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Ovarian Cancer: Avastin Dosing and Usage

Stage III or IV ovarian cancer (OC) after primary surgery
Avastin, in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, is indicated for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection.

Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (rOC)
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.

Avastin, in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by Avastin as a single agent, is indicated for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

For your patients with stage III or IV ovarian cancer, add Avastin at cycle 2 after primary surgery and continue with single-agent Avastin for up to 22 cycles[1]

FDA-approved Prescribing Information for the duration of Avastin treatment[1] 

Avastin® (bevacizumab) dosing duration in stage III/IV ovarian cancer

q3w=every 3 weeks.

Avastin dosing in psOC and prOC

Avastin has approved dosing for use with chemotherapy in ovarian cancer patients and is administered as a solution for intravenous (IV) infusion at the following dose and schedule[1]

Tumor type Chemotherapy Avastin dose Avastin schedule
psOC Carboplatin and gemcitabine (every 3 weeks for 6 to 10 cycles) 15 mg/kg Every 3 weeks
Carboplatin and paclitaxel (every 3 weeks for 6 to 10 cycles) 15 mg/kg Every 3 weeks
prOC Paclitaxel (every week) 10 mg/kg Every 2 weeks
Pegylated liposomal doxorubicin (every 4 weeks) 10 mg/kg Every 2 weeks
Topotecan (every week) 10 mg/kg Every 2 weeks
Topotecan (every 3 weeks) 15 mg/kg Every 3 weeks

psOC=platinum-sensitive ovarian cancer; prOC=platinum-resistant ovarian cancer.

  • For patients with psOC, Avastin monotherapy may be continued after completion of combination therapy treatment cycles: Avastin 15 mg/kg IV q3w until disease progression or unacceptable toxicity

Duration of Avastin in psOC and prOC

The FDA-approved Prescribing Information addresses the duration of Avastin treatment: Patients should continue treatment until disease progression or unacceptable toxicity.[1]

Important treatment considerations—Women of childbearing potential

  • Avastin increases the risk of ovarian failure and may impair fertility. Inform females of reproductive potential of the risk of ovarian failure prior to the first dose of Avastin
  • Long-term effects of Avastin exposure on fertility are unknown
  • Patients should also use effective contraception during treatment and for 6 months following the last dose of Avastin
  • Nursing mothers should not breastfeed during treatment and for 6 months following their last dose of treatment

Important treatment considerations—dose modifications

No dose reductions for Avastin are recommended.

Dose Modifications for Adverse Reactions 

Adverse reaction Severity Dosage modification
Gastrointestinal perforation and fistulae
  • Gastrointestinal perforation, any grade
  • Tracheoesophageal fistula, any grade
  • Fistula, Grade 4
  • Fistula formation involving any internal organ
Discontinue Avastin
Wound healing complications Any Withhold Avastin until adequate wound healing. The safety of resumption of Avastin after resolution of wound healing complications has not been established.
Necrotizing fasciitis Discontinue Avastin
Hemorrhage Grade 3 or 4 Discontinue Avastin
Recent history of hemoptysis of ½ teaspoon (2.5 mL) or more Withhold Avastin
Thromboembolic events
  • Arterial thromboembolism, severe
  • Venous thromboembolism, Grade 4
Discontinue Avastin
Hypertension
  • Hypertensive crisis
  • Hypertensive encephalopathy
Discontinue Avastin
Hypertension, severe Withhold Avastin if not controlled with medical management; resume once controlled
Posterior reversible encephalopathy syndrome (PRES) Any Discontinue Avastin
Renal toxicity and proteinuria Nephrotic syndrome Discontinue Avastin
Proteinuria greater than or equal to 2 grams per 24 hours in absence of nephrotic syndrome
Withhold Avastin until proteinuria less than 2 grams per 24 hours
Infusion-related reaction Severe Discontinue Avastin
Clinically significant Interrupt infusion; resume at a decreased rate of infusion after symptoms resolve
Mild, clinically insignificant Decrease infusion rate
Congestive heart failure Any Discontinue Avastin

Important Safety Information & Indication

Indication

Ovarian Cancer (OC)

Avastin, in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, is indicated for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection.

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.

Avastin, in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by Avastin as a single agent, is indicated for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal 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 Stage III or IV OC after primary surgery, 608 patients received CP+Avastin→Avastin, 607 patients received CP+Avastin→PBO, and 602 patients received CP+PBO→PBO. Grade 3–4 adverse reactions occurring at a higher incidence (≥2%) in either of the Avastin arms vs the chemotherapy only arm were fatigue (CP+Avastin→Avastin, 9%; CP+Avastin→PBO, 6%; CP+PBO→PBO, 6%), hypertension (CP+Avastin→Avastin, 10%; CP+Avastin→PBO, 6%; CP+PBO→PBO, 2%), platelet count decreased (CP+Avastin→Avastin, 21%; CP+Avastin→PBO, 20%; CP+PBO→PBO, 15%), and white blood cell count decreased (CP+Avastin→Avastin, 51%; CP+Avastin→PBO, 53%; CP+PBO→PBO, 50%)

  • In psOC, Grade 3 or 4 adverse reactions in the OCEANS study occurring at a higher incidence (≥2%) in 247 patients receiving Avastin plus carboplatin and gemcitabine (chemotherapy), compared to 233 patients receiving placebo plus chemotherapy, were thrombocytopenia (40% vs 34%), nausea (4% vs 1.3%), fatigue (6% vs 4%), headache (4% vs 0.9%), proteinuria (10% vs 0.4%), dyspnea (4% vs 1.7%), epistaxis (5% vs 0.4%), and hypertension (17% vs 0.9%)

  • In psOC, Grade 3 or 4 adverse reactions in the GOG-0213 study occurring at a higher incidence (≥2%) in 325 patients receiving Avastin plus carboplatin and paclitaxel (chemotherapy), compared to 332 patients receiving chemotherapy alone, were hypertension (11% vs 0.6%), fatigue (8% vs 3%), febrile neutropenia (6% vs 3%), proteinuria (8% vs 0%), abdominal pain (6% vs 0.9%), hyponatremia (4% vs 0.9%), headache (3% vs 0.9%), and pain in extremity (3.4% vs 0%)

  • In prOC, Grade 3–4 adverse reactions in AURELIA 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%)

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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