Real-World Evaluation of First-Line PAXI Combo

The combination of pembrolizumab and axitinib (PAXI) is an approved first-line combination therapy for metastatic renal cell carcinoma (mRCC). A real-world study based out of Italy by Annalisa Guida, MD, and colleagues sought to evaluate the outcomes of this combination and uncover any relevant revelations of characteristic-based adverse events (AEs) for this immunotherapy combination.

One-hundred-and-seventy patients were treated with PAXI between December 2020 and September 2023. The majority of patients had clear-cell histology (83%), and sarcomatoid feature was present in 33% of cases.

Fifty-five percent of patients had synchronous metastasis, and in 58% of cases, nephrectomy was performed, of which, 27% were cytoreductive and 4% were deferred nephrectomies.

Lung metastases were identified in 106 patients (62%), as well as bone and liver involvement in 66 (38.8%) and 29 (17.1%) patients, respectively.

As stratified by IMDC criteria:

• 32 patients were at favorable risk (18.8%)
• 106 were at intermediate risk (62.4%)
• 32 were at poor risk (18.8%)

At the time of analysis, treatment was ongoing in 49% of patients, and progression occurred in 45%. Median progression-free survival (PFS) was 19.2 months (95% CI, 15-NR). Median follow-up was 19.3 months (range, 1.3-34.5); at the 24-month and 36-month landmark analysis, 62% (95% CI, 53-70) and 58% (95% CI, 47-69) of patients are still alive, respectively.

Disease control rate was achieved in 84.6% of patients; 4.3% reached a complete response, 52% had partial response, and 28.8% had stable disease. Primary progression was observed in 15.3% of patients.

In the multivariate analysis, the prognostic significance of age 65 years or older, no-clear cell history, IMDC score, and AEs and gender interactions as predictors of worse overall survival were confirmed.

“Our findings support the effectiveness and safety of this first-line combination in mRCC and reveal that gender is a prognostic factor in relation to the occurrence of adverse events,” the researchers concluded.