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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.
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 renal cell carcinoma (mRCC)
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.
Persistent, recurrent, or metastatic cervical cancer (CC)
Avastin in combination with paclitaxel and cisplatin or paclitaxel and topotecan is indicated for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix.
Platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (prOC)
Avastin in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens.
- 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
- 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
- Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
- 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
— 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 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 the TML 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
- 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 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 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
- In prOC, grade 3–4 adverse events occurring at a higher incidence (≥2%) in 179 patients receiving Avastin plus chemotherapy compared to 181 patients receiving chemotherapy alone were hypertension (6.7% vs 1.1%) and palmar-plantar erythrodysaesthesia syndrome (4.5% vs 1.7%). There were no grade 5 events occurring at a higher incidence (≥2%) in patients receiving Avastin plus chemotherapy compared to patients receiving chemotherapy alone