The NAPOLEON study – a real-world, retrospective analysis of gemcitabine plus nab-paclitaxel and FOLFIRINOX in metastatic pancreatic cancer

There is an expanding evidence base supporting the first-line use of both FOLFIRINOX (fluorouracil + leucovorin + irinotecan + oxaliplatin) and gemcitabine plus nab-paclitaxel as adjuvant chemotherapy in patients with metastatic pancreatic cancer. Phase II and III clinical studies, including the PRODIGE 4/ACCORD 11 trial, demonstrated significant benefits in terms of progression free survival (PFS), overall survival (OS) and delay in the degradation of quality of life with FOLFIRINOX treatment, compared with gemcitabine alone.^1–3 These studies noted an increased toxicity with FOLFIRINOX versus gemcitabine.^2,3 Greater efficacy with gemcitabine plus nab-paclitaxel compared with gemcitabine alone has been shown in the MPACT trial,⁴ and in subsequent subanalyses the combination was associated with improved PFS, OS and response rate.^5,6  Gemcitabine plus nab-paclitaxel was less well tolerated than gemcitabine alone, with elevated incidence of neutropenia, fatigue, and neuropathy.^4–6

In routine practice, there remains uncertainty in the preferential selection of either approach, owing to the lack of head-to-head comparative data from any prospective clinical trials. Recently, retrospective studies have been carried out to provide evidence from the day-to-day clinical environment to guide treatment selection. These studies have broadly found similar OS and PFS times between the treatments, with the gemcitabine plus nab-paclitaxel approach demonstrating better tolerability in these trial populations.^7,8

 At the recent 21st European Society for Medical Oncology World Congress on Gastrointestinal Cancer (ESMO-GI), emerging data from the retrospective NAPOLEON study were shared, adding to the growing real-world evidence base intended to help inform treatment selection.⁹

The NAPOLEON study collected data from chemotherapy-naïve patients with metastatic pancreatic cancer from December 2013 to June 2018, in hospitals in Kyushu, Japan. Gemcitabine plus nab-paclitaxel was administered to 92 (43.6%) of study patients and FOLFIRINOX to 119 (56.4%); the median follow-up period was 14.9 months and 13.1 months in each group, respectively. Median OS was 10.2 months in the gemcitabine plus nab-paclitaxel cohort and 11.1 months in patients treated with FOLFIRINOX (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.72–1.34; p=0.91); median PFS was 5.5 months and 5.7 months (HR 1.05; 95% CI, 0.79–1.40; p=0.75), respectively. In practice, both treatments had similar overall response rates (p=0.72).

Real-world studies often use less stringently matched treatment groups, and in this study there were significant differences in some baseline characteristics. The gemcitabine plus nab-paclitaxel group contained older patients (68 years vs 61 years) and higher rates of peritoneal metastasis and ascites, but significantly lower rates of liver metastasis or family history of malignant tumours, than the FOLFIRINOX group.

In terms of tolerability, the FOLFIRINOX group had higher rates of grade 3/4 anorexia (20% versus 6%), diarrhoea (11% versus 0%) and nausea (11% versus 3%) than the gemcitabine plus nab-paclitaxel group. Comparatively, grade 3/4 fatigue (4% vs 0%) and peripheral sensory neuropathy (12% versus 3%) were more frequent in patients receiving gemcitabine plus nab-paclitaxel group that in those treated with FOLFIRINOX. Haematological adverse events and febrile neutropenia incidence were similar in both treatment approaches.

In agreement with other recent retrospective, real-world, treatment comparisons, the NAPOLEON study found similar efficacy with gemcitabine plus nab-paclitaxel and FOLFIRINOX in patients with metastatic pancreatic cancer. This study found both approaches to be relatively well tolerated, but with markedly different toxicity profiles.

Physicians should consider toxicity profiles, in conjunction with the patient’s health status, comorbidities and family history, alongside efficacy data, when selecting the preferred therapy for an individual in practice.

References

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2. Lambert A, Gavoille C and Conroy T. Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. Therap Adv Gastroenterol. 2017;10:631–
3. Thibodeau S and Voutsadakis IA. FOLFIRINOX chemotherapy in metastatic pancreatic cancer: a systematic review and meta-analysis of retrospective and Phase II studies. J Clin Med. 2018;7:7.
4. von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–
5. Tehfe M, Dowden S, Kennecke H, et al. nab-Paclitaxel plus gemcitabine versus gemcitabine in patients with metastatic pancreatic adenocarcinoma: Canadian subgroup analysis of the Phase 3 MPACT trial. Adv Ther. 2016;33:747–
6. Tabernero J, Kunzmann V, Scheithauer W, et al. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial. Onco Targets Ther. 2017;10:591–
7. Kim S, Signorovitch JE, Yang H, et al. Comparative effectiveness of nab-paclitaxel plus gemcitabine vs FOLFIRINOX in metastatic pancreatic cancer: a retrospective nationwide chart review in the united states. Adv Ther. 2018;35:1564–
8. Kang J, Hwang I, Yoo C, et al. nab-Paclitaxel plus gemcitabine versus FOLFIRINOX as the first-line chemotherapy for patients with metastatic pancreatic cancer: retrospective analysis. Invest New Drugs. 2018;36:732–
9. Nakazawa J, Otsuka T, Shimokawa M, et al. A multicenter retrospective study of gemcitabine plus nab-paclitaxel or FOLFIRINOX in metastatic pancreatic cancer: NAPOLEON study. P065; Abstract Book of ESMO 21st World Congress on Gastrointestinal Cancer July 2019, Barcelona, Spain. Ann Onc.