by Dr. C. H. Weaver M.D. updated 7/2019
Avastin® (bevacizumab) can be effectively combined with standard chemotherapy, checkpoint inhibitor immunotherapy, and medications that target EGFR + NSCLC to delay the progression of cancer and prolong survival in many individuals with newly diagnosed or recurrent non-small cell lung cancer (NSCLC). (1-9)
Avastin belongs to a class of drugs called monoclonal antibodies. Avastin produces its anticancer effects by targeting vascular endothelial growth factor (VEGF) and preventing the interaction of VEGF with its receptors to reduce the growth and spread of cancer cells.
VEGF, a type of protein, is important in a process leading to cellular growth, replication, and spread and to new blood vessel formation. Avastin binds to VEGF and reduces its normal activity. It lessens the growth and spread of cancer cells by inhibiting the growth of new blood vessels and depriving the cancer of nutrients and oxygen and inhibits its growth. Avastin has been approved for the treatment of selected patients with breast cancer, lung cancer, colorectal cancer, kidney cancer, or glioblastoma.
Avastin® Approved for Initial Treatment of Non–Small Cell Lung Cancer
The United States Food and Drug Administration (FDA) approved Avastin® (bevacizumab) for use in combination with Paraplatin®(carboplatin) and Taxol® (paclitaxel) as initial therapy for advanced NSCLC.
The E4599 trial prompted FDA approval of Avastin for the treatment of lung cancer. The trial included 878 patients with locally advanced, metastatic, recurrent, or inoperable NSCLC. One group of patients was treated with Avastin plus Paraplatin and Taxol and another group of patients received Paraplatin/Taxol only as initial therapy.
- One year survival rates were 51% for patients treated with Avastin plus chemotherapy, compared with 44% for those treated with chemotherapy only.(1)
Combining Avastin with Tarceva improves progression-free survival (PFS) over Tarceva alone in patients with EGFR-positive NSCLC.
A total of 228 patients with stage IIIB to IV or recurrent EGFR-positive NSCLC were treated with Tarceva with or without Avastin and directly compared. The interim analysis published in May 2019 reported that, the median PFS was 16.9 months for the combination compared to 13.3 months for Tarceva alone.(8)
Avastin + Tecentriq Checkpoint Inhibitor Immunotherapy
The IMpower150 clinical trial compared Tecentriq immunotherapy in combination with chemotherapy with or without Avastin in people with stage IV or recurrent metastatic non-squamous NSCLC in 1202 previously untreated patients without an EGFR or ALK mutation. Individuals were treated with either one of 3 regimens and directly compared. (9)
- Tecentriq plus carboplatin and paclitaxel
- Tecentriq and Avastin plus carboplatin and paclitaxel
- Avastin plus carboplatin and paclitaxel
The result of the study demonstrated that individuals treated with Tecentriq in combination with Avastin and chemotherapy were more likely to respond to treatment and survive compared to Avastin and chemotherapy. The median survival was improved from 14 to 19 months. The rationale for combining Tecentriq and Avastin with chemotherapy is to target the cancer simultaneously with different medications and to enhance the potential of the immune system to combat the cancer by priming and activating a T cell response against cancer cell antigens.
Avastin® plus Chemotherapy for Treatment of Non–Small Cell Lung Cancer
The combination of Avastin® (bevacizumab), Gemzar® (gemcitabine), and Platinol® (cisplatin) prolonged progression-free survival when compared with chemotherapy alone among patients with NSCLC.
Researchers evaluated the chemotherapy combination of Avastin, Gemzar, and Platinol. Patients were assigned to receive both Platinol and Gemzar along with Avastin, at doses of either 15mg/kg or 7.5mg /kg, or to receive a placebo.
- Patients treated with either dose of Avastin, Gemzar, and Platinol had a significant improvement in progression-free survival when compared with patients who were treated with chemotherapy alone.
- Additionally, the average survival of patients in all arms of the study exceeded one year, which was an improvement from previously reported survival rates.
- Neither dose of Avastin, Gemzar, and Platinol improved overall survival compared with chemotherapy alone.
Researchers conducted a study in order to determine the safety of Avastin in the clinical practice setting versus the clinical trial setting. This type of study is referred to as a Phase IV study.
In this study 2,200 patients with locally advanced, metastatic or recurrent non–squamous NSCLC were evaluated. Patients underwent treatment with Avastin plus chemotherapy for up to six cycles and continued being treated with Avastin alone until their disease progressed.
Side effects were as expected with the incidence in the practice setting generally similar to that reported in clinical trials. Serious (grade 3 or higher) side effects included the following:
- High blood pressure (6%)
- Nausea and vomiting (3%)
- Neutropenia (6%)
- Febrile neutropenia (3%)
- Blood clots (8%)
- Bleeding (4%)
The median overall survival reported in this study was 14.6 months. Overall, efficacy was consistent regardless of which standard chemotherapy regimen was used in combination with Avastin.
The researchers concluded that Avastin combined with standard chemotherapy followed by Avastin alone for patients with advanced non–squamous NSCLC has a manageable safety profile and provides a clinical benefit in the practice setting.
- Genentech. FDA Approves Avastin in Combination With Chemotherapy for First-Line Treatment of Most Common Type of LungCancer.Availableat:<a href="http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=10107.">http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=10107.</a>
- Crinò L, Dansin E, Garrido P, et al. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study. The Lancet Oncology. [Early online publication July 21, 2010].
- Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. Journal of Clinical Oncology. 2009;10;27:1227-34.
- Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. New England Journal of Medicine. 2006; 355: 2542-2550.
- Second Phase III Study of Avastin Plus Chemotherapy Shows Improved Progression-Free Survival in First-Line Non-Squamous, Non-Small Cell Lung Cancer.
- Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin Alone or with Bevacizumab for Non-small Cell Lung Cancer. New EnglandJournal of Medicine. 2006;355:2542-50.
- Genentech provides update on “AVAiL” Phase III study of Avastin plus chemotherapy in first-line, advanced, non–squamous, non–small cell lung cancer [press release]. Genentech Web site. Available at:<a href="http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=11207.">http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=11207.</a>
- Lancet Oncology. 2019 Apr 8. Epub ahead of print.
- Socinski M et al., Atezolizumab for First-Line Treatment of Metastatic non-squamous NSCLC. N Engl J Med. 2018; 378:2288- 2301.