First-Line FOLFIRINOX May Have ‘Certain Advantages’ For Localised Pancreatic Cancer

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Patients with localised pancreatic ductal adenocarcinoma (PDAC) are more likely to achieve a partial response and become candidates for surgery after first-line fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) chemotherapy than with gemcitabine plus nab-paclitaxel (GA), research suggests.

However, the investigators did not find a significant difference in overall survival (OS) and several other clinical endpoints between the two chemotherapy regimens in their case series of 485 patients with treatment-naïve localised PDAC who attended The University of Texas MD Anderson Cancer Center in Houston, USA, between 2010 and 2017.

“Taken together, these data suggest that certain advantages may be associated with FOLFIRINOX in this setting”, write Matthew Katz and co-workers from the institution.

“FOLFIRINOX should thus be considered preferentially for patients without contraindications and who are anticipated to tolerate it”, they propose in JAMA Surgery, but recommend that “the choice between these regimens should also take into account their known toxicity profiles and each patient’s clinical status.”

On initial analysis, the 285 patients given FOLFIRINOX and the 200 patients given GA did not significantly differ in terms of serum cancer antigen (CA) 19-9 level response or radiographic reductions in tumour volume or tumour downstaging.

Further analysis indicated that FOLFIRINOX-treated patients were significantly less likely to have resectable disease than those given GA (32 vs 45%), yet they were also significantly younger (median age, 61 vs 71 years) and more likely to have an ECOG performance status of 2 or less (96 vs 82%).

Using propensity score-matched analysis to account for these discrepancies, the team found that 19% of 140 FOLFIRINOX-treated patients achieved a RECIST partial response to treatment versus 6% of 140 given GA, a significant difference.

The FOLFIRINOX cohort was also significantly more likely than the GA cohort to receive chemoradiation (50 vs 35%) and undergo pancreatectomy (27 vs 16%).

After a median follow-up of 33 months, patients who underwent pancreatectomy had a significantly longer median OS than those who did not (55 vs 17 months).

But there was no significant difference in OS among the FOLFIRINOX group overall compared with the GA cohort, at 21 versus 20 months. And OS was also comparable among the FOLFIRINOX patients who underwent resection versus the GA resection cohort (48 months vs not reached) and the corresponding treatment groups who did not receive surgery (18 vs 17 months).

Discussing the findings in a linked comment, Linda Ye and O Joe Hines, from the David Geffen School of Medicine at the University of California, Los Angeles, in the USA, suggest that “[s]ome caution should be used when interpreting these results” because of differences in radiotherapy use between the FOLFIRINOX and GA cohorts.

They also note that the absence of a significant decrease in serum CA 19-9 with either chemotherapy regimen contradicts earlier research indicating “this end point to be a strong preoperative estimator of survival.”

The commentators conclude: “Although this study shows a potential benefit of treatment associated with FOLFIRINOX, larger and prospective trials, such as S1505 (A Randomized Phase II Study of Perioperative mFOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel as Therapy for Resectable Pancreatic Adenocarcinoma), are required to inform management strategies and to improve patient outcomes.”

References

• Perri G, Prakash L, Qiao W, et al. Response and survival associated with first-line FOLFIRINOX vs gemcitabine and nab-paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma. JAMA Surg; Advance online publication 15 July 2020. doi:10.1001/jamasurg.2020.2286
• Ye L, Hines OJ. Should all patients with pancreatic cancer receive chemotherapy before surgery? JAMA Surg; Advance online publication 15 July 2020. doi:10.1001/jamasurg.2020.2302