Genentech and FDA ( Food and Drug Administration ) informed HealthCare Providers of important new safety information regarding Avastain ( Bevacizumab ).
Tracheoesophageal fistula has been seen in a study combining concurrent chemotherapy and radiation plus Avastin in patients with limited-stage small cell lung cancer ( SCLC ).
Avastin is not indicated for use in small cell lung cancer.
In an investigator-sponsored multicenter, single-arm phase II trial, patients with limited-stage SCLC received four cycles of concurrent Irinotecan, Carboplatin, radiation therapy, and Bevacizumab followed by maintenance Bevacizumab for up to 6 months.
There have been two confirmed serious adverse events of tracheoesophageal fistula ( one fatal ) reported in the first 29 patients enrolled in the study. A third, fatal event ( upper aerodigestive tract hemorrhage and death of unknown cause ), was also reported, in which tracheoesophageal fistula was suspected but not confirmed.
All three events occurred during the Bevacizumab maintenance phase of the study in the context of persistent esophagitis.
As of March 22, 2007, six cases of TE fistula have also been reported in other lung and esophageal cancer studies involving the use of Avastin and chemotherapy alone or with concurrent radiation treatment.
There is limited information in the published literature on the background rate of tracheoesophageal fistula in patients with limited-stage small cell lung cancer, but is estimated to be < 1%.
The incidence of tracheoesophageal fistula observed in this trial to date exceeds this rate. Due to the small number of patients treated in the setting of limited-stage small cell lung cancer and the non-randomized nature of this trial, it is not possible to distinguish the toxicity observed in this trial from other risk factors for the development of tracheoesophageal fistula, such as intra-thoracic organ sensitivity from chemotherapy and radiotherapy alone.
This study has been closed to further accrual as of March 12, 2007.
A description of cases of gastrointestinal tract fistula formation in patients with colorectal cancer and other types of cancer treated with Avastin in clinical studies and post-marketing reports is included in the current US prescribing information.
. Genentech intends to revise the Avastin package insert to include more detailed information regarding the incidence of all cases of fistula in patients treated with Bevacizumab.
Avastin is currently approved for the first-line and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy, in addition to the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer in combination with Carboplatin and Paclitaxel.
Source: FDA, 2007