Improving Survival in Metastatic Pancreatic Cancer
Patients with metastatic pancreatic cancer saw better survival rates with a gemcitabine-free regimen when compared to a conventional gemcitabine regimen, according to the randomized phase 2 GERCOR trial.
When compared with Abraxane (nab-paclitaxel), fluorouracil (5-FU)/leucovorin or gemcitabine led to objective responses in 35 percent of patients. The (5-FU)/leucovorin group exceeded the pre-specified goal of a four-month progression-free survival (PFS) rate of 50 percent. Additionally, patients randomized to the 5-FU/leucovorin regimen had a 12-month survival rate of 48 percent versus 41 percent 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 two groups, Olivier Dubreuil, M.D., 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 3 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 3 trial.”
The MPACT trial showed that the addition of nab-paclitaxel to gemcitabine improved survival in metastatic pancreatic cancer as compared with gemcitabine alone. Translational data suggested that low expression of hENT1 predicts lack of response to gemcitabine, 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 in a 2 to 1 ratio to nab-paclitaxel/LV5FU2 or nab-paclitaxel/gemcitabine.
The primary endpoint of the trial was a targeted four-month PFS of 50 percent in the experimental arm. If the trial met the endpoint, the nab-paclitaxel/LV5FU2 regimen was considered worthwhile for evaluation in a phase 3 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 percent of the patients had two or more metastatic sites, and 75 percent had liver metastases. About 13 percent 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 percent vs 23.7 percent), febrile neutropenia (8.2 percent vs 5.3 percent), anemia (5.5 percent vs 10.5 percent), thrombocytopenia (0 percent vs 15.8 percent), mucositis (9.6 percent vs 2.6 percent), diarrhea (12.3 percent vs 7.9 percent), fatigue (21.9 percent vs 21.1 percent), paresthesia (19.2 percent vs 10.5 percent), elevated ALT (4.1 percent vs 13.2 percent) and elevated AST (5.5 percent vs 13.2 percent).
Dubreuil and colleagues reported that about 80 percent of patients in both groups received the planned number of cycles of therapy at the specified dosages.
The objective response rate was 35.1 percent with LV5FU2 and 36 percent with the gemcitabine regimen. The four-month PFS was 55.6 percent with LV5FU2 and 54 percent with gemcitabine. Median PFS was 5.9 months with LV5FU2 and 4.9 months with gemcitabine.
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 percent vs 41 percent) and 18 months (34 percent vs 13 percent).