Efficacy in NSCLC

Safety profile of Avastin in first-line NSCLC

A positive benefit-risk ratio in NSCLC with Avastin plus PC

The safety profile of Avastin in combination with PC was demonstrated in Study E4599.1

Avastin plus PC (first-line NSCLC)1

Selected grade 3–5 adverse events*
(≥2% higher incidence in the Avastin plus PC arm)

  • *NCI-CTC (Version 2.0) grade 3–5 nonhematologic and grade 4 and 5 hematologic adverse events.2

  • GI perforation: in Study E4599, 4 of 427 (0.9%) patients receiving Avastin plus PC developed GI perforation. There were no events reported in the PC alone arm (see Boxed WARNINGS in full Prescribing Information)1

  • Hemorrhage: in Study E4599, severe or fatal hemorrhages, including hemoptysis, GI bleeding, CNS hemorrhage, epistaxis, hematemesis, and vaginal bleeding, occurred in 4.7% of NSCLC patients receiving Avastin plus PC compared with 1.1% of control patients (see Boxed WARNINGS in full Prescribing Information)1

  • Arterial thromboembolic events: the incidence of ATEs was increased in NSCLC patients receiving Avastin plus PC in Study E4599 (3.0% vs 1.4% for PC alone patients); 5 events were fatal in the Avastin plus PC arm compared with 1 event in the PC alone arm1

  • Neutropenia and infection: increased rates of severe neutropenia, febrile neutropenia, and infection with severe neutropenia (including some fatalities) have been observed in patients treated with myelosuppressive chemotherapy plus Avastin1

Patient selection and the risk of hemoptysis

Based on a case-control analysis of the Phase II study (Study AVF0757g) as well as findings from an early stage of Study E4599, certain patients were excluded from the Phase III trial.1

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: Dosing and Administration

References
  1. Avastin Prescribing Information. Genentech, Inc. July 2009.
  2. National Cancer Institute. Cancer Therapy Evaluation Program. Common toxicity criteria for adverse events, version 2.0. http://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. Accessed August 20, 2009.