The addition of the novel agent MM-398 to second-line 5-FU/leucovorin extended survival in patients with metastatic pancreatic cancer, according to an expanded analysis of the phase 3 NAPOLI-1 trial presented at the Gastrointestinal Cancer Symposium.
MM-398 (Merrimack Pharmaceuticals), which received fast track designation from the FDA based on its activity in this combination, is a nanotherapeutic derivative of the chemotherapy drug irinotecan. In this form, in which it is encapsulated in a lipid sphere, the agent can circulate longer than standard irinotecan.
In the open-label NAPOLI-1 trial, Li-Tzong Chen, MD, PhD, of director, investigator and attending physician at the National Institute of Cancer Research at National Health Research Institutes in Taiwan, and colleagues enrolled 417 patients from 76 sites in 14 countries. All patients had metastatic pancreatic cancer and had undergone prior treatment with gemcitabine-based therapy.
Researchers randomly assigned patients 1:1:1 to one of three arms. In Arm A, patients received MM-398 120 mg/m2 intravenously for 90 minutes every 3 weeks. In Arm B, patients received 5-FU at 2,000 mg/m2 for 24 hours plus racemic leucovorin 200 mg/m2 for 30 minutes every 4 weeks, followed by 2 weeks rest. In Arm C, patients received MM-398 80 mg/m2 intravenously for 90 minutes, followed by 5-FU 2,400 mg/m2 for 46 hours and racemic leucovorin 400 mg/m2 for 30 minutes every 2 weeks.
OS served as the primary endpoint.
Analysis of the per-protocol population — which included all patients who received at least 80% of the target dose in the first 6 weeks — showed those who received MM-398 plus 5-FU and leucovorin demonstrated median OS of 8.9 months (range, 6.4-10.5), whereas those who received 5-FU and leucovorin alone demonstrated median OS of 5.1 months (range 4.0-7.2 months). Researchers calculated an HR of 0.47 (95% CI, 0.29-0.77) in favor of the MM-398 combination.
Results showed MM-398 monotherapy did not confer a statistically significant OS advantage compared with 5-FU and leucovorin.
Subgroup analyses showed the addition of MM-398 to 5-FU and leucovorin was associated with improved OS among patients stratified by stage at diagnosis, number of previous therapies, time since last prior therapy and other pretreatment characteristics.
In the intent-to-treat population, which included all randomized patients, those assigned MM-398 plus 5-FU and leucovorin demonstrated longer median OS than those who received 5-FU and leucovorin alone (6.1 months vs. 4.2 months; HR=0.57; 95% CI, 0.41-0.8). Patients assigned the combination also demonstrated significant improvements in PFS (3.1 months vs. 1.5 months; P=.0001) and overall response rate (16% vs. 1%; P<.001).
A higher percentage of patients assigned the MM-398 regimen demonstrated a ≥50% reduction in CA 19-9 levels (36% vs. 12%; P=.0009).
The most frequent grade ≥3 adverse events reported in MM-398–treated patients in the NAPOLI-1 trial were neutropenia, fatigue, diarrhea and vomiting.
For more information:
Chen LT. Abstract #234. Presented at: 2015 Gastrointestinal Cancers Symposium; Jan. 15-17, 2015; San Francisco.
Disclosure: See the full study for a full list of financial disclosures.