Roche has announced that the FDA ( Food and Drug Administration ) has approved a new use of Avastin ( Bevacizumab ) in combination with fluoropyrimidine-based Irinotecan or Oxaliplatin chemotherapy for people with metastatic colorectal cancer ( mCRC ). The new indication will allow people who received Avastin plus an Irinotecan or Oxaliplatin containing chemotherapy as an initial treatment for mCRC to continue to receive Avastin plus a different Irinotecan or Oxaliplatin containing chemotherapy after their cancer worsens.
Avastin in combination with fluoropyrimidine-Irinotecan or fluoropyrimidine-Oxaliplatin based chemotherapy is now indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen. The approval is based on positive results from the phase III ML18147 study, which were presented at the 2012 American Society of Clinical Oncology ( ASCO ) annual meeting and showed that people who continued to receive an Avastin-based regimen after their cancer worsened lived longer than people who switched to chemotherapy alone.
Avastin is the only biologic medicine approved by the FDA to treat people with mCRC in combination with intravenous 5FU-based chemotherapy as an initial treatment, as treatment for people whose cancer has worsened after chemotherapy alone, and now as a treatment for people whose cancer has worsened after initial treatment with an Avastin-based regimen. This is the third approval for Avastin in metastatic colorectal cancer based on improved overall survival. Avastin is not indicated for adjuvant treatment of colon cancer.
Avastin is approved in Europe in combination with fluoropyrimidine-based chemotherapy for the treatment of adult patients with metastatic carcinoma of the colon or rectum. The European product information has been updated based on the positive results of the phase III ML18147 study with an implementation date of december 12, 2012 allowing people with metastatic colorectal cancer who received Avastin plus chemotherapy as a first-line treatment to continue to receive Avastin plus chemotherapy after their cancer worsens as part of their second-line treatment.
ML18147 was a randomised, open-label, phase III, multicentre, multinational trial evaluating the efficacy and safety profile of Avastin plus standard second-line chemotherapy in 820 patients with metastatic colorectal cancer whose disease had progressed following Avastin plus standard first-line chemotherapy ( Irinotecan or Oxaliplatin-based ). Patients were randomised at progression to one of two treatment arms: Arm A: chemotherapy plus Avastin ( equivalent of 2.5 mg/kg i.v. per week ); Arm B: chemotherapy alone.
The risk of death was reduced by 19% for people who received Avastin in combination with standard chemotherapy in both the first- and second-line compared to those who received chemotherapy alone ( hazard ratio, HR=0.81, p=0.0057 ). Median overall survival was 11.2 months compared to 9.8 months.
The risk of the cancer worsening or death ( progression-free survival; PFS ) was reduced by 32% ( HR=0.68, p less than 0.0001 ). Median progression-free survival was 5.7 months compared to 4.1 months.
There was no significant difference in response rate between treatment arms. Overall survival and progression-free survival were calculated from the time patients were randomised to the second-line treatment. Adverse events in ML18147 were consistent with those seen in previous pivotal trials of Avastin in metastatic colorectal cancer.
The primary endpoint of the study was overall survival measured from the time patients were randomized to the second-line treatment. The secondary efficacy endpoints of the study included progression-free survival, overall response rate and safety profile.
Source: Roche, 2013