The last few years have seen the development of two combination chemotherapy regimens for the initial treatment of metastatic pancreatic cancer. FOLFIRINOX demonstrated superior survival compared to the historical standard of gemcitabine monotherapy.1

Subsequently, the combination of gemcitabine with nab-paclitaxel improved survival compared with gemcitabine monotherapy.2

Thus, two combination chemotherapy regimens are available and appropriate for initial therapy for patients with metastatic pancreatic cancer with good performance status. What to do beyond first-line therapy remains a clinical challenge.

While clinicians often offer the “other” regimen to patients with preserved performance status in second-line, limited data exist to support this approach. Thus, development of new agents in refractory disease remains a key unmet need in pancreatic cancer.

Against this backdrop, MM-398 was developed in refractory pancreatic cancer. MM-398 (previously PEP02) is a liposomal encapsulated formulation of irinotecan. This liposomal formulation can result in improved pharmacokinetics and tumoral drug delivery of irinotecan and SN-38, its active metabolite.3

Steven J. Cohen, MD
Steven J. Cohen, MD

Ko and colleagues conducted a single arm phase 2 study of MM-398 in patients with gemcitabine-refractory metastatic pancreatic cancer.4 Forty patients with good PS (Karnofsky ≥70) were treated with MM-398, 120 mg/m2 every 3 weeks. The primary endpoint was 3-month survival.

RELATED: Gemcitabine Plus FOLFIRI May Be Safe and Effective as First-Line Treatment of Metastatic Pancreatic Cancer

The most common grade 3/4 toxicity was neutropenia (30%), with fatigue, diarrhea, and abdominal pain also noted. The response rate was 7.5% with approximately 43% of patients achieving stable disease as best response. Median PFS and OS were 2.4 months and 5.2 months, respectively. The study met its primary endpoint, with 75% of patients surviving at least 3 months.