X

The link you have selected will take you away from this site to one that is not owned or controlled by Genentech, Inc. Genentech, Inc. makes no representation as to the accuracy of the information contained on sites we do not own or control. Genentech does not recommend and does not endorse the content on any third-party websites. Your use of third-party websites is at your own risk and subject to the terms and conditions of use for such sites.

Proceed Cancel
E-mail This Page
X

Your e-mail has been sent!

Ok
X

Please acknowledge that you have read the below Important Safety Information by clicking the box at the bottom of the screen.

Indication

Indications

Metastatic Renal Cell Carcinoma (mRCC)
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

Glioblastoma (GBM)
Avastin is indicated for the treatment of glioblastoma as a single agent for adult patients with progressive disease following prior therapy. The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin.

Non–Squamous Non–Small Cell Lung Cancer (NSCLC)
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.

Metastatic Colorectal Cancer (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.
Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

Indications

Metastatic Renal Cell Carcinoma (mRCC)
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

Non–Squamous Non–Small Cell Lung Cancer (NSCLC)
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.

Metastatic Colorectal Cancer (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.

Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

Boxed WARNINGS

  • 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 healing complications 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 adverse events

  • Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs control included
    • Non-GI fistula formation (≤0.3%)
    • Arterial thromboembolic events (grade ≥3, 2.6%)
    • Proteinuria (nephrotic syndrome, <1%)
  • Additional serious adverse events with increased incidence in the Avastin-treated arm vs control included
    • Hypertension (grade 3–4, 5%–18%)
    • 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
  • Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin

Most common adverse events

  • Across all studies, 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
     
    Exfoliative dermatitis
     
  • Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

Pregnancy warning

  • Avastin may impair fertility
  • Based on animal data, Avastin may cause fetal harm
  • Advise patients of the potential risk to the fetus during and following Avastin and the need to continue adequate contraception for at least 6 months following the last dose of Avastin
  • For nursing mothers, discontinue nursing or Avastin, taking into account the importance of Avastin to the mother

Indication-specific adverse events

  • In mRCC, the most common grade 3–5 adverse events in AVOREN, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and hemorrhage (3% vs 0.3%)
  • In GBM Study AVF3708g, in patients receiving Avastin alone, the most frequently reported adverse events were infection (55%), fatigue (45%), headache (37%), hypertension (30%), epistaxis (19%), and diarrhea (21%). Of these, the incidence of grade ≥3 adverse events was infection (10%), fatigue (4%), headache (4%), hypertension (8%), and diarrhea (1%). Two deaths were possibly related to Avastin: 1 retroperitoneal hemorrhage and 1 neutropenic infection
  • In GBM patients receiving Avastin alone or Avastin plus irinotecan,a the incidences of Avastin-related adverse events (grade 1–4) were bleeding/hemorrhage (40%), epistaxis (26%), CNS hemorrhage (5%), hypertension (32%), venous thromboembolic events (8%), arterial thromboembolic events (6%), wound healing complications (6%), proteinuria (4%), GI perforation (2%), and RPLS (1%). The incidences of grade 3–5 events in these 163 patients were bleeding/hemorrhage (2%), CNS hemorrhage (1%), hypertension (5%), venous thromboembolic events (7%), arterial thromboembolic events (3%), wound healing complications (3%), proteinuria (1%), and GI perforation (2%). Intracranial hemorrhage occurred in 8 of 163 patients; 2 patients had grade 3–4 hemorrhage
  • In NSCLC, 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%)
  • 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%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study
  • When continued beyond first progression in MCRC, no new safety signals were observed in Study ML18147 when Avastin was administered in second-line MCRC patients who progressed on an Avastin containing regimen in first-line MCRC. The safety data was consistent with the known safety profile established in first- and second-line MCRC

aAvastin is not approved for use in combination with irinotecan.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Genentech at (888) 835-2555.

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

By clicking this box below, I verify that I have read this Important Safety Information and that I am a U.S. Health Care Professional.

I Agree
For Patients & Caregivers For US Healthcare Professionals Only

Receive additional information

Register Now!

Unsubscribe

Manage Your Communications

  X

Boxed WARNINGS

  • 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 healing complications 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 adverse events

  • Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs control included
    • Non-GI fistula formation (≤0.3%)
    • Arterial thromboembolic events (grade ≥3, 2.6%)
    • Proteinuria (nephrotic syndrome, <1%)
  • Additional serious adverse events with increased incidence in the Avastin-treated arm vs control included
    • Hypertension (grade 3–4, 5%–18%)
    • 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
  • Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin

Most common adverse events

  • Across all studies, 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
     
    Exfoliative dermatitis
     
  • Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

Pregnancy warning

  • Avastin may impair fertility
  • Based on animal data, Avastin may cause fetal harm
  • Advise patients of the potential risk to the fetus during and following Avastin and the need to continue adequate contraception for at least 6 months following the last dose of Avastin
  • For nursing mothers, discontinue nursing or Avastin, taking into account the importance of Avastin to the mother

