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Cervical Cancer: Avastin Safety Profile

Persistent, recurrent, or metastatic cervical cancer (CC)
Avastin, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Safety profile of Avastin in CC was evaluated in the GOG-0240 study: Avastin plus chemotherapy vs chemotherapy alone

Grade 1–4 adverse reactions observed in the GOG-0240 study (with incidence difference of ≥5% between treatment arms)[1]
 

Adverse reaction Patients (%)
Avastin + chemotherapy
(n=218)
Chemotherapy alone
(n=222)
Metabolism and nutrition disorders    
Decreased appetite 26 19
Hyperglycemia 34 26
Hypomagnesemia 24 15
Weight decreased 21 7
Hyponatremia 19 10
Hypoalbuminemia 16 11
General disorders    
Fatigue 80 75
Edema peripheral 15 22
Infections and infestations    
Urinary tract infection 22 14
Infection 10 5
Vascular disorders    
Hypertension 29 6
Thrombosis 10 3
Nervous system disorders    
Headache 22 13
Dysarthria 8 1
Gastrointestinal disorders    
Stomatitis 15 10
Proctalgia 6 1
Anal fistula 6 0
Blood and lymphatic system disorders    
Neutropenia 12 6
Lymphopenia 12 5
Psychiatric disorders    
Anxiety 17 10
Reproductive system and breast disorders    
Pelvic pain 14 8
Respiratory, thoracic, and mediastinal disorders    
Epistaxis 17 1
Renal and urinary disorders    
Blood creatinine increased 16 10
Proteinuria 10 3

Chemotherapy included either cisplatin/paclitaxel or topotecan/paclitaxel.

Indication-specific adverse reactions

  • In CC, Grade 3 or 4 adverse reactions in Study GOG-0240, occurring at a higher incidence (≥2%) in 218 patients receiving Avastin plus chemotherapy compared to 222 patients receiving chemotherapy alone, were abdominal pain (12% vs 10%), diarrhea (6% vs 3%), anal fistula (4% vs 0%), proctalgia (3% vs 0%), urinary tract infection (8% vs 6%), cellulitis (3% vs 0.5%), fatigue (14% vs 10%), hypertension (11% vs 0.5%), thrombosis (8% vs 3%), hypokalemia (7% vs 4%), hyponatremia (4% vs 1%), dehydration (4% vs 0.5%), neutropenia (8% vs 4%), lymphopenia (6% vs 3%), back pain (6% vs 3%), and pelvic pain (6% vs 1%) 

Indication

Persistent, recurrent, or metastatic cervical cancer (CC)

Avastin, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Serious adverse reactions (Warnings and Precautions)

  • Serious and sometimes fatal adverse reactions with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
    • Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies
    • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
    • Arterial thromboembolic events (Grade ≥3, 5%, highest in patients with GBM)
    • The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients
    • Hemorrhage (Grade 3–5) ranged from 0.4% to 7% of patients across clinical studies
    • Renal injury and proteinuria
      • Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
      • Nephrotic syndrome (<1%)
  • Additional serious adverse reactions with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
    • Venous thromboembolism (Grade ≥3, 11% seen in GOG-0240)
    • Hypertension (Grade 3–4, 5%–18%)
    • Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
    • Congestive heart failure (CHF): Grade ≥3 left ventricular dysfunction (1%)
  • Infusion-related reactions with the first dose of Avastin occurred in <3% of patients, and severe reactions occurred in 0.4% of patients
  • 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
  • Inform females of reproductive potential of the risk of ovarian failure prior to initiating treatment with Avastin
  • An evaluation for the presence of varices is recommended within 6 months of initiation of Avastin in patients with HCC

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 not to breastfeed during treatment with Avastin and for 6 months following their last dose of treatment
  • Avastin may impair fertility

Most common adverse reactions

  • Across studies, the most common adverse reactions observed in Avastin patients at a rate >10% were:
    • Epistaxis
    • Headache
    • Hypertension
    • Rhinitis
    • Proteinuria
    • Taste alteration
    • Dry skin
    • Hemorrhage
    • Lacrimation disorder
    • Back pain
    • Exfoliative dermatitis

  • Across all studies, Avastin was discontinued in 8% to 22% of patients because of adverse reactions

Indication-specific adverse reactions

  • In CC, Grade 3 or 4 adverse reactions in Study GOG-0240, occurring at a higher incidence (≥2%) in 218 patients receiving Avastin plus chemotherapy compared to 222 patients receiving chemotherapy alone, were abdominal pain (12% vs 10%), diarrhea (6% vs 3%), anal fistula (4% vs 0%), proctalgia (3% vs 0%), urinary tract infection (8% vs 6%), cellulitis (3% vs 0.5%), fatigue (14% vs 10%), hypertension (11% vs 0.5%), thrombosis (8% vs 3%), hypokalemia (7% vs 4%), hyponatremia (4% vs 1%), dehydration (4% vs 0.5%), neutropenia (8% vs 4%), lymphopenia (6% vs 3%), back pain (6% vs 3%), and pelvic pain (6% vs 1%)

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 for additional important safety information.

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    • MMIT Analysis.

      MMIT Analysis.

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