Efficacy and Safety of Pembrolizumab plus Axitinib combination for Metastatic Renal Cell Carcinoma in a Real-World Scenario: Data From the Prospective ProPAXI Study

Background: Pembrolizumab/Axitinib combination is approved as first-line therapy in mRCC. The aim of this study is to evaluate outcomes of PAXI combo in the real-world in Italy. Methods: This is a prospective study including patients diagnosed with mRCC who received combination as first-line therapy in recruiting Italian Centers. Data about patient characteristics, safety and outcome were collected. Results: 170 pts have been treated from December 2020 to September 2023. The majority had clear-cell histology (83%). Sarcomatoid feature was present in 33%of available cases. About one half of patients (55%) had synchronous metastasis. 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%), bone and liver involvement in 66 and 29 patients (38.8% and 17.1%) respectively. Stratifying by IMDC criteria, 32 patients (18.8%) were at favorable-risk, 106 (62.4%) at intermediate-risk, and 32 (18.8%) at poor-risk. At time of analysis, treatment was ongoing in 49% of patients. Progression occurred in 45% of patients. Median PFS was 19.2 months (95% CI: 15-NR). With a median follow-up of 19.3 months (range 1.3-34.5), at 24-months and 36-months landmark analysis 62% (95% CI, 53-70) and 58% (95% CI, 47-69) of treated patients are still alive respectively. Disease control rate was achieved in 84.6% of patients: 4.3% reached a complete response, 52% had a partial response and 28.8% a stable disease. Primary progression was observed in 15.3% of patients. In the multivariate analysis, the prognostic significance of age >= 65 years, non-clear cell histology, IMDC score, and adverse events and gender interaction as predictors of worse OS were confirmed. Conclusion: This is the first available prospective study on first-line Pembrolizumab/Axitinib combination in real wor ld scenar io. Our findings support the effectiveness and safety of first-line this combination in mRCC and reveal that gender emerged as a prognostic factor in relation to the occurrence of adverse events.