Indication-specific adverse events

  • In mRCC, the most common grade 3–5 adverse events in AVOREN, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and hemorrhage (3% vs 0.3%)
  • In GBM Study AVF3708g, in patients receiving Avastin alone, the most frequently reported adverse events were infection (55%), fatigue (45%), headache (37%), hypertension (30%), epistaxis (19%), and diarrhea (21%). Of these, the incidence of grade ≥3 adverse events was infection (10%), fatigue (4%), headache (4%), hypertension (8%), and diarrhea (1%). Two deaths were possibly related to Avastin: 1 retroperitoneal hemorrhage and 1 neutropenic infection
  • In GBM patients receiving Avastin alone or Avastin plus irinotecan,a the incidences of Avastin-related adverse events (grade 1–4) were bleeding/hemorrhage (40%), epistaxis (26%), CNS hemorrhage (5%), hypertension (32%), venous thromboembolic events (8%), arterial thromboembolic events (6%), wound healing complications (6%), proteinuria (4%), GI perforation (2%), and RPLS (1%). The incidences of grade 3–5 events in these 163 patients were bleeding/hemorrhage (2%), CNS hemorrhage (1%), hypertension (5%), venous thromboembolic events (7%), arterial thromboembolic events (3%), wound healing complications (3%), proteinuria (1%), and GI perforation (2%). Intracranial hemorrhage occurred in 8 of 163 patients; 2 patients had grade 3–4 hemorrhage
  • In NSCLC, 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%)
  • 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%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study
  • When continued beyond first progression in MCRC, no new safety signals were observed in Study ML18147 when Avastin was administered in second-line MCRC patients who progressed on an Avastin containing regimen in first-line MCRC. The safety data was consistent with the known safety profile established in first- and second-line MCRC

aAvastin is not approved for use in combination with irinotecan.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Genentech at (888) 835-2555.

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

Important Safety Information

Avastin and Metastatic Colorectal Cancer (MCRC)

Indications

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.

Avastin in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

NOW APPROVED: Avastin continued beyond first progression in MCRC1

Proven OS benefits with Avastin in the first line and when continued beyond first progression1,2

FDA-approved Prescribing Information for the duration of Avastin treatment First-line MCRC: Start with Avastin
OS=overall survival.

Important treatment considerations—Dose modifications

  • 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)
    • 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

arrow upIn combination with common chemotherapy regimens: Continuing to build a foundation of OS

Avastin is the only FDA-approved biologic proven to increase OS in 3 large Phase III trials in MCRC1

Avastin Phase III trials in MCRC
IFL=5-fluorouracil (5-FU)/leucovorin (LV)/irinotecan; FOLFOX4=5-FU/LV/oxaliplatin.
*Chemotherapy combinations included both irinotecan- and oxaliplatin-containing regimens.1
Additional safety data collected

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

arrow upAvastin is the only FDA-approved biologic that offers a significant survival benefit with confidence based on1:

Evidence across 5-FU–based chemotherapy regimens1,7

Proven OS Benefits

Inclusion in the NCCN guidelines8

  • Bevacizumab is the only biologic that is NCCN recommended through first- and second-line MCRC8
  • Bevacizumab is NCCN recommended across first- and second-line MCRC in combination with multiple fluoropyrimidine-based chemotherapy backbones, including oxaliplatin- and irinotecan-containing regimens8
Additional safety data collected
NCCN=National Comprehensive Cancer Network; FOLFIRI=5-FU/LV/irinotecan; IV=intravenous;
CapeOX=capecitabine/oxaliplatin.

arrow up Only Avastin has proven OS and PFS benefits in:

First-line Study 2107: Treatment-naive patients with MCRC1,6,7

Chart: Median OS: 20.3 vs 15.6 months

HR=hazard ratio; CI=confidence interval.
  • 4.4-month increase in median progression-free survival (PFS) with Avastin plus IFL: 10.6 vs 6.2 months with placebo plus IFL (HR=0.54 [95% CI, 0.45–0.66], P<0.001)1,6
  • Significant increase in overall response rate (ORR) with Avastin plus IFL: 45% vs 35% with placebo plus IFL (P<0.01)1,7

Second-line Study E3200: Patients who did not receive a first-line Avastin-containing regimen1,6,9

Chart: Median OS: 13.0 vs 10.8 months

  • 2.6-month increase in median PFS with Avastin plus FOLFOX4: 7.3 vs 4.7 months with FOLFOX4 alone (HR=0.61, P<0.0001)9
  • Significant increase in ORR with Avastin plus FOLFOX4: 23% vs 9% with FOLFOX4 alone (P<0.0001)9

Continuation of Avastin Beyond First Progression Study ML18147: Patients who progressed after ≥3 months on a first-line Avastin-containing regimen1,2*

Chart: Median OS: 11.2 vs 9.8 months
  • 1.7-month increase in median PFS beyond first progression with Avastin plus fluoropyrimidine-based chemotherapy: 5.7 vs 4.0 months with fluoropyrimidine-based chemotherapy alone (HR=0.68 [95% CI, 0.59–0.78], P<0.0001)1
  • There was no significant difference in response rate1

Safety profile evaluated in 3 large Phase III trials

arrow upAvastin plus IFL: First-line Study 2107
Selected grade 3–4 AEs (≥2% higher incidence in the Avastin arm)1

