Genentech, Inc. has announced an update for the previously reported Roche-sponsored international Phase III clinical study (AVAiL) of Avastin (bevacizumab) in combination with gemcitabine and cisplatin chemotherapy, in patients with advanced, non-squamous, non-small cell lung cancer (NSCLC).
The update confirmed the clinically and statistically significant improvement in the primary endpoint of progression free survival (PFS) for the two different doses of Avastin studied in the trial (15 mg/kg and 7.5 mg/kg) compared to chemotherapy alone. The study did not demonstrate a statistically significant prolongation of overall survival, a secondary endpoint, for either dose in combination with gemcitabine and cisplatin chemotherapy compared to chemotherapy alone. Median survival of patients in all arms of the study exceeded one year, longer than previously reported survival times in this indication.
Importantly, the Genentech pivotal Phase III U.S. study (E4599) of Avastin plus carboplatin and paclitaxel chemotherapy showed a statistically significant improvement in overall survival for patients with advanced lung cancer compared to chemotherapy alone (25 percent improvement, hazard ratio 0.80). In 2006, the Food and Drug Administration (FDA) approved Avastin for the first-line treatment of unresectable, locally advanced, recurrent metastatic, non-squamous, NSCLC on the basis of E4599. The study had a primary endpoint of overall survival and tested 15 mg/kg of Avastin with a different chemotherapy regimen (carboplatin and paclitaxel) than the AVAiL study.
“The statistically significant improvement in overall survival observed in E4599, as well as the safety and improvement in progression-free survival in AVAiL and E4599, give us confidence in Avastin’s safety and efficacy for patients with advanced, non-squamous, non-small cell lung cancer. These studies reinforce our belief that Avastin is an important treatment option for patients with this most common form of lung cancer,” said Hal Barron, M.D., senior vice president, Development and chief medical officer.
No new safety signals for Avastin were observed in the study, and there were no clinically meaningful differences in safety between the two doses of Avastin.
AVAiL is an international study, conducted outside of the U.S., that enrolled 1,043 patients with previously untreated, advanced, non-squamous, NSCLC. The study met its primary endpoint of progression-free survival, defined as the time from randomization to the first event of progression or death, and was presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in 2007. Secondary endpoints included overall survival, response rate, time to treatment failure and safety. Patients were randomized to receive cisplatin (80 mg/m2 on Day 1) and gemcitabine (1,250 mg/m2 on Day 1 and Day 8) chemotherapy every three weeks for up to six cycles plus either Avastin 15 mg/kg or Avastin 7.5 mg/kg every three weeks (until disease progression), or placebo. Physicians and patients in the study were blinded to treatment with Avastin but not dose.