Is Anktiva (nal-IRI) effective for treating pancreatic cancer in adults with advanced disease who have previously received gemcitabine-based therapy?

Is Anktiva Effective for Pancreatic Cancer?

No, Anktiva is not indicated for pancreatic cancer and should not be used for this disease. The term "Anktiva" does not refer to nanoliposomal irinotecan (nal-IRI), which is the FDA-approved agent for metastatic pancreatic adenocarcinoma after gemcitabine-based therapy failure.

Clarification on Terminology

The question appears to conflate "Anktiva" with nanoliposomal irinotecan (nal-IRI, brand name Onivyde). These are distinct medications:

• Nanoliposomal irinotecan (nal-IRI) is FDA-approved specifically for metastatic pancreatic cancer after gemcitabine-based therapy 1
• The evidence provided addresses nal-IRI, not "Anktiva"

Evidence for Nanoliposomal Irinotecan in Pancreatic Cancer

FDA-Approved Indication

Nanoliposomal irinotecan combined with 5-FU/leucovorin is recommended as a subsequent treatment option for patients with metastatic pancreatic adenocarcinoma who have good performance status and disease progression after gemcitabine-based therapy 1.

Efficacy Data from NAPOLI-1 Trial

The pivotal phase III NAPOLI-1 trial demonstrated:

• Median overall survival: 6.2 months vs 4.2 months with 5-FU/LV alone (HR 0.75, P=0.042) 1
• Median progression-free survival: 3.1 months vs 1.5 months (HR 0.56,95% CI 0.41-0.75, P<0.001) 1
• Survival benefit: Approximately 2-month improvement in median OS 2

Safety Profile

Grade 3-4 adverse events with nal-IRI + 5-FU/LV include:

• Neutropenia (27%) 1
• Fatigue (14%) 1
• Diarrhea (13%) 1
• Vomiting (11%) 1

Patient Selection Criteria

Optimal candidates for nal-IRI + 5-FU/LV:

• Good performance status (ECOG 0-1) 1
• Metastatic disease with progression after gemcitabine-based therapy 1
• No prior disease progression on conventional irinotecan 3

Critical Caveat: Prior Irinotecan Exposure

Patients with prior disease progression on conventional irinotecan have significantly worse outcomes:

• Median PFS: 2.2 months vs 4.8 months in irinotecan-naive patients (p=0.02) 3
• Median OS: 3.9 months vs 7.7 months (p=0.002) 3

However, patients who received prior irinotecan WITHOUT progression still benefit:

• Median PFS: 5.7 months (p=0.04) 3
• Median OS: 9.0 months (p=0.04) 3

Real-World Effectiveness

Post-approval studies confirm NAPOLI-1 findings:

• Median OS: 5.3-7.9 months 3, 4
• Median PFS: 2.9 months 3, 4
• Disease control rate: 38.8% 4
• Objective response rate: 10.4% 4

Sequential Therapy Strategy

Sequential use of nab-paclitaxel + gemcitabine followed by nal-IRI + 5-FU/LV demonstrates encouraging outcomes:

• Median OS: 23.0 months with this sequential approach 3

Dose Modifications

Dose reductions do not compromise efficacy and may improve tolerability:

• Patients with ≥1 dose reduction experienced longer PFS (5.4 vs 2.6 months, p=0.035) 3
• Most common reasons for dose reduction: fatigue (42%) and diarrhea (37%) 3
• Median dose intensity in real-world practice: 40.4 mg/m² 4

Predictors of Poor Outcomes

Avoid nal-IRI + 5-FU/LV or use with extreme caution in patients with:

• Elevated total bilirubin (HR 4.31, p=0.024) 4
• Carcinomatosis (HR 3.75, p=0.006) 4
• Prior progression on conventional irinotecan (HR 4.86, p=0.004) 4
• TP53 mutations (associated with shorter PFS) 3

Alternative Second-Line Options

For patients previously treated with gemcitabine-based therapy, other acceptable options include 1:

• 5-FU/leucovorin with oxaliplatin (OFF regimen): Median OS 5.9 months (HR 0.66, P=0.01) 1
• Modified FOLFIRI: Median OS 6.6 months 1
• Modified FOLFOX: Median OS 6.7 months, though PANCREOX trial showed potential detriment with increased toxicity 1