MCRC Resources

FAQ

Avastin
Clinical Trial Results
Results From the Pivotal Phase III Trials
Safety Profile
Dosing and Administration
Reimbursement Support and Customer Service
Summary

Avastin

arrow up What is Avastin?

Avastin is a therapeutic advance in the combination treatment of MCRC. Avastin is a recombinant humanized monoclonal antibody to VEGF, a protein that has been identified as one of the most potent and predominant mediators of tumor angiogenesis.1,2

arrow up What is the Avastin indication in MCRC?

Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil–based chemotherapy.

arrow up What therapies contain IV 5-FU?

Therapies that contain IV 5-FU include IFL, FOLFIRI, FOLFOX, and 5-FU/LV chemotherapy regimens.

arrow up What is Avastin contraindicated for?

There are no known contraindications to the use of Avastin.1

Clinical Trial Results

arrow up How was Avastin studied in MCRC?

The clinical benefits of Avastin have been evaluated across several randomized clinical trials and in combination with multiple IV 5-FU–containing regimens, including:

  • First-line in combination with IFL: 923 patients with previously untreated MCRC were evaluated in Study 2107 (a Phase III trial). Patients in the study received placebo plus IFL (Arm 1), Avastin 5 mg/kg IV every 2 weeks (q2w) plus IFL (Arm 2), or Avastin 5 mg/kg IV q2w plus IV 5-FU/LV (Arm 3). As prespecified, Arm 3 was discontinued when the relative safety of Avastin plus IFL was established in an interim analysis. The primary endpoint in this rigorous Phase III trial was OS1-3

  • Second-line in combination with FOLFOX4: 829 patients with previously treated MCRC were evaluated in Study E3200 (a Phase III trial). Patients in the study received FOLFOX4 (Arm 1), Avastin 10 mg/kg IV q2w plus FOLFOX4 (Arm 2), or Avastin 10 mg/kg IV q2w alone (Arm 3). The primary endpoint was overall survival. Patients were previously treated with irinotecan and 5-FU for initial therapy for metastatic disease or as adjuvant therapy1,4

Per MCRC trial protocols, Avastin administration was continued until disease progression or unacceptable toxicity.1,2,5

arrow up What were the clinical trial results with Avastin?

In both first- and second-line MCRC, Avastin-based therapy has consistently demonstrated superior survival results over IV 5-FU–containing chemotherapy alone.

  • In first-line Study 2107, Avastin plus IFL resulted in a 4.7-month (30%) increase in median OS vs IFL alone in previously untreated patients. The survival benefit associated with Avastin was observed early in treatment and persisted throughout the course of the trial. Median duration of Avastin therapy was 40.4 weeks1,2

  • In second-line Study E3200, Avastin plus FOLFOX4 resulted in a 2.2-month (20%) increase in median OS vs FOLFOX4 alone. This is the first treatment to extend median OS beyond 1 year in a Phase III trial for second-line MCRC1,4

Raising the survival standard, as observed in pivotal Phase III trials1,2,4

Avastin Efficacy - Results from randomized clinical trials

  • *Chemotherapy regimens with Avastin-based therapy: Study 2107, IFL; Study E3200, FOLFOX4.
  • †Difference statistically significant. HRs for survival: Study 2107, HR=0.66; Study E3200, HR=0.75.

Avastin-based therapy offers broad and consistent clinical benefits

arrow up What was the effect of Avastin-based therapy on other efficacy endpoints?

Avastin-based therapy resulted in significant increases in PFS and ORR in the pivotal Phase III trials.

Increases in PFS in first- and second-line MCRC1,2,4

Increases in PFS in first- and second-line MCRC

  • ‡P<0.001.
  • §P<0.0001.
  • ||Chemotherapy regimens with Avastin-based therapy: Study 2107, IFL; Study E3200, FOLFOX4.
Increases in ORR in first- and second-line MCRC1,2,4

Increases in ORR in first- and second-line MCRC

  • P<0.01.
  • #P<0.0001.
  • **Chemotherapy regimens with Avastin-based therapy: Study 2107, IFL; Study E3200, FOLFOX4.

arrow up What patient subgroups were analyzed in clinical trials?

In the pivotal Phase III trials, a number of subgroups were analyzed based on patient- and disease-related parameters, including age, sex, race, ECOG performance status, location of primary tumor, prior adjuvant therapy, number of metastatic sites, tumor burden, and prior radiotherapy.1,2,4,5

Safety Profile

arrow up What is the safety profile of Avastin?

The positive benefit-risk ratio of Avastin has been observed in both first- and second-line MCRC.

