Patients with clear cell (cc) renal cell carcinoma (RCC) demonstrated a better response to tremelimumab compared with patients with non–clear cell (ncc) histology who underwent cryoablation, according to a pilot study presented at the 19th Annual Meeting of the International Kidney Cancer Symposium (IKCS 2020).
Approximately 25% to 30% of patients with RCC have ncc histology, but it is not yet known how anti–CTLA-4 antibodies affect the tumor microenvironment in this setting.
The pilot study (ClinicalTrials.gov Identifier: NCT02626130) randomly assigned patients with RCC to receive tremelimumab plus surgery or tremelimumab with cryoablation. Patients who responded to initial treatment were eligible for tremelimumab maintenance. These data are from a post hoc analysis, in which patients were stratified by cc or ncc histology. In the post hoc analysis, there were 18 patients with ccRCC and 11 patients with nccRCC.
Patients with ccRCC demonstrated a numerically longer progression-free survival (PFS), with a median of 5.5 months compared with 2.9 months among patients with ncc histology (hazard ratio [HR], 0.44; 95% CI, 0.18-1.07), which was not significant. The 12-month PFS was also higher at 27.8% among patients with ccRCC compared with 9.1% among patients with nccRCC.
Overall survival (OS) was significantly different between the histologies, with a median of 38.6 months for patients with ccRCC compared with 16.4 months for patients with nccRCC (HR, 0.32; 95% CI, 0.1-1.0).
“We now have 3 patients who are well past 2 years who have not required subsequent therapy, and zero of these patients are still receiving therapy on study,” Mathew T. Campbell, MD, MS, of the UT MD Anderson Cancer Center, and presenter of the poster, said.
Tissue-based immune monitoring data demonstrated that the IFN-γ signaling pathway was enriched in ccRCC compared with nccRCC. CyTOF also showed that patients with ccRCC had elevated CD45- and CD3-positive cells in posttreatment tissue, which was confirmed by immunohistochemistry.
Dr Campbell noted that signals of an innate immune response were present in nccRCC samples, but not to the extent needed to initiate an adaptive response.
Dr Campbell concluded that “the baseline tumor microenvironment of clear cell disease is more favorable for anti–CTLA-4 therapy as compared to non-clear cell histologies.”
Campbell MT, Matin SF, Tam AL, et al. A pilot study of tremelimumab with or without cryoablation in patients with metastatic renal cell carcinoma (mRCC): a post hoc analysis of patients with clear cell (cc) versus non-clear cell (ncc) histologies. Presented at: 19th Annual Meeting of the International Kidney Cancer Symposium (IKCS 2020); November 6-7, 2020. Abstract NAS120.
This article originally appeared on Cancer Therapy Advisor