First-Line FOLFIRINOX and Gemcitabine/Nab-Paclitaxel Show Comparable Survival in Advanced PDAC

Results from a phase 3 trial show similar results in regard to overall survival when patients with advanced pancreatic ductal adenocarcinoma were treated with either folinic acid, fluorouracil, irinotecan, oxaliplatin or gemcitabine/nab-paclitaxel in the first line.

Patients with pancreatic ductal adenocarcinoma (PDAC) treated with folinic acid, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX) or chemotherapy in the first line had similar outcomes in terms of overall survival (OS), although FOLFIRINOX was associated with a delay in progression, according to a phase 3 study published in the European Journal of Cancer.

The median OS was 11.3 months in patients who received gemcitabine/nab-paclitaxel vs 12.3 months in patients receiving FOLFIRINOX (HR, 1.15; 95% CI, 0.85-1.57; P = .37). Of these patients, 38% continued to second-line treatment which was associated with a longer median OS of 17.4 months vs 8.2 months for those who received first-line treatment alone (P <.001). The overall response rate in the gemcitabine group was 21.8% vs 20.5% in the FOLFIRINOX group.

A total of 1551 patients enrolled across 15 sites, 615 of whom had locally advanced or metastatic pancreatic cancer who received first-line palliative combination chemotherapy. Patients were selected for this retrospective analysis using data from the Australian PURPLE pancreatic cancer registry. Those excluded from the trial included those who received first-line palliative-intent radiotherapy, best supportive care alone, or who had less than 3 months of therapeutic follow-up data.

Those in the gemcitabine group were older with a median age of 67 years vs 59 years in the FOLFIRINOX group (P <.001), had a higher Charlson Comorbidity Index (P = .002), and a worse ECOG performance status (0 or 1: P = .01; 2: P = .04). Second-line chemotherapy was used in 37% of patients in the gemcitabine group vs 44% in the FOLFIRINOX group (P = .29).

Investigators did not find a significant association in the univariant analysis between the gemcitabine/nab-paclitaxel and FOLFIRINOX cohorts and progression (HR, 1.04; 95% CI, 0.78-1.38; P = .81) or OS (HR, 0.99; 95% CI, 0.64-1.53; P = .96).

Of those with locally advanced unresectable disease, 23 patients had first-line palliative FOLFIRINOX and 109 patients had gemcitabine/nab-paclitaxel. These patients within the subgroup had a median OS of 11.4 months vs 13.2 months with FOLFIRINOX and gemcitabine/nab-paclitaxel, respectively (HR, 1.20; 95% CI, 0.70-2.06; P = .96). Of note, both groups had a longer median OS than those in the first-line gemcitabine monotherapy group. Additionally, patients with de novo metastatic PDAC who received FOLFIRINOX and gemcitabine/nab-paclitaxel as first-line treatment had similar outcomes with a median OS of 12.1 months vs 9.0 months, respectively (HR, 0.93; 95% CI, 0.83-1.05; P = .24). In patients who received second-line chemotherapy, the median OS was 17.4 months (95% CI, 15.4-19.4) vs 8.2 months (95% CI, 7.3-9.1; P <.001) in patients who received less than 6 months of first-line therapy.

There was no significant difference in median OS between gemcitabine/nab-paclitaxel and second-line 5-flouracil (5FU) based regimens at 15.9 months (95% CI, 13.5-18.3) vs FOLFIRINOX and gemcitabine-based regimens at 17.3 months (95% CI, 12.8-21.8; P = .92). The median progression-free survival in those receiving second-line 5FU following first-line gemcitabine/nab-paclitaxel was 2.9 months (95% CI, 2.4-3.3) vs 5.2 months (95% CI, 2.5-8.0) in patients receiving FOLFIRINOX and second-line gemcitabine (P = .03).


Santucci J, Tacey M, Thomson B, et al. Impact of first-line FOLFIRINOX versus gemcitabine/nab-paclitaxel chemotherapy on survival in advanced pancreatic cancer: evidence from the prospective international multicentre PURPLE pancreatic cancer registry. Eur J Cancer. Published online August 18, 2022. doi:10.1016/j.ejca.2022.06.042