Efficacy and prognostic model development of immune checkpoint inhibitor rechallenge in recurrent or metastatic nasopharyngeal carcinoma: a real-world study.

[BACKGROUND] Immune checkpoint inhibitor (ICI) rechallenge in recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) is a promising therapeutic strategy. We aim to assess its treatment outcomes and build prognostic models for clinical practice.

[METHODS] R/M NPC patients who failed prior anti-PD-1 immunotherapy and received ICI rechallenge were enrolled. Clinical features were recorded, and univariate and multivariate analysis was conducted to evaluate prognostic factors. Prognostic models were developed and validated to predict progression-free survival (PFS) and overall survival (OS), respectively.

[RESULTS] A total of 243 patients were enrolled between January 2019 and December 2023. The objective response rate (ORR) and disease control rate (DCR) for the entire cohort were 24.3% and 75.7%, respectively. After a median follow-up of 10.5 months, the median PFS was 6.3 months, the median duration of response (DOR) was 9.8 months, and the median OS was 19.8 months. Multivariate Cox analysis identified that the latest efficacy of anti-PD-1 therapy (HR 0.587, 95%CI 0.357-0.963, p = 0.035), EBV DNA level (HR 1.743, 95%CI 1.252-2.426, p = 0.001), locoregional therapy (HR 0.467, 95%CI 0.268-0.812, p = 0.007), and rechallenge with anti-PD-1 inhibitor (HR 1.548, 95%CI 1.005-2.385, p = 0.047) were independent statistically prognostic factors for PFS. Additionally, age (HR 2.044, 95%CI 1.297-3.222, p = 0.002), bone metastatic (HR 1.642, 95%CI 1.055-2.555, p = 0.028), and EBV DNA level (HR 1.673, 95%CI 1.034-2.706, p = 0.036) were independent significantly associated with OS. Prognostic models were developed based on the risk factors. Stratification of patients by the prognostic scores from these models showed that the low-risk group patients had significantly improved PFS and OS compared to their high-risk counterparts.

[CONCLUSIONS] This study provided a comprehensive assessment of the efficacy and prognostic factors of ICI rechallenge in RM-NPC patients who failed prior anti-PD-1 immunotherapy, and developed a prognostic model which could identify candidates for ICI rechallenge. Further prospective trials are warranted to confirm and expand these findings.