Chart: NCI-CTC grade 3–4 events at incidence ≥2

AEs=adverse events; NCI-CTC=National Cancer Institute Common Toxicity Criteria.
†
Central laboratories were collected on days 1 and 21 of each cycle. Neutrophil counts were available in 303 patients receiving placebo plus IFL and 276 patients receiving Avastin plus IFL.1

Avastin plus FOLFOX4: Second-line Study E3200
Selected grade 3–5 AEs (≥2% higher incidence in the Avastin arm)1‡

Chart: NCI-CTC grade 3–5 (nonhematologic) and grade 4–5 (hematologic) events

‡
These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study.1

Avastin plus fluoropyrimidine-based chemotherapy*:
Continuation of Avastin Beyond First Progression Study ML181471

No new safety signals or increased incidences of adverse events were observed in Study ML18147 when Avastin was administered in second-line MCRC patients who progressed on an Avastin containing regimen in first-line MCRC. The safety data is consistent with the known safety profile established in first- and second-line MCRC.

The Continuation of Avastin Beyond First Progression Study ML18147:arrow upThe only Phase III clinical trial to prospectively demonstrate a significant OS benefit in second-line patients previously treated with Avastin, a first-line standard of care1,2

Chart: Chemotherapy options
PD=progressive disease.
  • The Continuation of Avastin Beyond First Progression Study ML18147 was a prospective, randomized, open-label, multinational, controlled Phase III study1
    • Primary endpoint: OS, defined as the time from randomization until death from any cause1
    • Secondary endpoints included PFS and overall response rate2
    • Avastin was administered as a solution for IV infusion at 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks in combination with fluoropyrimidine-based chemotherapy1

The Continuation of Avastin Beyond First Progression Study ML18147: Avastin is the only FDA-approved biologic to prospectively demonstrate proven OS and PFS benefits when continued after a first-line Avastin-containing regimen﹡

1.4-month increase in median OS with Avastin continued beyond first progression1

Chart: Median OS: 11.2 vs 9.8 months

1.7-month increase in median PFS with Avastin continued beyond first progression1,2

Chart: Median PFS: 5.7 vs 4.1 months
  • There was no significant difference in response rate1

Avastin plus fluoropyrimidine-based chemotherapy*:
Continuation of Avastin Beyond First Progression Study ML1814711

No new safety signals or increased incidences of adverse events were observed in Study ML18147 when Avastin was administered in second-line MCRC patients who progressed on an Avastin containing regimen in first-line MCRC. The safety data is consistent with the known safety profile established in first- and second-line MCRC.

FDA-approved Prescribing Information for the duration of Avastin treatment First-line MCRC: Start with Avastin

Proven OS Benefits
Chart: Chemotherapy options
     

Indications

Metastatic Renal Cell Carcinoma (mRCC)
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

Non–Squamous Non–Small Cell Lung Cancer (NSCLC)
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.

Metastatic Colorectal Cancer (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.

Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

Boxed WARNINGS

  • 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 healing complications 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 adverse events

  • Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs control included
    • Non-GI fistula formation (≤0.3%)
    • Arterial thromboembolic events (grade ≥3, 2.6%)
    • Proteinuria (nephrotic syndrome, <1%)
  • Additional serious adverse events with increased incidence in the Avastin-treated arm vs control included
    • Hypertension (grade 3–4, 5%–18%)
    • 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
  • Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin

Most common adverse events

  • Across all studies, 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
     
    Exfoliative dermatitis
     
  • Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

Pregnancy warning

  • Avastin may impair fertility
  • Based on animal data, Avastin may cause fetal harm
  • Advise patients of the potential risk to the fetus during and following Avastin and the need to continue adequate contraception for at least 6 months following the last dose of Avastin
  • For nursing mothers, discontinue nursing or Avastin, taking into account the importance of Avastin to the mother

Indication-specific adverse events

  • 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%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study
  • When continued beyond first progression in MCRC, no new safety signals were observed in Study ML18147 when Avastin was administered in second-line MCRC patients who progressed on an Avastin containing regimen in first-line MCRC. The safety data was consistent with the known safety profile established in first- and second-line MCRC

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Genentech at (888) 835-2555.

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

References:

1.
Avastin Prescribing Information. Genentech, Inc. January 2013.
2.
Bennouna J, Sastre J, Arnold D, et al. Lancet Oncol. 2013;14:29-37.
3.
Grothey A, Sugrue MM, Purdie DM, et al. J Clin Oncol. 2008;26:5326-5334.
4.
Van Cutsem E, Rivera F, Berry S, et al. Ann Oncol. 2009;20:1842-1847.
5.
Cohn AL, Bekaii-Saab TS, Bendell JC, et al. J Clin Oncol. 2010;28:15s (suppl; abstr 3596).
6.
Data on file. Genentech, Inc.
7.
Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342.
8.
The NCCN Colon Cancer Clinical Practice Guidelines in Oncology (Version 1.2013). ©2012 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed October 23, 2012. To view the most recent and complete version of the guidelines, go online to www.nccn.org.
9.
Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544.