Avastin plus IFL (first-line MCRC)1
Selected grade 3–4 adverse events

Avastin plus IFL (first-line MCRC). Selected grade 3–4 adverse events

  • ††Difference statistically significant (P<0.01).
  • ‡‡Central laboratories were collected on days 1 and 21 of each cycle. Neutrophil counts are available in 303 patients receiving placebo plus IFL and 276 patients receiving Avastin plus IFL.
Avastin plus FOLFOX4 (second-line MCRC)1
Selected grade 3–5 adverse events

Avastin plus FOLFOX4 (second-line MCRC). Selected grade 3–5 adverse events

  • In second-line MCRC, Avastin 10 mg/kg IV q2w plus FOLFOX4 maintained a safety profile consistent with Avastin 5 mg/kg IV q2w plus IFL in first-line treatment, while significantly extending overall survival1,2,4

arrow up What are the most serious adverse events associated with Avastin?

  • 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

arrow up What are additional serious adverse events?

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.

arrow up What are the most common adverse events associated with Avastin?

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.

arrow up What should I know about hypertension?

Incidence: The incidence of severe hypertension is increased in patients receiving Avastin as compared to controls. Across clinical studies, the incidence of grade 3 or 4 hypertension ranged from 5% to 18%.1

Monitoring: Blood pressure (BP) monitoring should be conducted every 2 to 3 weeks during treatment with Avastin. Patients who develop hypertension may require BP monitoring at more frequent intervals (even if they have discontinued therapy).1

Management: Hypertension should be treated with appropriate anti-hypertensive therapy and BP should be monitored regularly. Avastin should be temporarily suspended in patients with severe hypertension not controlled with medical management and permanently discontinued in patients with hypertensive crisis or hypertensive encephalopathy.1

arrow up What should I know about proteinuria and nephrotic syndrome?

Incidence: The incidence and severity of proteinuria is increased in patients receiving Avastin as compared to controls. Across clinical studies, the incidence of grade 3–4 proteinuria (characterized as >3.5 g/24 hours) ranged up to 3.0% in Avastin-treated patients. Nephrotic syndrome occurred in <1% of patients receiving Avastin in clinical trials, in some instances with fatal outcome.1

Monitoring: Patients should be monitored for the development or worsening of proteinuria with serial urinalysis during Avastin therapy. Patients with 2+ or greater urine dipstick reading should undergo further assessment with a 24-hour urine collection.1

Management: Suspend Avastin administration for ≥2 g of proteinuria/24 hours and resume when proteinuria is <2 g/24 hours. Avastin should be discontinued in patients with nephrotic syndrome. Data from a postmarketing safety study showed poor correlation between UPCR (urine protein/creatinine ratio) and 24 hour urine protein (Pearson Correlation 0.39 [95% CI, 0.17%–0.57%]). Patients with moderate to severe proteinuria based on 24-hour collections should be monitored regularly until improvement and/or resolution is observed. The safety of continued treatment in patients with moderate to severe proteinuria has not been evaluated.1

arrow up What should I know about arterial thromboembolic events (ATEs)?

Serious, sometimes fatal, ATEs including cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and a variety of other ATEs occurred at a higher incidence in patients receiving Avastin compared to those in the control arm. Across indications, the incidence of grade ≥3 ATEs in the Avastin-containing arms was 2.4% compared to 0.7% in the control arms. Among patients receiving Avastin in combination with chemotherapy, the risk of developing ATEs during therapy was increased in patients with a history of arterial thromboembolism, or age greater than 65 years. The safety of resumption of Avastin therapy after resolution of an ATE has not been studied. Discontinue Avastin in patients who experience a severe ATE.

arrow up What should I know about gastrointestinal (GI) perforation?

Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to controls. The incidence of GI perforation ranged from 0.3–2.4% across clinical studies. The typical presentation may include abdominal pain, nausea, emesis, constipation, and fever. Perforation can be complicated by intra-abdominal abscess and fistula formation. The majority of cases occurred within the first 50 days of initiation of Avastin. Discontinue Avastin in patients with GI perforation.

arrow up What should I know about surgery and wound healing complications?

Avasin impairs wound healing in animal models. In clinical trials, administration of Avastin was not allowed until at least 28 days after surgery. In a controlled clinical trial, the incidence of wound healing complications, including serious and fatal complications, in patients with MCRC who underwent surgery during the course of Avastin treatment was 15% and in patients who did not receive Avastin, was 4%.

Avastin should not be initiated for at least 28 days following surgery and until the surgical wound is fully healed. Discontinue Avastin in patients with wound healing complications requiring medical intervention. The appropriate interval between the last dose of Avastin and elective surgery is unknown; however, the half-life of Avastin is estimated to be 20 days (range 11–50 days). Suspend Avastin for at least 28 days prior to elective surgery. Do not administer Avastin until the wound is fully healed.

arrow up What should I know about hemorrhage?

