2016 GI Symposium: Irinotecan Liposome Injection in Metastatic Pancreatic Cancer: Updated Results of the Phase III NAPOLI-1 Study
Merrimack Pharmaceuticals, Inc, announced that an updated overall survival analysis of the phase III NAPOLI-1 study of irinotecan liposome injection (Onivyde) in combination with fluorouracil (5-FU) and leucovorin achieved a substantial improvement in 12-month overall survival compared to 5-FU and leucovorin alone in patients with metastatic pancreatic adenocarcinoma who had received prior gemcitabine therapy. These updated data were presented in two abstracts at the 2016 Gastrointestinal Cancers Symposium in San Francisco.
Analysis of the updated data supports the robustness of the overall survival benefit of the irinotecan liposome injection combination therapy observed in the primary analysis of the NAPOLI-1 trial. Updated findings showed one in four patients treated with irinotecan liposome injection survived a milestone of 1 year or more: 12-month overall survival estimates of 26% (95% confidence interval [CI] = 18%–35%) for irinotecan liposome injection in combination with 5-FU and leucovorin, a 63% improvement when compared to 16% (95% CI = 10%–24%) for 5-FU and leucovorin alone. No new safety or tolerability concerns were note in the updated analysis.
“Pancreatic cancer is a devastating disease with dismal survival,” said Andrea Wang-Gillam, MD, PhD, lead author of the NAPOLI-1 article and Associate Professor of Medicine, Clinical Director of GI Oncology Program, Division of Oncology, at Washington University School of Medicine, St. Louis. “These updated findings reinforce the overall survival benefit of irinotecan liposome injection in treating patients with metastatic pancreatic adenocarcinoma who have had disease progression after gemcitabine-based therapy. With a significant improvement in the 12-month overall survival rate and a well-defined safety and tolerability profile, the irinotecan liposome injection combination regimen is well positioned to become the standard of care in the post-gemcitabine setting. This new therapy offers hope for extended life expectancy in a patient population with limited options.”
Updated Overall Survival Analysis of NAPOLI-1
In this analysis of updated data from the NAPOLI-1 study presented by Wang-Gillam et al (Abstract 417), the previously described overall survival and progression-free survival benefits were maintained for the irinotecan liposome injection in combination with 5-FU and leucovorin arm compared with 5-FU and leucovorin alone. This data analysis presents updated estimates of overall survival based on 378 events and includes data from all patients randomized across the three arms of the study.
Twelve-month survival estimates for irinotecan liposome injection in combination with 5-FU and leucovorin were 26% (95% CI = 18%–35%) compared to 16% (95% CI = 10%–24%) for 5-FU and leucovorin alone. Six-month survival estimates were 53% (95% CI = 44%–62%) for the irinotecan liposome injection combination regimen vs 38% (95% CI = 29%–47%) for 5-FU and leucovorin.
No new safety or tolerability concerns were noted in the updated data analysis. The most common grade 3+ adverse events occurring at a ≥ 2% incidence in the irinotecan liposome injection-containing arms were neutropenia, diarrhea, vomiting, and fatigue.
Effect of Baseline CA19-9 Level on Overall Survival in NAPOLI-1
Carbohydrate antigen 19-9 (CA19-9) has been shown to correlate with response to therapy and overall survival in patients with metastatic pancreatic cancer. In this updated analysis of NAPOLI-1 data presented by Chen et al (Abstract 425), patients with a recorded baseline CA19-9 measurement were divided into quartiles to evaluate the treatment effect pattern of CA19-9 levels with irinotecan liposome injection in combination with 5-FU and leucovorin or 5-FU and leucovorin alone. A total of 213 patients treated with the irinotecan liposome injection combination regimen or 5-FU and leucovorin alone had a baseline CA19-9 measurement and were included in this analysis.
Results show the observed overall survival and progression free survival benefits for the irinotecan liposome injection combination regimen compared to 5-FU and leucovorin alone were greatest among patients with the highest baseline CA19-9 levels. These results suggest that baseline CA19-9 levels are associated with the treatment effect observed for the irinotecan liposome injection combination regimen in patients with metastatic pancreatic cancer.
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