Add-on nab-paclitaxel extends survival in metastatic pancreatic cancer

This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.

Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.

Dr. Philip A. Philip

Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.

In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.

The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.

If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.

What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.

Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.

Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.

Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.