Real-World Data Validation of NAPOLI-1 Nomogram for the Prediction of Overall Survival in Metastatic Pancreatic Cancer

SIMPLE SUMMARY: The nomogram derived from the pivotal phase III NAPOLI-1 study could predict the overall survival in gemcitabine-refractory metastatic pancreatic cancer treated with liposomal irinotecan plus fluorouracil and leucovorin. However, the NAPOLI-1 nomogram has not been validated in a real-world setting and therefore the applicability of the NAPOLI-1 nomogram in daily practice remains unknown. In the current study, we validated the NAPOLI-1 nomogram in a multicenter real-world cohort and confirmed that the NAPOLI-1 nomogram could predict the prognosis of gemcitabine-refractory metastatic pancreatic cancer in daily practice and may help clinical decision making. We further found that the relative dose intensity at 6 weeks was an independent prognostic factor beyond the NAPOLI-1 nomogram, which highlighted the importance of optimal dose delivery regardless of the baseline condition. ABSTRACT: Background: The nomogram derived from the pivotal phase III NAPOLI-1 study demonstrated a significant ability to predict median overall survival (OS) in gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (PDAC) treated with liposomal irinotecan plus fluorouracil and leucovorin (nal-IRI+5-FU/LV). However, the NAPOLI-1 nomogram has not been validated in a real-world setting and therefore the applicability of the NAPOLI-1 nomogram in daily practice remains unknown. This study aims to evaluate the NAPOLI-1 nomogram in a multicenter real-world cohort. Methods: The NAPOLI-1 nomogram was applied to a previously established cohort of metastatic PDAC patients treated with nal-IRI+5-FU/LV in nine participating centers in Taiwan. Patients were divided into three risk groups according to the NAPOLI-1 nomogram. The survival impact of relative dose intensity at 6 weeks (RDI at 6 weeks) in different risk groups was also investigated. Results: Of the 473 included patients, the median OSs of patients classified as low (n = 156), medium (n = 186), and high (n = 131) risk were 10.9, 6.3, and 4.3 months, respectively (p < 0.0001). The survival impact of RDI at 6 weeks remained significant after stratification by risk groups, adjustment with Cox regression, inverse probability weighting, or propensity score matching. Conclusions: Our results support the usefulness of the NAPOLI-1 nomogram for risk stratification in gemcitabine-refractory metastatic PDAC treated with nal-IRI+5-FU/LV in daily practice. We further showed that the RDI at 6 weeks is an independent prognostic factor beyond the NAPOLI-1 nomogram.