Oxaliplatin as Part of Sequential Chemotherapy Shows Promise in Metastatic Pancreatic Cancer

Patients newly diagnosed with metastatic pancreatic ductal adenocarcinoma (mPDAC) may benefit from a sequential chemotherapy approach that administers liposomal irinotecan followed by oxaliplatin, according to information presented by Christoph Benedikt Westphalen, MD, Munich, Germany, presented results from the phase 2 FOOTPATH trial (NCT03487016) at the European Society of Medical Oncology Congress in Berlin, Germany. The trial used 3 chemotherapy strategies for treatment-naïve patients with mPDAC. The first arm used the current standard of care, gemcitabine plus nab-paclitaxel (GNP); the second arm used liposomal irinotecan, folinic acid (leucovorin), and fluorouracil (5-FU), collectively known as the NAPOLI regimen; and the third arm followed the NAPOLI regimen sequentially but replaced irinotecan with oxaliplatin, resulting in the FOLFOX6 (folonic acid [leucovorin], 5-FU, and oxaliplatin) regimen.

The researchers' primary end point was to determine whether the sequential administration of irinotecan and oxaliplatin could maintain efficacy while simplifying treatment for mPDAC, as measured by patients' progression-free survival (PFS). The secondary end points included overall survival (OS), objective response rates, and safety.

What Was the Study's Design, and What Were the Results?

FOOTPATH-2 enrolled 274 patients across 48 German sites and then randomized the patients evenly between the three arms. Arm A received GNP (gemcitabine 1000 mg/m² plus nab-paclitaxel 125 mg/m²), Arm B received NAPOLI (liposomal irinotecan 80 mg/m², folinic acid 400 mg/m², and 5-FU 2400 mg/m²), and Arm C received NAPOLI followed by mFOLFOX6 (oxaliplatin 85 mg/m², folinic acid 400 mg/m², and 5-FU 2400 mg/m²). Nine patients ultimately stopped treatment across the 3 arms, leaving a full analysis set of 265 patients.

Patients treated with sequential NAPOLI followed by mFOLFOX6 achieved a statistically significant improvement in PFS compared with the standard of care (6.2 months vs 4.8 months; hazard ratio [HR], 0.84; 95% CI, 0.72–0.98; P = .0272). Those patients in Arm B who received NAPOLI monotherapy did not outperform the standard of care (median PFS of 3.1 months vs 4.8 months; HR, 1.22; P = .19).

Although the trial did not meet statistical significance for overall survival, a numerical trend favored the sequential approach. Median OS for Arm C was about 9.8 months compared with 8.5 months for Arm A (standard of care; HR, 0.89; P = .12). NAPOLI alone again failed to improve OS, with a median of 8.1 months. Safety outcomes across all three arms were consistent with previously reported toxicity profiles, and no new safety concerns emerged.

What Does This Mean for Pharmacists?

Further clinical trials are needed to prove whether these results can be replicated or improved and to further refine the standard of care and improve PFS and OS. Still, these phase 2 FOOTPATH results provide early evidence that a sequential approach may achieve comparable disease control with manageable safety.

Pharmacists can help patients and oncologists optimize transitions during sequential treatment, especially through proactive patient education and monitoring. Patients will likely wonder about sequential treatment compared to other treatment schedules, and anything that increases the odds of PFS and OS, even within a statistical standard deviation, can be a source of hope. By helping patients understand the current research landscape and emerging results, pharmacists can be a source of knowledge and comfort for patients with mPDAC.

REFERENCES

1. Westphalen CB, Gaska T, Reichert M, et al. Final results of FOOTPATH: A randomized, open-label phase II study of liposomal irinotecan plus 5-FU and folinic acid (NAPOLI) versus sequential NAPOLI and mFOLFOX6 versus gemcitabine/nab-paclitaxel in treatment-naïve metastatic pancreatic cancer (mPDAC). Presented at: ESMO Congress 2025; October 2025; Munich, Germany. Abstract 2221P.

2. ClinicalTrials.gov. First-line therapy in metastatic pancreatic ductal adenocarcinoma (FOOTPATH) [Internet]. Identifier: NCT03487016. [cited 2025 Oct 22]. Available from: https://clinicaltrials.gov/study/NCT03487016