Amgen announced the presentation of detailed results of a phase 3 study with Vectibix (panitumumab) and best supportive care (BSC) compared to BSC alone. The study met its primary endpoint, demonstrating a statistically significant improvement in overall survival (OS) in patients with chemorefractory wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC; n=377 total).
This is the first phase 3 Vectibix study to include an analysis of efficacy of Vectibix by wild-type KRAS (exon 2) and in wild-type RAS tumour mutation status in its primary analysis, providing important information about OS in these populations. These results, in addition to secondary endpoint data, were presented at the 2016 Gastrointestinal Cancers Symposium (GICS) in San Francisco.
The study showed that patients with wild-type KRAS (exon 2) mCRC treated with Vectibix and BSC achieved a median OS of 10 months compared to 7.4 months for patients treated with BSC alone (hazard ratio [HR]=0.73, 95 per cent confidence interval [CI]=0.57-0.93, p=0.0096). Data from a key secondary endpoint showed that patients with wild-type RAS (absence of mutations in exons 2, 3 and 4 of KRAS and NRAS) mCRC treated with Vectibix and BSC achieved a median OS of 10 months compared to 6.9 months for patients treated with BSC alone (n=270; HR=0.70, 95 per cent CI=0.53-0.93, p=0.0135). Patients with mutant RAS mCRC did not benefit from Vectibix treatment (n=54; OS HR=0.99, 95 percent CI=0.49-2.00). The safety profile was comparable to the known safety profile of Vectibix when administered as a single agent, with skin, nail, gastrointestinal and electrolyte disorders being the most frequently reported adverse events.
"Amgen has played a significant role in the advancement of personalized medicine, applying cutting-edge science and technology in our efforts to target therapies to the patients who are most likely to benefit. Amgen is committed to understanding cancer biology through studies like this," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "As well as providing additional insights into the way Vectibix works in mCRC, these data support expanding biomarker screening to include wild-type RAS."
Colorectal cancer is the third most common cancer worldwide, with approximately 1.2 million cases occurring globally each year. Approximately 20 per cent of colon cancers are diagnosed at the metastatic stage, when the disease has already spread to distant organs, a diagnosis associated with only a 12 per cent five-year survival rate. Using molecular approaches to identify unique genetic signatures in mCRC has the potential to help improve treatment outcomes. Of the few biomarkers in colorectal cancer, RAS genes (KRAS, NRAS) have a validated impact on treatment outcomes.
This phase 3 global, multicenter, randomized, open-label study was designed to evaluate OS with Vectibix and BSC compared to BSC alone in patients with chemorefractory wild-type KRAS (exon 2) mCRC.
Key secondary endpoints included progression-free survival (PFS) in patients with wild-type KRAS mCRC, as well as OS and PFS in patients with wild-type RAS (absence of mutations in exons 2, 3 and 4 of KRAS and NRAS) mCRC, objective response rate (ORR) and safety in both wild-type KRAS (exon 2) and wild-type RAS groups.
Patients were randomized 1:1 to receive 6 mg/kg of Vectibix every 14 days and BSC, or BSC alone (as defined by the investigator). There were a total of 377 patients enrolled: 324 out of 377 subjects with RAS mutation status determined (86 percent ascertainment rate); out of 324, 270 had wild-type RAS (83 percent), 54 were found to be mutant RAS (17 percent), 189 patients for KRAS (exon 2) group for Vectibix and BSC.
Treatment with Vectibix combined with BSC in patients with wild-type KRAS resulted in median PFS of 3.6 months versus 1.7 months with BSC alone (HR=0.51, 95 percent CI=0.41-0.64, p=0.0001). In patients with wild-type RAS, the Vectibix combination resulted in median PFS of 5.2 months versus 1.7 months with BSC alone (HR=0.46, 95 percent CI=0.35-0.59, p=0.0001).
For patients with wild-type KRAS, ORRs were 27.0 percent with Vectibix versus 1.6 percent with BSC (HR=24.9, 95 percent CI=7.5-123.8, p<0.0001). For patients with wild-type RAS, ORRs were 31.0 percent with Vectibix versus 2.3 percent for BSC (ODDS Ratio=20.0, 95 percent CI=5.9-101.6, p<0.0001).
Patients with mutant RAS mCRC did not benefit from Vectibix treatment (OS HR=0.99, 95 percent CI=0.49-2.00). No new safety signals were seen in this study. The safety profile was comparable to the known safety profile of Vectibix when administered as a single agent, with skin, nail, gastrointestinal and electrolyte disorders being the most frequently reported adverse events.
Vectibix is the first fully human monoclonal anti-epidermal growth factor receptor (EGFR) antibody approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer (mCRC). Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.
In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.