Italian Trial Shows Benefit of Dose-Dense Adjuvant Therapy With Sequential Epirubicin-Cyclophosphamide-Paclitaxel in Early Node-Positive Breast Cancer

“In an Italian 2×2 phase III trial reported in The Lancet, Del Mastro et al found that dose-dense adjuvant therapy with sequential epirubicin, cyclophosphamide, and paclitaxel (EC-P) with or without fluorouracil (5-FU) increased disease-free survival vs standard-interval therapy in early-stage node-positive breast cancer. No benefit of adding 5-FU to EC-P was observed.

“In this open-label trial, 2,091 patients from 81 Italian centers were randomly assigned 1:1:1:1 between April 2003 and July 2006 to receive adjuvant dose-dense chemotherapy every 2 weeks with pegfilgrastim (Neulasta) support with 5-FU plus EC-P (FEC-P, n = 500) or EC-P (n = 502) or standard-interval chemotherapy every 3 weeks with FEC-P (n = 544) or EC-P (n = 545). The primary endpoint was disease-free survival in the intention-to-treat population, with primary comparisons between every-2-week vs every-3-week schedules and FEC-P vs EC-P.

“Overall, patients had a median age of 51 to 53 years, 47% to 55% were postmenopausal, 59% to 63% had lumpectomy, 48% to 52% had T1 tumors, 57% to 64% had one to three positive nodes, 43% to 49% had grade 3 tumors, 21% to 24% were HER2-positive, 77% to 81% were estrogen or progesterone receptor–positive, and 43% to 50% had ≥ 20% Ki67-positive cells.

“The investigators concluded: ‘In patients with node-positive early breast cancer, dose-dense adjuvant chemotherapy improved disease-free survival compared with standard interval chemotherapy. Addition of fluorouracil to a sequential EC-P regimen was not associated with an improved disease-free survival outcome.’ ”


Drug Shows Promise for Subset of Stage III Colon Cancer Patients

This article describes the results of a clinical trial—a research study with volunteer patients. The trial tested adding a third drug to a standard two-drug chemotherapy treatment for colorectal cancer. The standard treatment consists of the drugs fluorouracil and leucovorin. It is given to patients after tumor-removal surgery to keep the cancer from coming back (recurrence). In the trial, a third drug called irinotecan was added. The researchers found that stage III patients whose tumors tested positive for a genetic change called CIMP benefitted from the irinotecan addition. Stage III CIMP-negative patients did not.

“When added to the standard chemotherapy treatment — fluorouracil and leucovorin — adjuvant irinotecan therapy improved overall survival rates for patients with the CpG island methylator phenotype (CIMP). CIMP is seen in about 10 to 20 percent of colorectal cancers. Patients with CIMP-negative tumors, however, exhibited significant harm from the addition of irinotecan — overall survival was 68 percent compared with 78 percent for those receiving the standard treatment alone.

“Our results serve as an example that the molecular characterization of individual tumors may help to determine the most appropriate treatment for patients with colon cancer,” said lead study author Stacey Shiovitz, MD, from the department of medicine, University of Washington, Seattle, WA, and the clinical research division of Fred Hutchinson Cancer Research Center, also in Seattle. “Based on our findings, identification of a tumor’s CIMP status should play a greater role in the clinical setting.”


Higher Bar Set for Trials in Advanced Colorectal Cancer

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to compare four different treatments for metastatic colorectal cancer (mCRC). All patients took a combination of chemotherapy drugs; either FOLFIRI [which combines folinic acid, fluorouracil and irinotecan] or FOLFOX [folinic acid, 5-fluorouracil and oxaliplatin]. Patients also took a targeted drug alongside the chemo; either bevacizumab (aka Avastin) or cetuximab (Erbitux). All four treatment combinations resulted in similar survival times—a median of 29 months. Compared to other clinical trials, this is a relatively long survival time. Based on these results, oncologists will now have more options for treating their patients according to patients’ preferences and side effects.

“Patients with KRAS wild-type metastatic colorectal cancer (mCRC) receiving first-line treatment with a chemotherapy backbone plus bevacizumab or cetuximab survived for a median of 29 months, the longest median survival time reported in a major trial of these severely ill patients.

“Importantly, survival times were the same, whether patients received the anti–vascular endothelial growth factor bevacizumab (Avastin, Genentech) or the anti–epidermal growth factor receptor (EGFR) cetuximab (Erbitux, Bristol-Myers Squibb), or whether they received FOLFOX or FOLFIRI, results from the long-awaited Phase III CALGB/SWOG 80405 trial showed.

“ ‘What this tells us is that either FOLFIRI [folinic acid, fluorouracil and irinotecan] or FOLFOX [folinic acid, 5-fluorouracil and oxaliplatin] with either bevacizumab or cetuximab are perfectly reasonable options,’ said Alan P. Venook, MD, the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco.”


No Difference in Response Rate but Overall Survival Benefit With First-Line FOLFIRI/Cetuximab vs FOLFIRI/Bevacizumab in Metastatic Colorectal Cancer

Editor’s note: Researchers organized a clinical trial with volunteer patients to compare two treatments for people with metastatic colorectal cancer. All patients in the trial took a chemotherapy treatment called FOLFIRI. (FOLFIRI combines the drugs fluorouracil, leucovorin, and irinotecan.) Some of the patients were also given the drug cetuximab, and the rest took the drug bevacizumab along with FOLFIRI. The patients who took FOLFIRI plus cetuximab survived significantly longer than the patients who took FOLFIRI plus bevacizumab.

“In a European phase III FIRE-3 trial reported in The Lancet Oncology, Heinemann et al found no difference in response rate, the primary endpoint, between FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus the anti-EGFR antibody cetuximab (Erbitux) vs FOLFIRI plus the anti-VEGF-A antibody bevacizumab (Avastin) in first-line treatment of patients with metastatic colorectal cancer. The cetuximab-containing regimen was associated with a significant overall survival advantage…

“In this open-label trial, 592 patients with KRAS exon 2 codon 12/13 wild-type metastatic colorectal cancer aged 18 to 75 years from centers in Germany and Austria were randomly assigned between January 2007 and September 2012 to receive FOLFIRI plus either cetuximab (n = 297) or bevacizumab (n = 295). The primary endpoint was objective response in the intention-to-treat population. The study has completed recruitment, but patient follow-up is ongoing.”