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Bevacizumab added to chemotherapy improved survival in NSCLC
Bevacizumab plus paclitaxel-carboplatin led to a 27% improvement in overall survival, compared with chemotherapy alone.
Adding bevacizumab to paclitaxel and carboplatin chemotherapy significantly improved overall survival in patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non–small cell lung cancer, according to a phase-3 trial published in The New England Journal of Medicine.
Based on this study, the FDA approved bevacizumab (Avastin, Genentech) as a first-line treatment with paclitaxel and carboplatin chemotherapy for patients with this advanced form of lung cancer.
“This is the first large, randomized clinical study in which a targeted therapy, combined with chemotherapy, extended survival beyond one year in patients with advanced lung cancer,” Alan B. Sandler, MD, director of medical thoracic oncology at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said in a press release. “The results of this study have changed the treatment standard of care for this devastating disease, an important step forward for patients with advanced lung cancer.”
Adding bevacizumab
In this randomized, open-label, multicenter trial, researchers enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. They excluded patients with squamous tumors, central nervous system metastases, clinically significant hemoptysis (coughing up a half-teaspoon or more of red blood), inadequate organ function or performance status (Eastern Cooperative Oncology Group performance status >1), unstable angina and those receiving therapeutic anticoagulation.
The researchers treated patients with 200 mg/m2 paclitaxel and carboplatin (AUC=6 mg/mL/minute) chemotherapy either with or without 15 mg/kg bevacizumab. They administered chemotherapy with bevacizumab on day one every 21 days for six cycles. After completion of chemotherapy, they administered bevacizumab on day one every 21 days until disease progression or development of intolerable toxicity.
After the baseline evaluation, the researchers assessed tumor status every six weeks for 24 weeks, every nine weeks for the remainder of therapy and every 12 weeks post-therapy.
According to the study, patients receiving bevacizumab plus chemotherapy had approximately a 27% improvement in overall survival, compared with patients who received chemotherapy alone. This was based on a hazard ratio of 0.79.
Median survival of patients treated with bevacizumab plus chemotherapy was 12.3 months vs. 10.3 months for patients treated with chemotherapy alone. One-year survival was 51% for patients receiving bevacizumab plus chemotherapy vs. 44% for patients who received chemotherapy alone. Two-year survival was 23% vs. 15%, respectively.
The researchers also found that patients treated with bevacizumab plus chemotherapy experienced a 52% improvement in progression-free survival based on a hazard ratio of 0.66. Median progression-free survival was 6.2 months for patients treated with bevacizumab plus chemotherapy, compared with 4.5 months for patients who received chemotherapy alone.
The response rate as determined by the researchers was 35% (133/381) in the group receiving bevacizumab plus chemotherapy, compared with 15% (59/392) in the group receiving chemotherapy alone. Progression-free survival and response rate were based on investigator assessments and were not independently verified.
According to the study, some severe adverse events were significantly higher among patients receiving bevacizumab plus chemotherapy compared with patients receiving chemotherapy alone. They included hypertension, proteinuria, bleeding, neutropenia, febrile neutropenia, thrombocytopenia, hyponatremia, rash and headache.
Neutropenia occurred in 26% (109 of 427) of patients treated with bevacizumab plus chemotherapy and 17% (74 of 440) of patients who received chemotherapy alone. The rate of hemoptysis requiring medical intervention for the bevacizumab plus chemotherapy was 1.9% (8/427), compared with 0.2% (1 of 440) for the chemotherapy alone.
There were 15 deaths related to the adverse treatment effects in patients treated with bevacizumab plus chemotherapy, of which five were due to pulmonary hemorrhage, five were due to complications of febrile neutropenia and the remainder were due to other sites of hemorrhage and a probable pulmonary embolism.
For patients treated with chemotherapy alone, two deaths related to the adverse effects of treatment occurred, of which one was from gastrointestinal hemorrhage and one from febrile neutropenia.
The American Cancer Society estimates that in the United States this year, lung cancer will kill more people than breast, prostate, colon, liver and kidney cancers combined, making it the leading cause of cancer death among Americans. Because most lung cancers are diagnosed during a late stage of the disease, only about 15% of patients live five years.
For more information:
- Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non–small cell lung cancer. N Engl J Med. 2006;355:2542-2550.