But overall survival rates similar between two treatment groups

First-line chemotherapy with the FOLFIRINOX regimen (fluorouracil, leucovorin, irinotecan and oxaliplatin) led to higher rates of radiographic partial response than the combination of gemcitabine plus nab-paclitaxel (GA) in patients with localized pancreatic ductal adenocarcinoma (PDAC) but overall survival (OS) rates were very similar between the 2 treatment groups, a single-center experience has shown.

In a consecutive, unselected series of 485 patients who presented during a 7-year period for the treatment of localized PDAC, a partial response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was achieved in 19% of propensity-matched patients treated with FOLFIRINOX compared with 6% of those treated with GA (P=0.001), Matthew Katz, MD, The University of Texas MD Anderson Cancer Center in Houston and colleagues reported in JAMA Surgery.

However, many metrics of treatment response did not differ between the 2 groups, including primary tumor volume, tumor downstaging or serum cancer antigen 19-9 levels.

Moreover, median OS at 21 months (95% CI, 18-24 months) for FOLFIRINOX patients versus 20 months (95% CI, 17-25 months) for GA patients was very similar, investigators noted.

“FOLFIRINOX and GA are the favored first-line chemotherapeutic regimens for patients with advanced PDAC…[but] these 2 regimens have been increasingly used as the first-line treatment for patients with localized disease, typically with ’preoperative’ intent,” Katz and colleagues observed.

“FOLFIRINOX should thus be considered preferentially for patients without contraindications and who are anticipated to tolerate it [although] the choice between these regimens should also take into account their known toxicity profiles and each patient’s clinical status,” they cautioned.

All patients included in the analysis received at least 3 cycles of first-line chemotherapy with either FOLFIRINOX or GA.

Fifty-nine percent of the group received FOLFIRINOX while 41% received GA as first-line chemotherapy.

Patients treated with FOLFIRINOX were generally younger at a median age of 61 years at diagnosis (range, 30-81 years) compared with a median age of 71 years at diagnosis (range, 36-89 years) for those treated with GA (P=0.001), study authors note.

FOLFIRINOX patients also had a more favorable performance status than their GA counterparts, some 96% of whom had an Eastern Cooperative Oncology Group (ECOG) score of 2 or lower compared with 82% of GA patients (P=0.001).

On the other hand, FOLFIRINOX patients had more invasive primary tumors with only 32% of their tumors being amenable to resection compared with 45% of GA patients whose tumors were similarly resectable, as investigators explained (P=0.01).

Thus, investigators did a propensity score matching analysis to control for potential selection bias in the delivery of either first-line protocol.

And in this matched cohort, “[n]o differences were observed in the median change in tumor volume, the rate of local tumor downstaging or CA 19-9 levels,” as the authors noted.

In the overall cohort, 44% of the group subsequently went on to receive radiation or chemoradiation after first-line chemotherapy while 22% ultimately underwent pancreatectomy following radiation or chemoradiation.

However, more FOLFIRINOX patients actually received radiation or chemoradiation at 50% than those treated with GA at 34% (P=0.001), as the authors pointed out.

Similarly, more FOLFIRINOX patients underwent pancreatectomy at 27% compared with 16% of GA patients (P=0.01).

This was also true in the propensity-matched cohort among whom 53% of FOLFIRINOX patients received radiation or chemoradiation compared with 34% of their GA counterparts (P=0.001).

Matched FOLFIRINOX patients were also more likely to undergo pancreatectomy at 29% compared with 18% for GA patients (P=0.02), researchers added.

Overall, median OS of patients who underwent pancreatectomy was longer at 55 months (95% CI, 38-not reached compared with a median of 17 months (95% CI, 16-18 months) for patients who did not undergo pancreatectomy (P<0.001).

In contrast, median OS among patients who underwent resection versus those who did not did not differed significantly between FOLFIRINOX and GA patients.

Limitations of the study include the fact that investigators did not evaluate patient-reported outcomes or quality of life.

Nor did they evaluate adverse events (AEs) associated with either regimen.

“Consideration of these parameters is clearly important in selecting between potential regimens,” as they underscored.

In an invited commentary , Linda Ye, MD, and Joe Hines, MD, both from the David Geffen School of Medicine at the University of California in Los Angeles, noted that some caution is needed when interpreting results because rates of radiation use were higher in the FOLFIRINOX group compared with the GA group.

“[S]ubsequent therapies patients received were variable and not accounted for in this retrospective study,” the editorialists added.

As Ye and Hines observed, there is as yet no consensus on the optimal sequence of surgery and chemotherapy in patients with resectable PDAC.

Nevertheless, at this point in time, “neoadjuvant chemotherapy appears to be most beneficial for those with borderline resectable or locally advanced disease,” they observed.

“Although this study shows a potential benefit of treatment associated with FOLFIRINOX, larger and prospective trials…are required to inform management strategies and to improve patient outcomes [in this patient population],” they concluded.

  1. First-line FOLFIRINOX led to higher rates of radiographic partial response than gemcitabine/nab-paclitaxel in localized pancreatic ductal adenocarcinoma, but higher radiographic partial responses did not affect overall survival between the two treatment groups.

  2. Be aware that the editorialists note that some caution is needed when interpreting results because rates of radiation use were higher in the FOLFIRINOX group compared with the GA group.

Pam Harrison, Contributing Writer, BreakingMED™

Katz had no conflicts of interest to declare.

The editorialists had no disclosures to make.

Cat ID: 935

Topic ID: 78,935,730,935,192