Oncologists Speak on Avastin

Undifferentiated NSCLC, not otherwise specified (NOS): Comments from leading oncologists

Mark F. Kozloff, MD

"If it’s a ‘non-small cell unspecified,’ to me that still means they’re eligible for Avastin. Plus, patients with undifferentiated NSCLC, not otherwise specified (NOS), were included in E4599, and they were not at any greater risk for pulmonary hemorrhage."

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

Ronald B. Natale, MD

"Patients with 'undifferentiated NSCLC' or 'NSCLC not otherwise specified' were also included in ECOG 4599. In fact, ECOG 4599 included patients with adenocarcinoma of the lung, large cell undifferentiated carcinoma of the lung, poorly differentiated or undifferentiated carcinoma, and carcinoma not otherwise specified. Those patients with NOS histology were not at any greater risk for pulmonary hemorrhage.."

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

Edward S. Kim, MD

"If the pathology comes as an ‘NSCLC NOS,’ then that patient is eligible for Avastin treatment….This encompasses a significant number of patients, around 20% in E4599. But it doesn’t seem like these particular patients are at increased risk."

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.

The full range of non-squamous NSCLC histologies was included in Study E45991

In a retrospective analysis of Study E4599, patients with tumor histology of undifferentiated NSCLC, not otherwise specified, did not appear to experience increased risk of pulmonary hemorrhage2*

  • *Analysis performed by an external, independent adjudication panel.
  • †PH=Pulmonary hemorrhage.
  • ‡6 cases were identified as early-onset PH (<150 days from the start of treatment) without additional complicating factors.
  • §NR=Not reported.

Important safety information—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).

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: The Evidence-Based Dose

References
  1. Cohen MH, Gootenberg J, Keegan P, Pazdur R. Oncologist. 2007;12:713-718.
  2. Data on file. Genentech, Inc.