Skip To Main Content

Cervical Cancer: Avastin Efficacy Data

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.

Avastin plus chemotherapy demonstrated statistically significant overall survival (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
 
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.

Select Important Safety Information

The Warnings and Precautions for Avastin include gastrointestinal perforation and fistulae, surgery and wound healing complications, hemorrhage, arterial thromboembolic events, venous thromboembolic events, hypertension, posterior reversible encephalopathy syndrome, renal injury and proteinuria, infusion-related reactions, embryo-fetal toxicity, ovarian failure, and congestive heart failure.

GOG-0240 study: Efficacy data overview[1] 

Endpoint   Avastin + chemotherapy Chemotherapy alone HR (95% CI) P 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

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
HR 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[1,16] 

Avastin® (bevacizumab) GOG-0240 Study Design
  • The GOG-0240 study was a randomized, active-controlled, multicenter study conducted in the US and Spain through GOG and the Spanish Research Group for Ovarian Cancer, and was sponsored by the National Cancer Institute
  • The primary endpoint of the GOG-0240 study was OS, and the secondary endpoint was 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 PS
0
1

58%
42%
Demographic and disease characteristics were balanced across arms

Chemotherapy included either cisplatin/paclitaxel or topotecan/paclitaxel. 

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.

    • Avastin Prescribing Information. Genentech, Inc. 2020.

      Avastin Prescribing Information. Genentech, Inc. 2020.

    • Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342. PMID: 15175435  

      Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342. PMID: 15175435  

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

    • Bennouna J, Sastre J, Arnold D, et al. Lancet Oncol. 2013;14:29-37.  

      Bennouna J, Sastre J, Arnold D, et al. Lancet Oncol. 2013;14:29-37.  

    • Österlund P, Alonso-Orduña V, Schlichting C, et al. Poster presented at: European Society for Medical Oncology Meeting; September 28-October 2, 2012; Vienna, Austria.

      Österlund P, Alonso-Orduña V, Schlichting C, et al. Poster presented at: European Society for Medical Oncology Meeting; September 28-October 2, 2012; Vienna, Austria.

    • Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544. PMID: 17442997

      Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544. PMID: 17442997

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Sandler A, Gray R, Perry MC, et al. N Engl J Med. 2006;355:2542-2550. PMID: 17167137  

      Sandler A, Gray R, Perry MC, et al. N Engl J Med. 2006;355:2542-2550. PMID: 17167137  

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Sandler AB, Schiller JH, Gray R, et al. J Clin Oncol. 2009;27:1405-1412.

      Sandler AB, Schiller JH, Gray R, et al. J Clin Oncol. 2009;27:1405-1412.

    • Cohen MH, Gootenberg J, Keegan P, Pazdur R. Oncologist. 2007;12:713-718.

      Cohen MH, Gootenberg J, Keegan P, Pazdur R. Oncologist. 2007;12:713-718.

    • Sandler A, Leon L, Fages S, et al. Poster presented at: World Conference on Lung Cancer; July 3-7, 2011; Amsterdam, The Netherlands.

      Sandler A, Leon L, Fages S, et al. Poster presented at: World Conference on Lung Cancer; July 3-7, 2011; Amsterdam, The Netherlands.

    • Escudier B, Bellmunt J, Negrier S, et al. Slides presented at: Annual Meeting of the American Society of Clinical Oncology; May 29-June 2, 2009; Orlando, FL. 

      Escudier B, Bellmunt J, Negrier S, et al. Slides presented at: Annual Meeting of the American Society of Clinical Oncology; May 29-June 2, 2009; Orlando, FL. 

    • Escudier B, Pluzanska A, Koralewski P, et al. Lancet. 2007;370:2103-2111. PMID: 18156031

      Escudier B, Pluzanska A, Koralewski P, et al. Lancet. 2007;370:2103-2111. PMID: 18156031

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer V.1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer V.1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Tewari KS, Sill MW, Long HJ III, et al. N Engl J Med. 2014;370:734-743 [supplementary appendix appears online].

      Tewari KS, Sill MW, Long HJ III, et al. N Engl J Med. 2014;370:734-743 [supplementary appendix appears online].

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cervical Cancer V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 25, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cervical Cancer V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 25, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Rich JT, Neely JG, Paniello RC, et al. Otolaryngol Head Neck Surg. 2010;143:331-336.

      Rich JT, Neely JG, Paniello RC, et al. Otolaryngol Head Neck Surg. 2010;143:331-336.

    • Burger RA, Brady MF, Bookman MA, et al. N Engl J Med. 2011;365:2473-2483.

      Burger RA, Brady MF, Bookman MA, et al. N Engl J Med. 2011;365:2473-2483.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Aghajanian C, Blank S, Goff B, et al. J Clin Oncol. 2012;30(17):2039-2045.

      Aghajanian C, Blank S, Goff B, et al. J Clin Oncol. 2012;30(17):2039-2045.

    • Aghajanian C, Goff B, Nycum LR, et al. Gynecol Oncol. 2015;139(1):10-16.

      Aghajanian C, Goff B, Nycum LR, et al. Gynecol Oncol. 2015;139(1):10-16.

    • Coleman RL, Brady MF, Herzog TJ, et al. Lancet Oncol. 2013;18(6):779-791.

      Coleman RL, Brady MF, Herzog TJ, et al. Lancet Oncol. 2013;18(6):779-791.

    • Pujade-Lauraine E, Hilpert F, Weber B, et al. J Clin Oncol. 2014;32(13):1302-1308.

