as those with RCC and sarcomatoid differentiation have inferior outcomes with systemic treatment. However, immunotherapies are starting to demonstrate encouraging activity in those with sarcomatoid differentiation.

In the study presented at the 2022 KCRS, investigators further compared outcomes achieved with systemic treatment in patients with advanced or metastatic RCC who had variant histology and sarcomatoid differentiation and those with clear cell disease.

To do this, information was collected from the UCSD database on 251 patients who had histologically confirmed, advanced or metastatic RCC, who were receiving systemic treatment. These individuals were grouped by histology into the following RCC subsets: clear cell (78%), papillary (5%), chromophobe (4%), XpTranslocation (3%), and unclassified (10%). Within each of these subgroups, investigators noted whether sarcomatoid differentiation was present (12%) or absent (88%).

The primary end point for the research was OS. A key secondary end point was time to treatment failure (TTTF) for each group, which was defined as the time from treatment start to discontinuation due to any reason.

A total of 193 patients with clear cell RCC and 58 patients with non–clear cell RCC were included in the analysis; 25 patients had sarcomatoid differentiation present, and 226 did not. The median age in those with clear cell RCC was 61 years vs 60 years in those with non–clear cell RCC. Across these 2 groups, most patients were male (73.06% vs 65.52%, respectively), White (53.89% vs 60.34%), and had prior nephrectomy (74.09% vs 63.79%).

Regarding disease stage, 26.94% of those with clear cell disease and 29.31% of those with non–clear cell disease had stage 1 disease; in 64.25% and 55.17% of patients, respectively, this information was unknown. Moreover, 60.10% of those in the group of patients with clear cell RCC had at least 1 site of metastasis vs 50.00% of those with non–clear cell RCC.

Regarding International Metastatic RCC Database Consortium risk criteria in the clear cell and non–clear cell groups, patients had intermediate-risk disease (7.25% vs 8.62%, respectively), poor-risk disease (49.74% vs 44.83%), or unknown risk (43.01% vs 46.55%).

In the clear cell group, patients received frontline systemic treatment in the form of a TKI (69.95%), an immunotherapy agent (7.77%), a dual immunotherapy combination (15.54%), an immunotherapy agent plus a TKI (2.59%), or another unspecified treatment (4.15%). In the non–clear cell group, 67.24% of patients received a TKI as first-line systemic treatment, 1.72% had a TKI in combination with another TKI, 6.90% had an immunotherapy agent, 17.24% had a dual immunotherapy regimen, 5.17% had an immunotherapy/TKI combination, and 1.72% received another unspecified treatment.

Additional survival data showed that in those with papillary RCC, the median OS was 75.0 months (95% CI, 12.3-88.3). In those with chromophobe RCC, the median OS was 25.9 months (95% CI, 24.4-72.0%); the median OS in those with XpTranslocation RCC was 68.3 months (95% CI, 11.3-100.5). In those with unclassified RCC, the median OS was 34.3 months (95% CI, 14.2-INF). Lastly, in those with clear cell RCC and sarcomatoid differentiation, the median OS was 70.9 months (95% CI, 18.6-INF).

The TTTF in the overall population was 7.1 months (95% CI, 5.2-9.0). In those with papillary RCC, chromophobe RCC, XpTranslocation RCC, and unclassified RCC, the TTTF was 8.0 months (95% CI, 3.8-10.7), 2.2 months (95% CI, 0.2-17.0), 6.7 months (95% CI, 2.0-35.3), and 4.7 months (95% CI, 3.4-11.1), respectively. The HR for TTTF in those with clear cell disease vs non–clear cell disease was 1.300 (95% CI, 0.972-1.823; P = .13).

In those with non–clear cell RCC and sarcomatoid differentiation, the TTTF was 17.0 months (95% CI, 1.9-35.3); in those with clear cell RCC and sarcomatoid differentiation, the TTTF was 4.0 months (95% CI, 1.2-5.0). The HR for TTTF in those with sarcomatoid absence or unknown status vs sarcomatoid presence was 1.469 (95% CI, 0.953-2.263; P = .08).

These data are consistent with what has been recorded in previous literature, the study authors concluded.

Reference

Urman D, Deshler L, Weise N, et al. Outcomes of patients with advanced renal cell carcinoma (RCC) with variant histology treated with systemic therapy. Presented at: 2022 Kidney Cancer Research Summit; October 6-7, 2022; Philadelphia, PA. Abstract 44