Amgen announced results from new retrospective analyses of key studies with Vectibix (panitumumab) in metastatic colorectal cancer (mCRC) patients. The retrospective analysis of the PEAK study in mCRC patients with RAS wild-type primary tumours of left-sided origin showed that patients receiving Vectibix plus Folfox6 as first-line treatment achieved 43.4 months median overall survival (OS), an increase of 11.4 months when compared to Folfox6 plus bevacizumab. Additionally, for this patient population, the retrospective analysis of the PRIME study showed Vectibix plus Folfox4 increased OS by 6.7 months when compared to Folfox4 alone. These data were presented today at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen.
The PEAK and PRIME retrospective analyses, respectively, also showed that mCRC patients with RAS wild-type tumours of left-sided origin receiving Vectibix plus Folfox chemotherapy achieved median progression-free survival (PFS) of 14.6 months, an increase of 3.1 months when compared to Folfox plus bevacizumab, and 12.9 months, an increase of 3.7 months when compared to Folfox chemotherapy alone.
The retrospective analyses found that approximately 80 per cent of tumors originate in the left side of the colon. Additionally, tumours originating in the right side of the colon are currently associated with a poorer prognosis than tumors originating in the left side of the colon. In patients with RAS wild-type mCRC with tumours originating on the right side, a subgroup of patients responded to Vectibix and chemotherapy, achieving numerically higher response rates over chemotherapy with or without bevacizumab. However, no final conclusions can be made regarding the ability to differentiate treatment regimens for patients with right-sided tumors. The safety profile of the use of Vectibix in combination with Folfox-based chemotherapy in mCRC has been previously reported (see summary of EU product safety information below). The aggregate safety data is unchanged by this retrospective analysis of outcomes based on CRC tumor site of origin.
"Data from these retrospective analyses are helping Amgen make important connections between tumor biology and treatment outcomes," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Tumour sidedness is a surrogate for differences in tumor biology and mutation load, potentially providing physicians with another means to help inform the treatment decisions for patients with metastatic colorectal cancer."
Colorectal cancer is the second most common cancer in women and the third in men worldwide, with approximately 1.4 million new cases occurring globally each year. In Europe, it is the second most common cancer, with more than 470,000 new cases each year. Approximately 80 per cent of all colorectal cancers originate in the left side of the colon and 20 per cent originate in the right side.
PRIME was a randomized phase 3 open-label study of first-line Vectibix and Folfox4 combination therapy versus Folfox4 monotherapy in 1,183 adults with untreated mCRC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. The primary endpoints were PFS and OS.
Of the 1,183 patients enrolled in PRIME, 505 had RAS wild-type mCRC, of whom 456 were included in the quality of life analysis (Vectibix and FOLFOX4, n=232; FOLFOX4, n=224). The meta-analysis included PRIME data from 440 patients with RAS wild-type mCRC who were evaluable for OS and early tumour shrinkage (ETS).
PEAK was a randomized phase 2 open-label study of first-line Vectibix and Folfox6 versus bevacizumab and Folfox6 in 285 RAS wild-type mCRC patients. The primary endpoint was PFS. The meta-analysis included PEAK data from 154 patients with RAS wild-type mCRC who were evaluable for OS and ETS.
The '181 study was a randomized phase 3 open-label study comparing Vectibix and Folfiri versus Folfiri alone as second-line treatments in 1,186 wild-type KRAS (exon 2) mCRC patients who progressed on one prior fluoropyrimidine-based mCRC therapy. The co-primary endpoints were PFS and OS.
Vectibix is a fully human anti-epidermal growth factor receptor (EGFR) antibody approved by the European Commission (EC) for the treatment of mCRC. The safety and efficacy of Vectibix have not been studied in patients with renal or hepatic impairment. Vectibix was approved by the EC in December 2007 as a monotherapy for the treatment of patients with EGFR-expressing mCRC with non-mutated (wild-type) KRAS genes after failure of standard chemotherapy regimens.
In April 2015, the EC approved a new use of Vectibix as first-line treatment in combination with Folfiri for the treatment of adult patients with RAS wild-type mCRC.5 In November 2011, the EC expanded the marketing authorization to include indications for the treatment of patients with KRAS wild-type mCRC in first-line in combination with Folfox and in second-line in combination with Folfiri in patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
Globally, over 240,000 patients have been treated with Vectibix and more than 6,000 patients have participated in Amgen-sponsored panitumumab clinical trials.