Oncologists Speak on Avastin

A significant survival benefit: Comments from leading oncologists

Ronald B. Natale, MD

"The introduction of Avastin in combination with paclitaxel/carboplatin really represents the next major advance in the first-line treatment of patients with advanced NSCLC….The platinum doublets that were used in those best supportive care studies improved the 1-year survival to 23% to 27%. The newer chemo regimens have pushed that 1-year survival up to about 35% to 37%, but to have a 23% two-year survival is really unprecedented….Avastin plus paclitaxel/carboplatin is the standard of care for all eligible first-line NSCLC patients. It should be offered to all patients who meet the eligibility criteria, which are important to keep in mind, because Avastin plus paclitaxel/carboplatin may give patients an improved survival outcome."

Ronald B. Natale, MD, is the Senior Research Advisor and National Director of the Lung Cancer Research Program for Aptium Oncology and an attending physician at the Cedars-Sinai Outpatient Cancer Center in Los Angeles, California. Dr Natale earned his medical degree from Wayne State University School of Medicine in Detroit, Michigan where he also did his medical residency. He completed a fellowship in hematology/oncology at the Memorial Sloan-Kettering Cancer Center in New York and a research fellowship at the National Cancer Institute. Prior to his current positions, he was a faculty member at the University of Michigan, where he also served as Associate Director of the Comprehensive Cancer Center, and at the University of Southern California, where he served as Associate Director of Medical Oncology.

Dr Natale is internationally renowned for his clinical research efforts in lung and genitourinary cancers. He has published over 250 articles and abstracts, co-authored several books, and presented results of his research at cancer research meetings all over the world. He has been cited as one of the best cancer doctors by Los Angeles Magazine, Good Housekeeping, and in each edition of Best Doctors in America since its inception.

Dr Ronald Natale BIO

Mark F. Kozloff, MD

"[Avastin plus paclitaxel/carboplatin] has statistically increased overall survival and pushed the median overall survival over 12 months. That’s an increase of over 2 months compared with standard chemotherapy doublets of paclitaxel/carboplatin. The benefit of Avastin is both statistically significant, as well as clinically significant."

Mark F. Kozloff, MD, is a Clinical Associate of Medicine in the Section of Hematology/Oncology at the University of Chicago in Chicago, Illinois, and Director of Oncology at the Ingalls Cancer Care Center at Ingalls Memorial Hospital in Harvey, Illinois. He also practices internal medicine in Orland Park and Tinley Park, Illinois, and in Munster, Indiana. Dr. Kozloff earned his medical degree from the University of Michigan in Ann Arbor. He served a residency in internal medicine at Michael Reese Hospital in Chicago and completed a fellowship in hematology at the University of Michigan. He is a member of the Eastern Cooperative Oncology Group, National Surgical Adjuvant Breast and Bowel Project, Southwest Oncology Group, American Society of Hematology, and American Society of Clinical Oncology. Dr. Kozloff is board certified in hematology and medical oncology.

Dr Mark Kozloff BIO

Edward S. Kim, MD

"The Avastin ECOG 4599 trial is an important study in lung cancer treatment development. With Avastin, we saw for the first time a 3-drug regimen of Avastin plus paclitaxel/carboplatin that was superior in survival versus a 2-drug regimen of paclitaxel/carboplatin alone. It was also the first time that a traditional cytotoxic chemotherapy of paclitaxel/carboplatin was paired with a biologic agent and, in fact, showed a survival benefit. This is something that had previously never been proven in NSCLC trials."

Edward S. Kim, MD, is an Assistant Professor in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas, where he is also the Director of Educational Programs and Director of Residency Training in Oncology. He received his medical degree from Northwestern University in Chicago, Illinois. Dr Kim completed his residency in internal medicine at Baylor College of Medicine in Houston, and his medical oncology fellowship at the University of Texas MD Anderson Cancer Center. Dr Kim has served as principal investigator on numerous research projects and grant awards and has authored numerous publications on lung and other cancers.

Dr Ed Kim BIO

Oncologist comments were solicited in Genentech-sponsored interviews. Participating physicians received compensation for participating in the interviews. Opinions expressed herein reflect the professional views of the oncologists. Their opinions are provided for informational purposes only and should not substitute for your independent medical judgment or assessment of the risks and benefits of using Avastin to treat particular patients.

Boxed WARNINGS

  • Gastrointestinal (GI) perforation: Serious and sometimes fatal GI perforation occurs at a higher incidence (up to 2.4%) in Avastin-treated patients compared to controls. Discontinue Avastin for GI perforation

  • Surgery and wound healing complications: The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients. Discontinue in patients with wound dehiscence. Discontinue at least 28 days prior to elective surgery. Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed

  • Hemorrhage: Severe or fatal hemorrhage, hemoptysis, GI bleeding, CNS hemorrhage, and vaginal bleeding are increased in Avastin-treated patients. Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis

Please see full Prescribing Information, including Boxed WARNINGS, for additional safety information.

Avastin plus PC: A standard in the treatment of first-line NSCLC

Indication

Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer in combination with carboplatin and paclitaxel.

Boxed WARNINGS and additional important safety information

  • Gastrointestinal (GI) perforation: Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to controls. The incidences of GI perforation ranged from 0.3% to 2.4% across clinical studies. Discontinue Avastin in patients with GI perforation

  • Surgery and wound healing complications: The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients. Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed. The appropriate interval between termination of Avastin and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined. Discontinue Avastin at least 28 days prior to elective surgery and in patients with wound dehiscence requiring medical intervention

  • Hemorrhage: Severe or fatal hemorrhage, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 1.2% to 4.6%. Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis (≥1/2 tsp of red blood). Discontinue Avastin in patients with serious hemorrhage (ie, requiring medical intervention)

  • Additional serious and sometimes fatal adverse events for which the incidence was increased in the Avastin-treated arm vs control included non-GI fistula formation (≤0.3%), arterial thromboembolic events (grade ≥3, 2.4%), and proteinuria including nephrotic syndrome (<1%). Additional serious adverse events for which the incidence was increased in the Avastin-treated arm vs control included hypertension (grade 3–4, 5%–18%) and reversible posterior leukoencephalopathy syndrome (RPLS) (<0.1%). Infusion reactions with the first dose of Avastin were uncommon (<3%), and severe reactions occurred in 0.2% of patients

  • The most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate were epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis. Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

  • Grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a ≥2% higher incidence in Avastin-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thrombus/embolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)

Please see full Prescribing Information, including Boxed WARNINGS for additional safety information.

Next: Undifferentiated NSCLC, Not Otherwise Specified

References
  1. Breathnach OS, Freidlin B, Conley B, et al. J Clin Oncol. 2001;19:1734-1742.
  2. Food and Drug Administration. Approved Oncology Drugs with Approved Indications. http://www.accessdata.fda.gov/scripts/cder/onctools/druglist.cfm. Accessed August 20, 2009.
  3. Avastin Prescribing Information, Genentech, Inc. July 2009.