Nab-Paclitaxel With Leucovorin–Fluorouracil Shows Metastatic Pancreas Cancer Promise

Leucovorin and fluorouracil could offer an alternative to gemcitabine for use with nab-paclitaxel in metastatic pancreatic adenocarcinoma

medwireNews: Phase II results point to nab-paclitaxel plus a simplified regimen of leucovorin and fluorouracil as a possible combination for the first-line treatment of patients with metastatic pancreatic adenocarcinoma.

 

The regimen met the primary endpoint target of at least 50% of patients achieving 4 months of progression-free survival (PFS) and it had a "tolerable toxicity profile", the authors report in The Lancet Gastroenterology and Hepatology.

“Our results are encouraging and suggest that the efficacy of this regimen should be investigated in a phase 3 randomised trial, comparing it with the nab-paclitaxel plus gemcitabine regimen with a patient-centred outcome (ie, overall survival)”, they believe.

Jean-Baptiste Bachet, from Groupe hospitalier Pitié Salpêtrière in Paris, France, and co-workers explain that while nab-paclitaxel plus gemcitabine is currently the standard treatment for metastatic pancreatic adenocarcinoma, gemcitabine is thought to be inefficient in 50–60% of cases.

They designed the open-label, non-comparative AFUGEM GERCOR trial to assess activity and safety of the two nab-paclitaxel-based regimens in patients with at least one measurable lesion and an ECOG performance status of 2 or lower.

The patients were followed-up for a median of 13.1 months. At 4 months, PFS was achieved by 56% of the 72 patients given nab-paclitaxel with leucovorin plus fluorouracil and by 54% of the 39 patients given nab-paclitaxel plus gemcitabine.

Serious treatment-related adverse events occurred in a comparable 38% and 37% of the leucovorin plus fluorouracil and the gemcitabine groups, respectively, and there was one death in each arm, neither of which was considered treatment related.

Grade 3 or 4 side effects were less common with leucovorin plus fluorouracil than with gemcitabine (77 vs 87%) and the two regimens had different toxicity profiles, the researchers say.

Leucovorin plus fluorouracil was most commonly associated with grade 3–4 neutropenia without fever (23%), fatigue (22%), paraesthesia (19%), diarrhoea (12%) and mucositis (10%), whereas the most frequent grade 3–4 events with gemcitabine were neutropenia without fever (32%), fatigue (21%), thrombocytopenia (18%), anaemia and liver enzyme elevations (both 13%) and paraesthesia (11%).

Updated analysis after a median of 24.3 months gave a median PFS of 5.9 months for the leucovorin plus fluorouracil group versus 4.9 months for the gemcitabine group, with an exploratory hazard ratio of 0.79. The corresponding overall survival values were 11.4 versus 9.2 months and a hazard ratio of 0.61.

The researchers write that 61% and 21% of the patients given leucovorin plus fluorouracil received second- and third-line chemotherapy, respectively, as did 56% and 15% of the patients given gemcitabine.

Median overall survival from the beginning of second-line therapy was 4.6 and 6.5 months in the two groups, respectively, whereas for leucovorin plus fluorouracil-treated and gemcitabine-treated patients who were not given a second-line treatment, median overall survival was 2.1 and 1.7 months, respectively.

“These results suggest that simplified leucovorin and fluorouracil could be a better backbone companion than gemcitabine to develop new regimens in combination with nab-paclitaxel for pancreatic adenocarcinoma, and that this regimen deserves to be investigated further in clinical trials”, the authors conclude.

Reference

Bachet J-B, Hammel P, Desramé J, et al. Nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil as first-line therapy for metastatic pancreatic adenocarcinoma (AFUGEM GERCOR): a non-comparative, multicentre, open-label, randomised phase 2 trial. Lancet Gastroenterol Hepatol; Advance online publication 27 February 2017. DOI: http://dx.doi.org/10.1016/S2468-1253(17)30046-8

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