Cervical Cancer: Avastin Efficacy Data


Avastin® (bevacizumab) is the first biologic regimen to demonstrate overall survival (OS) benefit vs chemotherapy alone in persistent, recurrent, or metastatic cervical cancer (CC). [1]

Avastin plus chemotherapy demonstrated statistically significant OS vs chemotherapy alone in CC in the GOG-0240 study [1]

GOG-0240 study: OS results in CC patients

  • 3.9-month increase in median OS: 16.8 months with Avastin plus chemotherapy vs 12.9 months with chemotherapy alone [1]
    • Hazard ratio (HR)=0.74 (95% confidence interval [CI], 0.58–0.94); P=0.0132 [1]
Avastin® (bevacizumab) GOG 240 Clinical Study Overall Survival Results in Cervical Cancer Patients

Chemotherapy included either cisplatin/paclitaxel or topotecan/paclitaxel.
GOG=Gynecologic Oncology Group.

GOG-0240 study: Efficacy data overview [1]

Endpoint

 

Avastin + chemotherapy

Chemotherapy alone

HR
(95% CI)

value

 

Number of
patients

227

225

 

 

Primary

OS
(median)

16.8 months

12.9 months

0.74
(0.58–0.94)

0.0132

Secondary

ORR

45%
(95% CI, 39–52)

34%
(95% CI, 28–40)

 

Chemotherapy included either cisplatin/paclitaxel or topotecan/paclitaxel.
ORR=overall response rate.

Avastin plus chemotherapy demonstrated increases in OS and ORR [1]:

  • A 30% increase in median OS vs chemotherapy alone (16.8 vs 12.9 months)
  • A 26% reduction in the risk of death vs chemotherapy alone

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

OS results by chemotherapy regimen (platinum doublet vs nonplatinum doublet) were also evaluated in the GOG-0240 study, regardless of combination with Avastin [1]

Chemotherapy analysis of the GOG-0240 study: platinum doublet vs nonplatinum doublet

 

Topotecan/paclitaxel
+/- Avastin
(n=223)

Cisplatin/paclitaxel
+/- Avastin
(n=229)

Median OS (months)

13.3

15.5

Hazard ratio

1.15 (95% CI, 0.91–1.46)
P=0.23

  • HR for OS with Avastin plus cisplatin/paclitaxel vs cisplatin/paclitaxel alone was 0.72 (95% CI, 0.51–1.02)
  • HR for OS with Avastin plus topotecan/paclitaxel vs topotecan/paclitaxel alone was 0.76 (95% CI, 0.55–1.06)

The GOG-0240 study evaluated Avastin plus chemotherapy vs chemotherapy alone for CC [1,45]

Avastin® (bevacizumab) GOG 240 Study Avastin with Chemotherapy Versus Chemotherapy Alone for Cervical Cancer Results
  • The GOG-0240 study was a randomized, active-controlled, multicenter study conducted in the US and Spain through the Gynecologic Oncology Group (GOG) and the Spanish Research Group for Ovarian Cancer, and was sponsored by the National Cancer Institute
  • Primary endpoint of the GOG-0240 study was OS, with secondary endpoint ORR

The GOG-0240 study included a diverse population of women with CC [1]
 

Patient characteristics

All patients randomized
at baseline
(N=452)

Median age (range)

48 years (20–85)

Race

Caucasian

Non-Caucasian

 

78%

22%

Prior radiation

80%

Prior chemotherapy concurrent with radiation

74%

Platinum-free interval <6 months

32%

GOG performance status

0

1

 

58%

42%

Demographic and disease characteristics were balanced across arms

Chemotherapy included either cisplatin/paclitaxel or topotecan/paclitaxel. 

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

Indications

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.

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to patients treated with chemotherapy
    • The incidence of GI perforation ranged from 0.3% to 3% 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
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue 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. In clinical studies, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 0.4% to 7%
    • Do not administer Avastin to patients with serious hemorrhage or a recent history of hemoptysis (≥1/2 tsp of red blood)
    • Discontinue Avastin in patients who develop grade 3-4 hemorrhage

Additional serious adverse events

  • Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
    • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
    • Arterial thromboembolic events (grade ≥3, 5%, highest in patients with GBM)
    • Renal injury and proteinuria
      • Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
      • Nephrotic syndrome (<1%)
  • Additional serious adverse events 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) (1%)
  • Infusion reactions with the first dose of Avastin occurred in <3% of patients, 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 and for 6 months following their last dose of treatment
  • Avastin may impair fertility

Most common adverse events

  • 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
— Rectal 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 events

  • 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, including Boxed WARNINGS, for additional important safety information.