SAN FRANCISCO — An updated analysis of the NAPOLI-1 trial has confirmed the survival benefit of liposomal irinotecan (Onivyde, Merrimack) in combination with fluorouracil (5-FU) and leucovorin in patients metastatic pancreatic cancer.
For patients who progressed after treatment with gemcitabine (Gemzar, Eli Lilly), the 12-month overall survival rate was substantially better with liposomal irinotecan than without (26% vs 16%), updated results show.
There was a similar improvement in 6-month survival estimates (53% vs 38%)
"This combination may be a new standard of care for this patient population," said lead author Andrea Wang-Gillam, MD, PhD, associate professor of medicine at Washington University School of Medicine in St. Louis, Missouri.
Dr Wang-Gillam presented the results here at the Gastrointestinal Cancers Symposium (GICS) 2016.
Liposomal irinotecan was recently approved by the US Food and Drug Administration (FDA) for this indication on the basis of earlier results from the NAPOLI-1 trial.
"The overall survival and progression-free survival benefit was maintained," Dr. Wang-Gillian told Medscape Medical News. "The FDA approved the drug in October 2015, so these data are reassuring, in that they confirm the efficacy." Toxicity was the same as in the early results, "even though there were more events," she reported.
"The combination of nanoliposomal irinotecan with 5-fluorouracil and leucovorin is appropriate for patients with metastatic pancreatic cancer that has progressed on first-line gemcitabine and nab-paclitaxel," said Smitha S. Krishnamurthi, MD, from the division of hematology and oncology at University Hospitals Case Medical Center & Case Western Reserve University in Cleveland. (In the phase 3 MPACT trial, the combination of nab-paclitaxel plus gemcitabine improved overall survival by about 2 months, compared with gemcitabine alone.)
"The treatment could also be offered to patients who have had disease progression on single-agent gemcitabine, if they are well enough for a combination chemotherapy regimen," Dr Krishnamurthi told Medscape Medical News.
Updated Results, Tie With Biomarker
The updated analysis was conducted after 378 events. Median overall survival was better with liposomal irinotecan than without (6.2 vs 4.2 months; unstratified hazard ratio [HR], 0.75; P = .0417).
At approximately 20 months, survival was similar in the two groups. "There were 19 patients, or about 16%, surviving beyond 20 months," Dr. Wang-Gillam reported. "And that is actually quite remarkable."
The NAPOLI-1 trial involved 417 patients with progressive metastatic pancreatic adenocarcinoma whose cancer progressed after treatment with gemcitabine.
Patients were randomized to one of three treatments. The liposomal irinotecan regimen consisted of liposomal irinotecan (80 mg/m² intravenously over 90 minutes) administered prior to fluorouracil (2400 mg/m² administered over 46 hours) and racemic leucovorin (400 mg/m² over 30 minutes) every 2 weeks. The monotherapy regimen consisted of liposomal irinotecan 120 mg/m² administered every 3 weeks. The control regimen consisted of 5-FU 2000 mg/m² plus racemic leucovorin 200 mg/m² administered weekly for 4 weeks, followed by 2 weeks of rest.
In the updated analysis, median overall survival was similar in the monotherapy and control groups (4.9 vs 4.2 months; HR, 1.08; P = .50).
In the liposomal irinotecan group and the monotherapy group, the most common adverse events of grade 3 or higher, occurring at an incidence of at least 2%, were neutropenia (20%), fatigue (14%), diarrhea (13%), vomiting (11%), and nausea (8%).
CA19-9 Correlates With Response
A related presentation from Dr. Wang-Gillam's team looked specifically at the correlation between the biomarker carbohydrate antigen 19-9 (CA19-9) and efficacy.
In patients with metastatic pancreatic cancer, it has been shown that there is a correlation between CA19-9 and response to therapy and overall survival, the researchers note.
In this analysis, 213 of the NAPOLI-1 trial participants had a baseline CA19-9 measurement.
CA19-9 response (≥50% decline from baseline) was better with the liposomal irinotecan regimen than with the control regimen (29% vs 9%; P = .0006). As CA19-9 levels increased, the benefit of liposomal irinotecan increased.
In those with the highest levels of CA19-9, median overall survival was better with the liposomal irinotecan regimen than with the control regimen (4.6 vs 1.9 months). Therefore, the CA19-9 serum level can provide information related to overall survival, the authors report.
Dr. Wang-Gillam reports relationships with Merrimack, Pfizer, Aduro Biotech, AstraZeneca, EMD Serono, Halozyme, Merrimack, Newlink Genetics, OncoMed, Pfizer, Precision Therapeutics, and Prometheus. Several coauthors report relationships with industry, as noted in the abstract. Dr. Krishnamurthi has disclosed no relevant financial relationships.
Gastrointestinal Cancers Symposium (GICS) 2016: Abstract 417. Presented January 21, 2016.
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Cite this: New Standard of Care in Metastatic Pancreatic Cancer? - Medscape - Feb 01, 2016.