Avastin can result in 2 distinct patterns of bleeding: minor hemorrhage, most commonly grade 1 epistaxis; and serious, and in some cases fatal, hemorrhagic events. Severe or fatal hemorrhage, including hemoptysis, gastrointestinal bleeding, hematemesis, CNS hemorrhage, epistaxis, and vaginal bleeding occurred up to five-fold more frequently in patients receiving Avastin compared to patients receiving only chemotherapy. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 1.2% to 4.6%.

Serious or fatal pulmonary hemorrhage occurred in 4 of 13 (31%) patients with squamous cell histology and 2 of 53 (4%) patients with non-squamous non-small cell lung cancer receiving Avastin and chemotherapy compared to none of the 32 (9%) patients receiving chemotherapy alone.

In clinical studies in non-small cell lung cancer where patients with CNS metastases who completed radiation and surgery more than 4 weeks prior to the start of Avastin were evaluated with serial CNS imaging, symptomatic grade 2 CNS hemorrhage was documented in 1 of 83 Avastin-treated patients (rate 1.2%, 95% CI 0.6%–5.93%).

Intracranial hemorrhage occurred in 8 of 163 patients with previously treated GBM; 2 patients had grade 3–4 hemorrhage.

Do not administer Avastin to patients with recent history of hemoptysis of ≥1/2 tsp of red blood. Discontinue Avastin in patients with hemorrhage.

arrow up What monitoring and laboratory tests are necessary?

BP monitoring should be conducted every 2 to 3 weeks during treatment. Patients who develop hypertension may require BP monitoring at more frequent intervals (even if they have discontinued therapy). Patients should also be monitored for the development or worsening of proteinuria with serial urinalyses. Patients with a 2+ or greater urine dipstick reading should undergo further assessment (24-hour urine collection) and should be monitored regularly until improvement and/or resolution is observed.1

Dosing and Administration

arrow up How should Avastin be dosed and administered?

Avastin, used in combination with IV 5-FU–based chemotherapy, is administered as an IV infusion (5 mg/kg or 10 mg/kg) q2w until disease progression or unacceptable toxicity, per study protocols. The only Avastin dosages proven to provide a survival benefit are 5 mg/kg IV q2w with IFL (studied in first-line MCRC) and 10 mg/kg IV q2w with FOLFOX4 (studied in second-line MCRC).1

Established doses in pivotal Phase III MCRC trials1

Avastin dosing in MCRC clinical trials

  • a5 mg/kg IV q2w dose evaluated in first-line MCRC in combination with IFL.
  • b10 mg/kg IV q2w dose evaluated in second-line MCRC in combination with FOLFOX4.
Important treatment considerations—Women of childbearing potential

Avastin may impair fertility. Prior to initiation of therapy, advise patients of the potential risk of Avastin to the developing fetus. Counsel patients who become pregnant about the possible risks, including hazard to the fetus and/or loss of pregnancy, of both continued treatment and prolonged exposure following discontinuation, keeping in mind the approximate half-life of Avastin (20 days; range 11–50 days). Patients should also be counseled to continue adequate contraception for at least 6 months following the last dose of Avastin. Nursing mothers should be advised to discontinue nursing or Avastin, taking into account the half-life of the product and the importance of Avastin to the mother.

The initial Avastin dose should be delivered over 90 minutes following chemotherapy. If tolerated, the second infusion may be given over 60 minutes. If the 60-minute infusion is tolerated, all subsequent infusions may be given over 30 minutes.1

In preparation for the infusion, withdraw the necessary amount of Avastin to obtain the required dose and dilute in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP. Avastin infusions should not be administered or mixed with dextrose solutions. DO NOT ADMINISTER AS AN IV PUSH OR BOLUS. DO NOT INITIATE AVASTIN UNTIL AT LEAST 28 DAYS FOLLOWING SURGERY AND UNTIL THE SURGICAL WOUND IS FULLY HEALED.1

Infusion reactions with the first dose of Avastin were uncommon (<3%), and severe reactions occurred in 0.2% of patients. Infusion reactions in clinical trials and in postmarketing experience include hypertension, hypertensive crises associated with neurologic signs and symptoms, wheezing, oxygen desaturation, NCI-CTC grade 3 hypersensitivity, chest pain, headaches, rigors, and diaphoresis. Stop infusion if a severe adverse reaction occurs and administer appropriate medical therapy.1

arrow up How should Avastin vials be stored?

Avastin vials must be refrigerated at 2°C–8°C (36°F–46°F) and should be protected from light. Store in the original carton until time of use. DO NOT FREEZE. DO NOT SHAKE.1

arrow up How long should Avastin be continued?

