Dr. Nagourney's Blog

Choosing Therapy For Stage 4 Pancreatic Cancer: What Are The Criteria?

By Robert A. Nagourney, MD

Pancreatic cancer afflicts 53,000 patients each year in the U.S. and has overtaken breast cancer as the third leading cause of cancer death in the United States.

While newer chemotherapy combinations have had some impact, the gains have generally been modest and obtained at the cost of significant toxicity.

How Do Oncologists Choose Metastatic Pancreatic Cancer Treatments?

A recent analysis examined patterns of chemotherapy use in the United States and came to some interesting conclusions regarding how medical oncologists choose treatments for their patients.

The study analyzed 4,011 patients with metastatic pancreatic carcinoma (stage 4 pancreatic cancer) treated at both academic centers and private practices and compared patterns of drug use from January 2005 to December 2015.

Analyses included the choice of treatment regimen and the frequency with which second and third line therapies were administered.

In 2017, available therapies for advanced pancreatic cancer include single agent Gemcitabine, Gemcitabine plus Capecitabine, Gemcitabine plus Erlotinib (Tarceva®), Oxaliplatin plus Gemcitabine and the widely used FOLFIRINOX and Gemcitabine plus nab-Paclitaxel regimens.

Results of the Survey

The findings are of interest.

First, the use of single agent Gemcitabine declined rapidly over the last ten years from over 70% to only 16%.

Since 2010, FOLFIRINOX use has risen to 29% and Gemcitabine plus nab-Paclitaxel to 38% of patients. Gemcitabine plus Erlotinib (Tarceva®) and Gemcitabine plus Oxaliplatin have each remained low, in the range of 10%.

What was most striking was the analysis of factors associated with physician choice of drug regimen. While one might hope that objective measures and scientific data drive therapy selection, the findings painted a rather different picture.

It appears that the use of FOLFIRINOX is predicted by younger age, male gender and geographic location with patients who reside in the Western United States having a higher likelihood of receiving this drug regimen in the first-line.

The independent predictors for the choice of Gemcitabine plus nab-Paclitaxel are the receipt of care in a community-based practice and treatment in a center with a lower volume of Stage 4 pancreatic cancer patients.

Durations of therapy were similar for FOLFIRINOX and Gemcitabine plus nab-Paclitaxel and longer than single agent Gemcitabine but these differences were not very large. Second and third line therapy has increased demonstrably over the ten-year period, with patients receiving care at academic institutions having the highest likelihood of receiving third line chemotherapy.

Some Points to Consider

The analysis raises a number of interesting points that warrant further consideration.

The first is that these treatment regimens do not have equal response rates.  Indeed, FOLFIRINOX has an almost 35% higher objective response rate over nab-Paclitaxel plus Gemcitabine (31% vs. 23%).

The second is that these combinations are not of equivalent toxicity or expense to administer.

The third and most disturbing is the fact that no objective measure is applied to make critical, life and death decisions regarding what combination to use in this seriously ill population.

Were I a cancer patient, I would certainly hope the choice of my treatment was predicated upon more than my age, gender and geographic location.

It is the last point that is of most concern.

Is There a Better Way to Choose Treatments?

Laboratory models such as the EVA-PCD assay can select amongst treatment options.

It is not difficult to imagine that for any given patient, one class of drugs may be more active than another. Clearly nab-Paclitaxel plus Gemcitabine work differently from FOLFIRINOX.

Are we to imagine that all patients have equivalent treatment response expectations? And that all patients will have equivalent toxicities?

Is it too much to expect medical oncologists to make the effort to identify the right treatment for each patient, in a disease that kills 41,000 of the 53,000 patients diagnosed each year?

It seems it is time for patients with Stage 4 pancreatic cancer to demand more of their physicians.

As always, I appreciate your thoughts and comments.

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