Pembrolizumab Plus Lenvatinib in Metastatic Renal Cell Carcinoma: Real-world Prognostic Factors.

BACKGROUND/AIM: Pembrolizumab plus lenvatinib is first-line treatment for metastatic renal cell carcinoma (mRCC) with favorable outcomes. However, clinicopathological factors associated with treatment outcomes are unclear. We evaluated the effectiveness and safety of pembrolizumab plus lenvatinib, and explored factors associated with progression-free survival (PFS) in a Japanese multicenter cohort.

PATIENTS AND

METHODS

We retrospectively analyzed 160 patients with mRCC who received first-line pembrolizumab plus lenvatinib. We assessed objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), treatment exposure, and adverse events. Factors associated with PFS were evaluated using Cox proportional hazards models.

RESULTS

The ORR and DCR in the overall cohort were 66% and 91%, respectively. Median PFS was 35 months, whereas median OS was not reached. DCR was significantly higher in patients with prior primary tumor resection (98% vs. 86%, p<0.01), metachronous metastasis (98% vs. 88%, p=0.03), and no high-risk metastasis (96% vs. 84%, p=0.01). Any-grade adverse events and grade ≥3 adverse events occurred in 85% and 55% of patients, respectively. Pembrolizumab and lenvatinib were discontinued because of adverse events in 23% and 22% of patients, respectively. In multivariable analysis, clear-cell histology was independently associated with longer PFS [hazard ratio (HR)=0.40, 95% confidence interval (CI)=0.21-0.72], whereas multiple metastatic organs were independently associated with shorter PFS (HR=1.91, 95%CI=1.07-3.37).

CONCLUSION

First-line pembrolizumab plus lenvatinib showed favorable activity and manageable toxicity in real-world practice. Histologic subtype and metastatic extent were independently associated with PFS.