Gemcitabine-Free Regimen Leads to Improved Survival in Metastatic Pancreatic Cancer

Pancreas

Results of the randomized phase II GERCOR trial concluded that patients with metastatic pancreatic cancer saw numerically better survival rates with a gemcitabine-free regimen when compared with a conventional gemcitabine regimen.

When compared with nab-paclitaxel (Abraxane), fluorouracil (5-FU)/leucovorin or gemcitabine led to objective responses in 35% of patients. The (5-FU)/leucovorin group exceeded the prespecified goal of a 4-month progression-free survival (PFS) rate of 50%.1 Additionally, patients randomized to the 5-FU/leucovorin regimen had a 12-month survival rate of 48% versus 41% for gemcitabine-containing therapy. The 18-month survival of the 5-FU/leucovorin group was more than twice that of the gemcitabine arm.

Tolerability was comparable between the 2 groups, Olivier Dubreuil, MD, a medical oncologist at Pitie Salpetriere Hospital in Paris, and colleagues reported at the 2017 Gastrointestinal Cancers Symposium in San Francisco.

“Results of the [gemcitabine] arm are concordant with those of the phase III MPACT study [that evaluated nab-paclitaxel/gemcitabine combination therapy],” the investigators concluded in a poster presentation. “The nab-paclitaxel/5-FU/leucovorin regimen deserves evaluation in a phase III trial.”

The MPACT trial showed that the addition of nab-paclitaxel to gemcitabine improved survival in metastatic pancreatic cancer as compared with gemcitabine alone.2 Translational data suggested that low expression of hENT1 predicts lack of response to gemcitabine,3 providing a rationale to evaluate regimens that do not include gemcitabine.

Dubreuil and colleagues reported findings from the randomized AFUGEM trial that compared the combination of nab-paclitaxel and simplified 5-FU/leucovorin (LV5FU2) with the nab-paclitaxel/gemcitabine regimen from the MPACT trial. Patients were randomized 2:1 to nab-paclitaxel/LV5FU2 or nab-paclitaxel/gemcitabine.

The primary endpoint of the trial was a targeted 4-month PFS of 50% in the experimental arm. If the trial met the endpoint, the nab-paclitaxel/LV5FU2 regimen was considered worthwhile for evaluation in a phase III trial.

Data analysis included 114 patients with previously untreated metastatic pancreatic cancer. The patients had a median age of 66 and an ECOG performance status of 0 to 2. About 37% of the patients had 2 or more metastatic sites, and 75% had liver metastases. About 13% of the patients had undergone surgical resection.

The LV5FU2 regimen had tolerability that was at least comparable to the gemcitabine regimen, including rates of grade 3/4 neutropenia (23.3% vs 23.7%), febrile neutropenia (8.2% vs 5.3%), anemia (5.5% vs 10.5%), thrombocytopenia (0% vs 15.8%), mucositis (9.6% vs 2.6%), diarrhea (12.3% vs 7.9%), fatigue (21.9% vs 21.1%), paresthesia (19.2% vs 10.5%), elevated ALT (4.1% vs 13.2%), and elevated AST (5.5% vs 13.2%).

Dubreuil and colleagues reported that about 80% of patients in both groups received the planned number of cycles of therapy at the specified dosages.

The objective response rate was 35.1% with LV5FU2 and 36% with the gemcitabine regimen. The 4-month PFS was 55.6% with LV5FU2 and 54% with gemcitabine. Median PFS was 5.9 months with LV5FU2 and 4.9 months with gemcitabine (HR, 0.79; 95% CI, 0.52-1.20).

With a median follow-up of 16.9 months, the LV5FU2 group had a median overall survival of 11.4 months compared with 9.2 months with the gemcitabine regimen. Overall survival rates favored the LV5FU2 group at 12 (48% vs 41%) and 18 months (34% vs 13%).

References

1. Dubreuil O, Bachet JB, Hammel P, et al. Nab-paclitaxel plus gemcitabine or plus simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic adenocarcinoma: A GERCOR randomized phase II study (AFUGEM). J Clin Oncol. 2017;35(suppl 4S; abstr 350).
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. Greenhalf W, Ghaneh P, Neoptolemos JP, et al; European Study Group for Pancreatic Cancer Investigators. Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial. J Natl Cancer Inst. 2014;106(1):djt347. doi:10.1093/jnci/gjt347.