Perioperative FOLFOX4 for CRC With Liver Metastases Showed No OS Benefit

October 19, 2013

No difference in overall survival was seen for surgery with or without FOLFOX4 in patients with initially resectable liver metastases from colorectal cancer, according to the results of a new study.

[[{"type":"media","view_mode":"media_crop","fid":"18038","attributes":{"alt":"Liver metastases of a colorectal tumor visible within abdominal region of image.","class":"media-image media-image-right","id":"media_crop_9380211366774","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"1216","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Liver metastases of a colorectal tumor visible within abdominal region of image.","typeof":"foaf:Image"}}]]No difference in overall survival was seen for surgery with or without FOLFOX4 in patients with initially resectable liver metastases from colorectal cancer, according to the results of the phase III EORTC 40983 trial published online in the Lancet Oncology.

Previously published results of this study had shown that perioperative chemotherapy with FOLFOX4 conferred an increased progression-free survival. In the discussion of these extended follow-up results, the researchers, led by Bernard Nordlinger, MD, of the Ambroise Paré Hospital, France, pointed out that the trial was powered to detect a difference in progression-free survival and that overall survival was a secondary endpoint.

“We believe that our findings do not modify the conclusion of the previous publication-ie, that perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible patients,” the researchers wrote.

The study was a multi-institutional study enrolling 364 patients aged 18 to 80 years who had colorectal cancer and up to four liver metastases. Patients were randomly assigned to receive surgery with or without perioperative FOLFOX4. The FOLFOX4 regimen consisted of six 14-day cycles of oxaliplatin, folinic acid, and fluorouracil before and after surgery. This study looked at overall survival results at a median follow-up of 8.5 years.

At 8.5 years, no significant differences between the treatment groups were found for overall survival when looking at all patients randomized and eligible patients alone. Fifty-nine percent of patients assigned to perioperative chemotherapy had died compared with 63% of patients assigned to surgery alone, a non-significant difference.

The median overall survival in all patients assigned FOLFOX4 was 61.3 months compared with 54.3 months for surgery alone. Overall survival among patients considered eligible was 63.7 months for the FOLFOX4 group compared with 55 months for surgery alone. Five-year overall survival was 51.2% in the perioperative group compared with 47.8% in the surgery alone group.

In an editorial discussing the research, Yuman Fong, MD, of Memorial Sloan-Kettering Cancer Center, called the result surprising and cautioned that it be interpreted with care.

“As discussed well by Nordlinger and colleagues, their follow-up study was underpowered to prove the significance of the 5% between-group difference in 5-year overall survival,” Fong wrote. “Furthermore, only 115 (63%) patients in the perioperative chemotherapy group received postoperative chemotherapy. Thus, the inability to show a significant difference in overall survival might be a result of inadequate duration of chemotherapy, especially since adjuvant chemotherapy has previously been shown to be important in the treatment of resected, advanced stage colorectal cancer.”

Nordlinger and colleagues suggested additional studies of the efficacy of FOLFOX4 and encouraged clinicians to “participate in new trials for resectable liver metastasis from colorectal cancer, such as the BOS-2 trial.”