Pancreatic Cancer: Combination Chemotherapy Increases Survival

Andrea Wang-GillamMD, PhD Assistant Professor, Department of Medicine Oncology Division, Medical Oncology Section Washington University School of Medicine in St. Interview with:
Andrea Wang-GillamMD, PhD
Assistant Professor, Department of Medicine
Oncology Division, Medical Oncology Section
Washington University School of Medicine in St. Louis

Medical Research: What are the main findings of the study?

Dr. Wang-Gillam: This is a global randomized phase III trial of MM398 plus 5FU/LV vs. MM398 vs. 5FU/LV in patients with metastatic pancreatic cancer who had received prior gemcitabine-based therapy. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), response rate (RR), biochemical response and safety. The trial achieved its primary endpoint. The median overall survival was statistically longer with the combination of MM398 plus 5FU/LV compared with 5FU/LV alone (6.1 months vs 4.2 months; HR of 0.67; p=0.0122). A superior progression-free survival was also seen in the MM398 plus 5FU/LV group compared with the 5FU/LV alone group (3.1 months vs 1.5 months; HR of 0.56; p=0.0001). A higher response rate was observed in the combination regimen compared with the 5FU/LV group (16% vs 1%). There were no differences in overall survival or PFS between the MM 398 monotherapy and 5FU/LV groups.

Medical Research: Were any of the findings unexpected?

Dr. Wang-Gillam: Some unexpected findings appeared in the MM398 monotherapy arm.

First, in terms of efficacy, although MM398 monotherapy resulted in a higher RR and biochemical response compared with 5FU/LV, there was no difference in OS and PFS between MM 398 monotherapy and 5FU/LV treatment.

Second, regarding toxicity, the study reported a higher incidence of grade 3 or above adverse events in the GI tract such as diarrhea, vomiting and hypokalemia in the MM398 monotherapy group compared with the MM398 plus 5FU/LV group.

Medical Research: What should clinicians and patients take away from your report?

Dr. Wang-Gillam: There are a couple of important take home messages from this study.

  • First, the study has met its primary endpoint demonstrating that the combination of MM398 plus 5FU/LV resulted in a superior overall survival compared with 5FU/LV alone.
  • The combination could be another treatment option for metastatic pancreatic cancer patients who have previously received gemcitabine-based regimens. Second, the toxicities of the combination of MM398 plus 5FU/LV were acceptable and manageable.
  • Third, the study accrued 417 patients globally in less than 2 years, reflecting a desperate need for novel therapy in this patient population.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Wang-Gillam: MM398 is a novel delivery system for irinotecan. Because of the delivery system, MM398 can linger in circulation longer compared with the conventional irinotecan. Furthermore, this nanoliposomal delivery system allows a higher uptake of the drug at the tumor site and possible subsequent local conversion to its active metabolite SN-38. In light of these favourable features, I anticipate MM398 will be studied for the treatment of many different kinds of tumors, especially those for which conventional irinotecan has already demonstrated its clinical efficacy. As a GI oncologist, I would like see large clinical studies using regimens containing MM398 in several GI cancers including colorectal cancer and gastric cancer.

Last but not least, in light of the efficacy of FOLFIRINOX, I personally would advocate for a study investigating MM398 combined with 5FU/LV and oxaliplatin in the front-line setting for locally advanced or metastatic pancreatic cancer.

Citation: Abstract

MM-398 Added to Standard Treatment Shows Survival Benefit in Mets Pancreatic Cancer
Published: June 25, 2014. By European Society for Medical Oncology