CHICAGO -- The combination of two targeted therapies appears to be a more effective, but less toxic, alternative to chemotherapy for second line treatment of unresectable non-small-cell lung cancer.
CHICAGO, Oct. 30 -- The combination of two targeted therapies appears to be a more effective, but less toxic, alternative to chemotherapy for second line treatment of unresectable non-small-cell lung cancer.
In a small multicenter phase II trial that compared standard chemotherapy with chemotherapy plus Avastin (bevacizumab) or Avastin plus Tarceva (erlotinib) for unresectable recurrent or refractory disease, six month results "appear to favor the Avastin combinations," said Roy S. Herbst, M.D., of M.D. Anderson Cancer Center in Houston.
Dr. Herbst reported results of the trial here Friday at the International Association for the Study of Lung Cancer symposium on malignancies of the chest and head and neck.
Median progression-free survival was 3.0 months in the chemotherapy arm, versus 4.8 months for Avastin plus chemotherapy and 4.4 months in the Avastin-Tarceva arm.
The six-month progression-free survival rate was 33.6% in the Avastin-Tarceva arm versus 30.5% in the Avastin-chemotherapy arm and 21.5% in the control arm, he said.
The response rates, either complete or partial, in the Avastin-Tarceva arm was 17.9% at six months versus 12.5% in the Avastin-chemotherapy arm and 12.2% in the control arm. The six-month complete or partial response rate-stable disease rate was 52.5% in the Avastin-chemotherapy arm, 51.3% in the Avastin-Tarceva arm and 39% in the chemotherapy arm, Dr. Herbst said.
At six months, the overall survival was 78.3% in the Avastin-Tarceva arm, and 72.1% in the Avastin plus chemotherapy arm versus 62.4% in the chemotherapy arm.
But in no case did the results reach statistical significance, which Dr. Herbst said, "probably reflected the small numbers in this trial."
As expected there were more bleeding events in the two Avastin arms, with two grade 5 bleeding events in each of the Avastin arms versus one grade 3-4 bleeding events in the chemotherapy arm. The grade 5 events included one pulmonary hemorrhage in the Avastin-chemotherapy arm.
Dr. Herbst said these data extend results reported at the American Society of Clinical Oncology meeting last June that reported efficacy for Avastin plus chemotherapy in the first-line setting.
Moreover, since there were also data that demonstrated the efficacy of Tarceva in second- and third-line settings, "it seemed natural that we should investigate the combination in a randomized trial in patients who have experienced disease progression following platinum-based therapy for advanced disease," he said.
All patients had histologically confirmed non-squamous NSCLC. Randomization was on a 1:1:1 basis to Taxotere (docetaxel) or Alimta (pemetrexed) plus placebo, versus Taxotere or Alimta plus Avastin, versus Avastin plus Tarceva.
Patients in all arms were generally well balanced, but there were 22 women (56.4%) in the Avastin-Tarceva arm, versus 17 women (42.5%) in the Avastin-chemotherapy arm and 16 or 39% in the control arm.
The primary endpoint was efficacy measured by disease-free survival.
One hundred and twenty patients were randomized and treated from August 2004 to November 2005 with 42 patients in the control arm, 39 in the chemotherapy plus Avastin arm and 39 randomized to Avastin plus Tarceva.
Dr. Herbst said two randomized trials are now underway that will further address the roles of Avastin and Tarceva in NSCLC.
The first is an 1,150-patient trial that will randomize patients who have progressive disease or significant toxicity after four cycles of chemotherapy plus Avastin to Avastin plus placebo or Avastin-Tarceva.
The second, a 650-patient trial, will randomize patients with chemotherapy-resistant or recurrent NSCLC to Tarceva plus placebo or Tarceva plus Avastin.