Gemcitabine/nab-paclitaxel in first line treatment of advanced pancreatic cancer – head-to-head comparison with the mFOLFIRINOX regimen

Česká verzia

Authors: J. Tomášek
Authors place of work: Klinika komplexní onkologické péče LF MU a MOÚ, Brno
Published in the journal: Klin Onkol 2024; 38(5): 331-334
Category: Reviews
doi: https://doi.org/10.48095/ccko2024331

Summary

Background: Metastatic pancreatic ductal carcinoma (mPDAC) is one of the most lethal malignancies. The European Society for Medical Oncology (ESMO) guidelines recommend a gemcitabine doublet + nab-paclitaxel (Gem/Nab-P) or a modified FOLFIRINOX regimen (mFOLFIRINOX) as options for systemic chemotherapy. Gemcitabine monotherapy is an option for patients in a worse performance status (PS). Indirect comparisons of pivotal trials with Gem/Nab-P and mFOLFIRINOX vs. gemcitabine monotherapy (PRODIGE-4 and MPACT) indicated longer overall survival (OS) in patients treated with mFOLFIRINOX. However, it should be taken into account that the MPACT study with Gem/Nab-P included patients with an overall worse performance status. A direct comparison of these chemotherapy regimens was lacking. Indirect comparisons from real practice show their comparable effectiveness in terms of OS, progression-free survival and overall response rate. The safety profile is consistently different. The recently published phase II/III GENERATE trial, which directly compared Gem/Nab-P and mFOLFIRINOX in treatment-naïve mPDAC patients, demonstrated significantly longer OS in Gem/Nab-P-treated patients exceeding 17 months with a lower incidence of non-hematologic toxicity. The results sparked a lively discussion at the ESMO 2023 Congress. The comparison of Gem/Nab-P and mFOLFIRINOX was also addressed by prof. Prager in his presentation at the PragueONCO 2024 conference. Prager, who highlighted comparable efficacy of both regimens and better safety of Gem/Nab-P and demonstrated the benefit of Gem/Nab-P also in patients older than 70 years and those with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. It should also be taken into account that the choice of first line treatment determines the therapeutic options in the 2nd line. If the Gem/Nab-P regimen is used in the first line, pegylated liposomal irinotecan (nal-IRI) in combination with 5-fluorouracil and leucovorin (5-FU/LV) can be used in the second line. This regimen demonstrated prolongation of OS compared to 5-FU/LV in phase III study NAPOLI-1. In patients pretreated with the mFOLFIRINOX regimen, gemcitabine monotherapy or Gem/Nab-P can be used in the second line. Early examination of molecular predictive parameters will enable the identification of cases for which appropriate targeted therapy or immunotherapy is available.

Keywords:

Pancreatic cancer – FOLFIRINOX – gemcitabine/nab-paclitaxel – GENERATE study – nanoliposomal irinotecan

Zdroje

1. Conroy T, Desseigne F, Ychou M et al. Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364 (19): 1817–1825. doi: 10.1056/ NEJMoa1011923.

2. 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 (18): 1691–1703. doi: 10.1056/ NEJMoa1304369.

3. Conroy T, Pfeiffer P, Vilgrain V et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023; 34 (11): 987–1002.

4. Ohba A, Ozaka M, Ogawa G et al. Nab-paclitaxel plus gemcitabine versus modified FOLFIRINOX or S-IROX in metastatic or recurrent pancreatic cancer (JCOG1611, GENERATE): a multicenter, randomized, open-label, three-arm, phase 2/3 trial. ESMO Congress 2023, Abstract 1616O. [online]. Available from: https: //oncologypro.esmo.org/meeting-resources/esmo-congress/nab-paclitaxel-plus-gemcitabine-versus-modified-folfirinox-or-s-irox-in-metastatic-or-recurrent-pancreatic-cancer-jcog1611-generate-a-multicent.

5. ESMO daily reporter. Triplet therapy does not outperform doublet treatment first line in metastatic pancreatic cancer. [online]. Available from: https: //dailyreporter.esmo.org/esmo-congress-2023/gastrointestinal-cancers/triplet-therapy-does-not-outperform-doublet-treatment-first-line-in-metastatic-pancreatic-cancer.

6. Ozaka M, Nakachi K, Kobayashi S et al. A randomised phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel for locally advanced pancreatic cancer (JCOG1407). Eur J Cancer 2023; 181: 135–144. doi: 10.1016/j.ejca.2022.12.014.

7. 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 2022; 174: 102–112. doi: 10.1016/j.ejca.2022.06.042.

8. Marschner N, Hegewisch-Becker S, Reiser M et al. FOLFIRINOX or gemcitabine/nab-paclitaxel in advanced pancreatic adenocarcinoma: a novel validated prognostic score to facilitate treatment decision-making in real-world. Int J Cancer 2023; 152 (3): 458–469. doi: 10.1002/ijc.34271.

9. Pusceddu S, Ghidini M, Torchio M et al. Comparative effectiveness of gemcitabine plus nab-paclitaxel and FOLFIRINOX in the first-line setting of metastatic pancreatic cancer: a systematic review and meta-analysis. Cancers (Basel) 2019; 11 (4): 484. doi: 10.3390/cancers11040484.

10. Merza N, Farooqui SK, Dar SH et al. FOLFIRINOX vs. gemcitabine + nab-paclitaxel as the first-line treatment for pancreatic cancer: a systematic review and meta-analysis. World J Oncol 2023; 14 (5): 325–339. doi: 10.14740/ wjon1604.

11. Prager GW, Oehler L, Gerger A et al. Comparison of nab-paclitaxel plus gemcitabine in elderly versus younger patients with metastatic pancreatic cancer: analysis of a multicentre, prospective, non-interventional study. Eur J Cancer 2021; 143: 101–112. doi: 10.1016/ j.ejca.2020.11.003.

12. Macarulla T, Pazo-Cid R, Guillén-Ponce C et al. Phase I/II trial to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel in combination with gemcitabine in patients with pancreatic cancer and an ECOG performance status of 2. J Clin Oncol 2019; 37 (3): 230–238. doi: 10.1200/JCO.18.00089.

13. Wang-Gillam A, Hubner RA, Siveke JT et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors. Eur J Cancer 2019; 108: 78–87. doi: 10.1016/j.ejca.2018.12.007.