Avastin® (bevacizumab) solution for intravenous infusion in combination with paclitaxel and cisplatin or paclitaxel and topotecan is indicated for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix.
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 3.2% 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 0.4% to 6.9%
— 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
— GI fistulae (up to 2% in metastatic colorectal cancer and ovarian cancer patients)
— Non-GI fistulae (<1% in trials across various indications; 1.8% in a cervical cancer trial)
— 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
— GI-vaginal fistulae occurred in 8.3% of patients in a cervical cancer trial
— Venous thromboembolism (grade 3–4, up to 10.6%) in patients with persistent, recurrent, or metastatic cervical cancer treated with Avastin
— Hypertension (grade 3–4, 5%–18%)
— Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
• 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
Pregnancy warning
• Based on the mechanism of action and animal studies, Avastin may cause fetal harm
• Advise female patients that Avastin may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
• Advise females of reproductive potential to use effective contraception during treatment with Avastin and for 6 months after the last dose of Avastin
• Advise nursing women that breastfeeding is not recommended during treatment with Avastin
• Avastin may impair fertility
Most common adverse events
• Across indications, 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
Indication-specific adverse events
• In CC, grade 3 or 4 adverse reactions in Study GOG 240, occurring at a higher incidence (≥2%) in 218 patients receiving chemotherapy plus Avastin compared to 222 patients receiving chemotherapy alone, were abdominal pain (11.9% vs 9.9%), diarrhea (5.5% vs 2.7%), anal fistula (3.7% vs 0%), proctalgia (2.8% vs 0%), urinary tract infection (8.3% vs 6.3%), cellulitis (3.2% vs 0.5%), fatigue (14.2% vs 9.9%), hypertension (11.5% vs 0.5%), thrombosis (8.3% vs 2.7%), hypokalemia (7.3% vs 4.5%), hyponatremia (3.7% vs 1.4%), dehydration (4.1% vs 0.5%), neutropenia (7.8% vs 4.1%), lymphopenia (6.0% vs 3.2%), back pain (5.5% vs 3.2%), and pelvic pain (5.5% vs 1.4%). There were no grade 5 adverse reactions occurring at a higher incidence (≥2%) in patients receiving chemotherapy plus Avastin compared to patients receiving chemotherapy alone
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.
CC=persistent, recurrent, or metastatic cervical cancer.
AVY/101615/0066
advanced cervical cancer:
Median OS
16.8
months
(vs 12.9 months with chemotherapy alone)1✱
ORR
45%
(vs 34% with chemotherapy alone)1†
view the GOG 240 study overview
view safety profile
including Boxed WARNINGS, for
additional important safety information.
1. Avastin Prescribing Information. Genentech, Inc. December 2015.
OS=overall survival; ORR=overall response rate; GOG=Gynecologic Oncology Group; HR=hazard ratio; CI=confidence interval.
✱HR=0.74 (95% CI, 0.58–0.94), P=0.0132.
†95% CI, 39–52.
Avastin® (bevacizumab) solution for intravenous infusion in combination with paclitaxel and cisplatin or paclitaxel and topotecan is indicated for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix.
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 3.2% 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 0.4% to 6.9%
— 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
— GI fistulae (up to 2% in metastatic colorectal cancer and ovarian cancer patients)
— Non-GI fistulae (<1% in trials across various indications; 1.8% in a cervical cancer trial)
— 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
— GI-vaginal fistulae occurred in 8.3% of patients in a cervical cancer trial
— Venous thromboembolism (grade 3–4, up to 10.6%) in patients with persistent, recurrent, or metastatic cervical cancer treated with Avastin
— Hypertension (grade 3–4, 5%–18%)
— Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
• 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
Pregnancy warning
• Based on the mechanism of action and animal studies, Avastin may cause fetal harm
• Advise female patients that Avastin may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
• Advise females of reproductive potential to use effective contraception during treatment with Avastin and for 6 months after the last dose of Avastin
• Advise nursing women that breastfeeding is not recommended during treatment with Avastin
• Avastin may impair fertility
Most common adverse events
• Across indications, 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
Indication-specific adverse events
• In CC, grade 3 or 4 adverse reactions in Study GOG 240, occurring at a higher incidence (≥2%) in 218 patients receiving chemotherapy plus Avastin compared to 222 patients receiving chemotherapy alone, were abdominal pain (11.9% vs 9.9%), diarrhea (5.5% vs 2.7%), anal fistula (3.7% vs 0%), proctalgia (2.8% vs 0%), urinary tract infection (8.3% vs 6.3%), cellulitis (3.2% vs 0.5%), fatigue (14.2% vs 9.9%), hypertension (11.5% vs 0.5%), thrombosis (8.3% vs 2.7%), hypokalemia (7.3% vs 4.5%), hyponatremia (3.7% vs 1.4%), dehydration (4.1% vs 0.5%), neutropenia (7.8% vs 4.1%), lymphopenia (6.0% vs 3.2%), back pain (5.5% vs 3.2%), and pelvic pain (5.5% vs 1.4%). There were no grade 5 adverse reactions occurring at a higher incidence (≥2%) in patients receiving chemotherapy plus Avastin compared to patients receiving chemotherapy alone
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.
CC=persistent, recurrent, or metastatic cervical cancer.
AVY/101615/0066