Global Insight Perspective | |
Significance | Upon release of the results of the CRYSTAL study, which evaluated the benefits of Erbitux (cetuximab) in metastatic colorectal cancer patients, Roche touted Avastin (bevacizumab) as the only biologic able to improve overall survival when used as a first-line therapy in patients carrying a non-mutated version of the K-Ras gene. |
Implications | Roche argues that Avastin shows greater benefits than Erbitux in this setting. Nevertheless, those are two independent trials and a head-to-head study could ensue. |
Outlook | As Erbitux has just clinched European label extension in the first-line treatment of wild-type K-Ras metastatic colorectal cancer patients, it is instrumental for Roche to convince of Avastin's superiority to retain market share. |
Swiss pharmaceutical giant Roche has promoted its oncology drug Avastin (bevacizumab) as superior to rival treatment Erbitux (cetuximab; Merck KGaA, Germany) in metastatic colorectal cancer (mCRC). The move comes after results from the CRYSTAL study, which evaluated Erbitux as a first-line therapy in combination with chemotherapy in mCRC patients, were released at the 33rd Congress of the European Society for Medical Oncology (ESMO) held in Stockholm, Sweden. In the CRYSTAL trial, Erbitux missed the secondary endpoints of overall survival (OS) in the general study population as well as OS in mCRC patients carrying the K-Ras wild type (wt) allele (see table). On the other hand, Avastin as a first-line therapy in combination with chemotherapy demonstrated clear OS and progression-free survival (PSF) in both patient populations in the 2107 study (see table). Roche therefore concluded that Avastin remains the only biologic to show OS benefits in K-Ras wt mCRC patients when used as a first-line therapy in combination with chemotherapy.
Outcomes of Avastin 2107 and Erbitux CRYSTAL Clinical Studies | ||||
Avastin vs. control | Statistically Significant? | Erbitux vs. control | Statistically Significant? | |
OS in K-Ras wt patients | 27.7 vs. 17.6 months | Yes | 24.9 vs. 21.0 months | No |
OS in general study population | 20.3 vs. 15.6 months | Yes | 19.9 vs. 18.6 months | No |
PSF in K-Ras wt patients | 13.5 vs. 7.4 months | Yes | Not Provided | Not Applicable |
PSF in K-Ras mutant patients | 9.4 vs. 5.5 months | Yes | Not Provided | Not Applicable |
Source: Roche | ||||
According to a March 2008 article published in CA: A Cancer Journal For Clinicians, around 148,810 new cases of large bowel cancer are diagnosed annually in the United States. Of those, 108,070 cases are colon cancers and 40,740 rectal cancers. CRC is responsible for approximately 9 percent of all U.S. cancer deaths, making it the second most deadly cancer in the United States, second only to lung cancer. According to Merck KGaA, over 370,000 people develop colorectal cancer in Europe annually and around 25% of patients suffer from the metastatic form of the disease. Prognosis is poor as five-year survival rates stand at 5%.
Outlook and Implications
Roche is positioning its drug as the best option available for the treatment of mCRC. This move is strategic as Erbitux recently clinched European approval as a first-line therapy in combination with chemotherapy in the treatment of K-Ras wt mCRC patients (see Germany: 24 July 2008: EU Approval for New Erbitux Setting as Merck Vows to Triple Japanese Sales) and Roche will be eager to curb Erbitux's market penetration in this setting as much as possible. Up until now, Avastin had increasingly emerged as a standard of care in first-line treatment while Erbitux had seen rapid uptake as a third-line treatment. In the meantime, both Erbitux and Avastin hold a substantive share in the second-line setting. Avastin is licensed for use in mCRC patients with any chemotherapy as a first-line therapy and in any subsequent round of treatment (see Switzerland: 28 January 2008: Roche Secures Broad European Label Extension for Avastin in Colorectal Cancer).