Shedding More Light On Neoadjuvant Treatment

The standard of care for resectable pancreatic cancer is surgery followed by adjuvant chemotherapy.

But about half of patients who undergo surgery are not able to receive adjuvant chemotherapeutic treatment due to post-operative issues. The overarching thought regarding neoadjuvant treatment is that in theory it could improve the chances of negative surgical margins, provide early treatment of systemic disease, show how well a patient may respond to chemotherapy, and potentially shrink a tumor, making surgery somewhat easier.

The two chemotherapy regimens most commonly used in the neoadjuvant setting are FOLFIRINOX or gemcitabine plus nab-paclitaxel (Abraxane). It is generally believed that FOLFIRINOX is somehow more effective. A new study in JAMA Surgery shows tumors may respond more often to FOLFIRINOX when it is used as an upfront treatment among patients with localized pancreas cancer. But the study also shows median overall survival is pretty much the same between regimens.

“We weren’t particularly surprised by these results,” says lead investigator Matthew Katz, M.D., Chief of Pancreatic Surgery and Associate Professor in the Department of Surgical Oncology at The University of Texas MD Anderson Cancer Center (Houston, Texas). “Generally I think it’s believed that FOLFIRINOX is the more effective regimen for neoadjuvant chemotherapy but it hasn’t been compared head-to-head with gemcitabine plus nab-paclitaxel in any clinical setting.

“The point of our study was to evaluate both radiographic response and survival. Our data show that FOLFIRINOX was associated with higher rates of radiographic response, and patients underwent pancreatectomy more frequently after treatment with FOLFIRINOX than gemcitabine plus nab-paclitaxel. But the overall survival for both cohorts was absolutely similar.”

About the Study

In the retrospective study, Katz and colleagues looked at 485 consecutive patients diagnosed between January 2010 and December 2017 at MD Anderson who received at least three cycles of first-line FOLFIRINOX or gemcitabine plus nab-paclitaxel. The median follow-up was 33 months. In all, 37 percent of patients had tumors that were considered resectable, 28 percent had borderline resectable disease, and 35 percent had locally advanced pancreatic tumors.

In their analysis, the researchers used a statistical technique called propensity scoring. It is often used when scientists look at retrospective data. The so-called scoring weighs two nonequivalent groups on observed characteristics in a way that helps eliminate any bias. That’s done by matching study participants in comparison groups on propensity scores, among other techniques. This kind of statistical analysis provides a more uniform distribution of patient characteristics in a final data analysis.

According to study results:

• In a propensity score-matched analysis that included 140 patients in each group, patients in the FOLFIRINOX group were more likely to receive immediate treatment with chemoradiation.
• Those patients were also more likely to undergo pancreatectomy.
• There were no significant differences in tumor volume reduction, tumor downstaging, or change in CA19-9. (CA19-9 is a protein. High levels of CA 19–9 can be a sign of certain cancers, including pancreatic cancer.)
• The FOLFIRINOX group had a higher radiographic response rate of 19 percent vs. 6 percent.
• Despite the increase in the rate of resection, median overall survival among all patients was not significantly different between the two groups. Median overall survival was 21 months with FOLFIRINOX vs. 20 months with gemcitabine plus nab-paclitaxel, including a median overall survival of 48 months vs not reached in individuals undergoing resection.

“Our survival results were concordant to those reported in the SWOG S1505 trial,” which were presented at the ASCO20 Virtual Scientific Program, Katz says. In that trial, results showed that modified FOLFIRINOX was not better than a regimen of gemcitabine/nab-paclitaxel. Neither led to an improvement in two-year survival over historical rates.

Much of the conviction behind FOLFIRINOX as the preferred choice in the neoadjuvant setting is that it’s such a superstar in the adjuvant setting. For example, modified FOLFIRINOX provided patients a median 20-month overall survival improvement compared to gemcitabine, according to results of the PRODIGE 24 Trial. The improvement of median overall survival from 35 months with gemcitabine to slightly more than 54 months with FOLFIRINOX represents a 36 percent reduction in the risk for death among patients assigned to the FOLFIRINOX regimen, according to the study which was published in the New England Journal of Medicine.

One issue with FOLFIRINOX is that it’s a tough regimen with some potentially serious toxicities. “What I take away from our study and the SWOG S1505 study is that if a patient comes in with localized cancer and the patient is robust and wants more aggressive chemotherapy, consider treating with FOLFIRINOX,” says Katz. “But if a patient is not anticipated to tolerate treatment with FOLFIRINOX, treatment with that regimen should not be pursued in a misguided effort to treat ‘more aggressively.’

“The data suggest a reasonable backbone that includes either regimen is appropriate. While it is entirely reasonable to treat patients with FOLFIRINOX if they are expected to tolerate it well, patients unlikely to tolerate it should be treated with gemcitabine and Abraxane.”