FDA Drug Approval Summary: Bevacizumab (Avastin®) Plus Carboplatin and Paclitaxel as First-Line Treatment of Advanced/Metastatic Recurrent Nonsquamous Non-Small Cell Lung Cancer

Abstract

After completing this course, the reader will be able to:1. Describe the bevacizumab mechanism of action.2. List the current bevacizumab indications.3. Discuss the role of bevacizumab in the treatment of specific non-small cell lung cancer histologies.4. Describe the clinical trial design leading to bevacizumab approval by the FDA. 5. Identify the major adverse events associated with bevacizumab treatment.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTOn October 11, 2006, the U.S. Food and Drug Administration granted approval for bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), administered in combination with carboplatin and paclitaxel, for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic, nonsquamous, non-small cell lung cancer (NSCLC). Approval is based on a significant improvement in overall survival (OS).A randomized, open label, multicenter clinical trial, conducted by the Eastern Cooperative Oncology Group (ECOG), in chemotherapy-naïve patients with stage IIIB/IV nonsquamous NSCLC, evaluated bevacizumab plus carboplatin and paclitaxel (BV/CP, n ‫؍‬ 434) versus carboplatin and paclitaxel alone (CP, n ‫؍‬ 444). Exclusion of patients with squamous or predominantly squamous histology was based on life-threatening or fatal hemoptysis occurring in 4 of 13 patients with squamous histology who received a BV/CP regimen in a phase II study.Among the 878 randomized patients, the median age was 63, 46% were female, 76% had stage IV disease, 12% had stage IIIB disease with malignant pleural effusion, 11% had recurrent disease, and 40% had an ECOG performance status score of 0.OS was significantly longer in patients receiving BV/CP Severe and life-threatening adverse events occurring more frequently in patients receiving BV/CP were neutropenia (27% versus 17%), fatigue (16% versus 13%), hypertension (8% versus 0.7%), infection without neutropenia (7% versus 3%), thrombosis/embolism (5% versus 3%), pneumonitis or pulmonary infiltrate (5% versus 3%), infection with grade 3 or 4 neutropenia (5% versus 2%), febrile neutropenia (5% versus 2%), hyponatremia (4% versus 1%), proteinuria (3% versus 0), and headache (3% versus 0.5%). Fatal, treatment-related adverse events in patients receiving bevacizumab were pulmonary hemorrhage (2.3% versus 0.5%), gastrointestinal hemorrhage, central nervous system infarction, gastrointestinal perforation, myocardial infarction, and neutropenic sepsis.The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, congestive heart failure, and neutropenic sepsis. The most common adverse events in patients receiving bevacizumab are asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermati...

Placental isoform glutathione S-transferase and P-glycoprotein expression in advanced nonsmall cell lung cancer

“…Platinum compounds still are used largely in treatment protocols for patients with advanced NSCLC in combination with other regimens. [26][27][28] Furthermore, novel treatments that target the glutathione pathway currently are under investigation. 29,30 On the basis of our results, the expression of GST-pi, P-gp, or both proteins may contribute to a more accurate prediction of outcome, giving the opportunity for better selection of patient-oriented therapy.…”

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

“…223 The most commonly reported Bevacizumabrelated toxicities were bleeding/haemorrhage, hypertension, proteinuria, and venous or arterial thromboembolic events 224 . In addition, the British National Formulary emphasises the risks of gastrointestinal perforation and fistulas, and that treatment should be withheld before elective surgery and avoided for at least 28 days after major surgery or until the wound is fully healed 184 .…”

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

“…A few examples are outlined: (1) targeting of specific cell signaling pathways such as the epidermal growth factor inhibitorscetuximab (Erbitux), a chimeric (mouse/human) monoclonal antibody (mAb), used in the treatment of colorectal cancer and head and neck carcinoma [52][53][54][55], trastuzumab (Herceptin), an anti-HER2 mAb, used against breast tumors and metastatic gastric cancer-expressing HER2 [56]; (2) interference with tumor angiogenesis-bevacizumab (Avastin), an anti-VEGF-A humanized mAb, used against colorectal, lung, breast, glioblastoma, kidney, and ovarian tumors [57,58]; (3) targeting of specific tumor antigens-rituximab (MabThera), an anti-CD20 mAb, used against non Hodgkin's lymphoma [59]. A growing number of targeted treatments have reached the clinical setting; some replacing the conventional systemic treatments and others are used in conjunction with them to allow application of lower doses of the later, more toxic, drugs.…”