Per MCRC trial protocols, Avastin was continued until disease progression or unacceptable toxicity.2,5

MCRC trial protocols2,5c

MCRC
Avastin Efficacy in Metastatic Colorectal Cancer - MCRC trial protocols

  • cIn first- and second-line MCRC, Avastin is indicated in combination with IV 5-FU–containing chemotherapy.

 

FDA-approved prescribing information for the duration of Avastin treatment

arrow up What are the dose modification recommendations for Avastin?

There are no recommended dose reductions. Discontinue Avastin in patients with gastrointestinal (GI) perforations (GI perforations, fistula formation in the GI tract, intra-abdominal abscess), fistula formation involving an internal organ, wound dehiscence and wound healing complications requiring medical intervention, serious hemorrhage (ie, requiring medical intervention), severe arterial thromboembolic event (ATE), hypertensive crisis or hypertensive encephalopathy, reversible posterior leukoencephalopathy syndrome (RPLS) (symptoms usually resolve or improve within days, although some patients have experienced ongoing neurologic sequelae), and nephrotic syndrome. Temporarily suspend Avastin for at least 4 weeks prior to elective surgery, severe hypertension not controlled with medical management, moderate to severe proteinuria pending further evaluation, and severe infusion reactions. The safety of resumption of Avastin therapy in patients that experienced RPLS, ATE, and moderate to severe proteinuria is unknown.

Reimbursement Support and Customer Service

arrow up What reimbursement support services are available for Avastin?

Genentech provides patient reimbursement support services for Avastin through Avastin Access Solutions. Avastin Access Solutions is committed to providing your patients with timely and appropriate coverage information related to Avastin.

Avastin Access Solutions can assist by answering questions related to reimbursement, providing payer coverage information, investigating policy benefits, consulting on appeals, and providing patient assistance resources.

To contact Avastin Access Solutions, call toll free 1-888-249-4918 Monday through Friday, 6 AM to 5 PM (PST). Messages can be left 24 hours a day. Enrollments can be faxed to 1-888-249-4919. Avastin Access Solutions is also accessible 24 hours a day on the Web at www.AvastinAccessSolutions.com.

arrow up Where can I find additional information about Avastin?

Additional information about Avastin clinical data and resources can be found on Avastin.com. For medical inquires, please call Medical Information/Communications at 1-800-821-8590 between 5 AM and 5 PM (PST). Medical Information Request Forms may also be submitted through the "Contact Us" section of Avastin.com.

Summary

arrow up Avastin plus IV 5-FU–containing chemotherapy: significant survival benefits vs IV 5-FU–containing chemotherapy alone in both first- and second-line MCRC

First-line MCRC1,2:

  • Proven efficacy in combination with IFL vs IFL alone (pivotal Phase III trial, n=813)

    • 4.7-month (30%) increase in median OS (20.3 vs 15.6 months, P<0.001)

    • 4.4-month (71%) increase in median PFS (10.6 vs 6.2 months, P<0.001)

    • Increases in response rate (45% vs 35%, P<0.01) and duration of response (10.4 vs 7.1 months)

Second-line MCRC1,4:

  • Proven efficacy in combination with FOLFOX4 vs FOLFOX4 alone (pivotal Phase III trial, n=577)

    • 2.2-month (20%) increase in median OS (13.0 vs 10.8 months, P=0.001)

    • 3-month (67%) increase in median PFS (7.3 vs 4.7 months, P<0.0001)

    • Significant increase in ORR (23% vs 9%, P<0.0001)

Avastin is approved in combination with all regimens containing IV 5-FU, including 5-FU/LV, IFL, FOLFIRI, and FOLFOX.

Indication

Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil–based chemotherapy.

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

  • In first-line MCRC, the most common grade 3–4 events in Study 2107, which occurred at a ≥2% higher incidence in the Avastin plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)

  • In second-line MCRC, the most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), ileus (4% vs 1%), neuropathy–sensory (17% vs 9%), neurologic–other (5% vs 3%), fatigue (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), hypertension (9% vs 2%), and hemorrhage (5% vs 1%)

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


Indication

Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil–based chemotherapy.

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

  • In first-line MCRC, the most common grade 3–4 events in Study 2107, which occurred at a ≥2% higher incidence in the Avastin plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)

  • In second-line MCRC, the most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), ileus (4% vs 1%), neuropathy–sensory (17% vs 9%), neurologic–other (5% vs 3%), fatigue (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), hypertension (9% vs 2%), and hemorrhage (5% vs 1%)

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

Next: Proteinuria and Hypertension Quick Hit

References
  1. Avastin Prescribing Information, Genentech, Inc. July 2009.
  2. Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342.
  3. Hurwitz HI, Fehrenbacher L, Hainsworth JD, et al. J Clin Oncol. 2005;23:3502-3508.
  4. Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544.
  5. Data on file. Genentech, Inc.