      Pujade-Lauraine E, Hilpert F, Weber B, et al. J Clin Oncol. 2014;32(13):1302-1308.

    • Bevacizumab and lomustine for recurrent GBM. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01290939. Updated February 21, 2018. Accessed July 24, 2019.

      Bevacizumab and lomustine for recurrent GBM. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01290939. Updated February 21, 2018. Accessed July 24, 2019.

    • Friedman HS, Prados MD, Wen PY, et al. J Clin Oncol. 2009;27:4733-4740.

      Friedman HS, Prados MD, Wen PY, et al. J Clin Oncol. 2009;27:4733-4740.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027.

      Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027.

    • Bergers G, Benjamin LE. Nat Rev Cancer. 2003;3:401-410.

      Bergers G, Benjamin LE. Nat Rev Cancer. 2003;3:401-410.

    • Folkman J. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. Vol 2. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:2865-2882.

      Folkman J. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. Vol 2. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:2865-2882.

    • Hanrahan V, Currie MJ, Gunningham SP, et al. J Pathol. 2003;200:183-194.

      Hanrahan V, Currie MJ, Gunningham SP, et al. J Pathol. 2003;200:183-194.

    • Rini BI, Small EJ. J Clin Oncol. 2005;23:1028-1043.

      Rini BI, Small EJ. J Clin Oncol. 2005;23:1028-1043.

    • Presta LG, Chen H, O’Connor SJ, et al. Cancer Res. 1997;57:4593-4599.

      Presta LG, Chen H, O’Connor SJ, et al. Cancer Res. 1997;57:4593-4599.

    • Ferrara N. Endocr Rev. 2004;25:581-611.

      Ferrara N. Endocr Rev. 2004;25:581-611.

    • Ferrara N, Hillan KJ, Gerber HP, et al. Nat Rev Drug Discov. 2004;3:391-400.

      Ferrara N, Hillan KJ, Gerber HP, et al. Nat Rev Drug Discov. 2004;3:391-400.

    • O’Connor JPB, Carano RAD, Clamp AR, et al. Clin Cancer Res. 2009;15:6674-6682.

      O’Connor JPB, Carano RAD, Clamp AR, et al. Clin Cancer Res. 2009;15:6674-6682.

    • Tobelem G. Targ Oncol. 2007;2:153-164.

      Tobelem G. Targ Oncol. 2007;2:153-164.

    • Yuan F, Chen Y, Dellian M, et al. Proc Natl Acad Sci U S A. 1996;93:14765-14770.

      Yuan F, Chen Y, Dellian M, et al. Proc Natl Acad Sci U S A. 1996;93:14765-14770.

    • Willett CG, Boucher Y, di Tomaso E, et al. Nat Med. 2004;10:145-147.

      Willett CG, Boucher Y, di Tomaso E, et al. Nat Med. 2004;10:145-147.

    • Lee CG, Heijn M, di Tomaso E, et al. Cancer Res. 2000;60:5565-5570.

      Lee CG, Heijn M, di Tomaso E, et al. Cancer Res. 2000;60:5565-5570.

    • Gerber HP, Ferrara N. Cancer Res. 2005;65:671-680.

      Gerber HP, Ferrara N. Cancer Res. 2005;65:671-680.

    • Yanagisawa M, Yorozu K, Kurasawa M, et al. Anti-Cancer Drugs. 2010;21:687-694.

      Yanagisawa M, Yorozu K, Kurasawa M, et al. Anti-Cancer Drugs. 2010;21:687-694.

    • Borgström P, Hillan KJ, Sriramarao P, et al. Cancer Res. 1996;56:4032-4039.

      Borgström P, Hillan KJ, Sriramarao P, et al. Cancer Res. 1996;56:4032-4039.

    • Borgström P, Bourdon MA, Hillan KJ, et al. Prostate. 1998;35:1-10.

      Borgström P, Bourdon MA, Hillan KJ, et al. Prostate. 1998;35:1-10.

    • Bagri A, Berry L, Gunter B, et al. Clin Cancer Res. 2010;16:3887-3900 [and supplemental appendix].

      Bagri A, Berry L, Gunter B, et al. Clin Cancer Res. 2010;16:3887-3900 [and supplemental appendix].

    • Warren RS, Yuan H, Matli MR, et al. J Clin Invest. 1995;95:1789-1797.

      Warren RS, Yuan H, Matli MR, et al. J Clin Invest. 1995;95:1789-1797.

    • Mabuchi S, Terai Y, Morishige K, et al. Clin Cancer Res. 2008;14:7781-7789.

      Mabuchi S, Terai Y, Morishige K, et al. Clin Cancer Res. 2008;14:7781-7789.

    • Nagy JA, Dvorak AM, Dvorak HF. Annu Rev Pathol. 2007;2:251-275.

      Nagy JA, Dvorak AM, Dvorak HF. Annu Rev Pathol. 2007;2:251-275.

    • Galizia G, Lieto E, Ferraraccio F, et al. Clin Cancer Res. 2004;10:3490-3499.

      Galizia G, Lieto E, Ferraraccio F, et al. Clin Cancer Res. 2004;10:3490-3499.

    • Vosseler S, Mirancea N, Bohlen P, et al. Cancer Res. 2005;65:1294-1305.

      Vosseler S, Mirancea N, Bohlen P, et al. Cancer Res. 2005;65:1294-1305.

    • MMIT Analysis.

      MMIT Analysis.

    • IQVIA Plantrak Corticosteroid Data.

      IQVIA Plantrak Corticosteroid Data.

    • HLI lives database.

      HLI lives database.