Upfront TKI for Bone-Predominant RCC Tops Single-Agent Immunotherapy

LOUISVILLE, Ky. — Patients with bone-predominant metastatic renal cell carcinoma (RCC) appeared to have better outcomes when they started treatment with a targeted drug, results of a small retrospective review suggested.

Median overall survival (OS) increased from 19.3 months with upfront immune checkpoint inhibition (ICI) to 41.3 months when a tyrosine kinase inhibitor (TKI) was used first. Median progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) all favored TKI treatment.

The retrospective data require validation in prospective studies, reported Lingbin Meng, MD, PhD, of Ohio State University Comprehensive Cancer Center in Columbus, at the International Kidney Cancer Symposium.

“These results suggest TKI-containing front-line therapy may be the preferred treatment option for bone-predominant metastatic RCC,” Meng and colleagues concluded in a poster presentation. “Limitations of this study include its retrospective design and small sample size. Larger, prospective studies are needed to validate these results and to optimize treatment strategies for bone-predominant metastatic RCC.”

The study covered the years 2008 to 2021, which did not include more recent combination strategies such as nivolumab (Opdivo) plus ipilimumab (Yervoy) and pembrolizumab (Keytruda) plus lenvatinib (Lenvima), said invited discussant Arpita Desai, MD, of the University of California San Francisco.

“They found that the clinical efficacy was better with TKIs as compared to immunotherapy in patients with bone-predominant disease,” she said. “They looked at different variables — age, gender, performance status, risk status, number of metastatic sites — and basically they found the same thing.”

“They did not mention what kind of TKIs were used. They just grouped them all together,” Desai added. “So basically, frontline TKI-based regimens are better in patients who have bone metastasis compared to a purely immunotherapy-based regimen.”

Offering additional context to the findings, poster co-moderator Priyanka Chablani, MD, of the University of Pittsburgh, noted that the CLEAR trial showed superiority for the pembrolizumab/lenvatinib combination versus sunitinib (Sutent) across subgroups, including patients with bone-predominant disease.

Bone-predominant disease is associated with significant comorbidities and poor prognosis, Meng and colleagues noted in their introduction. Optimal treatment remains controversial because patients with bone-predominant RCC are often excluded from clinical trials due to challenges in measuring treatment response. High angiogenesis signatures in bone-predominant disease suggest patients may respond favorably to TKIs.

To examine “real-world” outcomes in bone-predominant RCC, the investigators reviewed records for 771 patients with advanced RCC, including 143 with bone metastases. Subsequently, they identified 69 patients with bone-predominant disease, 40 of whom started treatment with a TKI-containing regimen and 29 who received an ICI. Baseline characteristics were comparable between the two groups.

Meng and colleagues compared outcomes in the two groups with respect to ORR, PFS, and OS. The results showed a statistically significant 22-month difference in median OS favoring upfront TKI therapy (P=0.036). The analysis of PFS yielded a trend in favor of TKI treatment (7.9 vs 4.9 months, P=0.075).

The TKI group had an ORR of 22.9% as compared with 12% for the ICI group, a difference that did not achieve statistical significance (P=0.332). An additional 37.1% of patients treated with TKIs and 40% treated with ICIs had stable disease, resulting in a DCR of 60% versus 52% (P=0.603).

A univariate analysis of predictors of OS identified two statistically significant factors: treatment with an ICI versus TKI (HR 1.96, 95% CI 1.03-3.71, P=0.04) and clear cell histology versus other (HR 0.30, 95% CI 0.13-0.74, P=0.009). Age, gender, performance status, risk status, prior nephrectomy, and number of metastatic sites did not significantly affect the survival likelihood.

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