Skip To Main Content
Patient & Caregivers Site

Colorectal Cancer (mCRC) Lung Cancer (nsNSCLC) Kidney Cancer (mRCC) Cervical Cancer (CC) Ovarian Cancer (OC) Recurrent Glioblastoma (rGBM)

Prescribing Information

Lung Cancer: Avastin Efficacy Data

First-line non-squamous non-small cell lung cancer (NSCLC)
Avastin, in combination with carboplatin and paclitaxel, is indicated for the first‑line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer.

Study E4599 Results: Avastin plus PC demonstrated superior survival to PC alone in first-line advanced nsNSCLC

In Study E4599, median OS with Avastin plus PC was 12.3 months vs 10.3 months with PC alone (HR=0.80 [95% CI, 0.68–0.94], P=0.013)[1,8]

Avastin® (bevacizumab) Clinical Study E4599 Overall Survival Percentage

nsNSCLC=non-squamous non-small cell lung cancer; PC=paclitaxel + carboplatin; OS=overall survival; HR=hazard ratio; CI=confidence interval.

More than half of Avastin-treated patients were alive at 1 year in Study E4599.[8]

  • Median progression-free survival (PFS) with Avastin plus PC was 6.2 months vs 4.5 months with PC alone (HR=0.66 [95% CI, 0.57–0.77), P<0.001), based on investigator assessment (not independently verified)[1,8]
  • Response rate with Avastin plus PC was 35% vs 15% with PC alone (P<0.001), based on investigator assessment (not independently verified)[8]

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.

Study E4599: OS in the intent-to-treat population[1,8]

Study E4599 was the first prospective Phase III randomized clinical trial of an FDA-approved biologic in first-line advanced non-squamous NSCLC to demonstrate statistically significant improvement in OS (>12 months), its primary endpoint, in an intent-to-treat population.[1,8]

The intent-to-treat population included all patients randomized before start of treatment. The results of Study E4599 included both progressors and non-progressors.[8]

Use of bevacizumab (Avastin) in the first line increases availability of second-line therapeutic options in the treatment of nsNSCLC[9]

In nsNSCLC, approval of Avastin is only in first line and as treatment to progression or unacceptable toxicity[1]

1L metastatic non-squamous NSCLC Treatment Algorithm

Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2019. © 2019 National Comprehensive Cancer Network, Inc. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application in any way. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.[9]
*Chemotherapy given for up to 6 cycles.[1,8]
†PS 0-1 non-squamous NSCLC and no recent history of hemoptysis. Bevacizumab should not be given as a single agent unless as maintenance if initially used with chemotherapy. Any regimen with a high risk of thrombocytopenia and the potential risk of bleeding should be used with caution in combination with bevacizumab.[9]

Study E4599 was a large Phase III trial that investigated a broad range of over 850 patients with advanced nsNSCLC[8,10,11] 

Patients studied in ECOG Study E4599 included:
  • First-line, locally advanced, metastatic or recurrent NSCLC
  • All predominantly non-squamous histologies
    • Adenocarcinoma
    • Large cell tumors
    • Bronchioloalveolar carcinoma
    • Undifferentiated NSCLC, not otherwise specified
  • Centrally located tumors
  • ECOG PS 0–1

ECOG=Eastern Cooperative Oncology Group.

  • Study E4599 was a Phase III, randomized, active-controlled, open-label, multicenter study that compared Avastin plus PC versus PC alone in patients with locally advanced, metastatic, or recurrent nsNSCLC[1,8]

Histologies in Study E4599[3,8,11] 

1L metastatic non-squamous NSCLC in Study E4599 Chart

One patient in the Avastin plus PC arm was missing in the evaluation of histologies.

The intent-to-treat population included all patients randomized before start of treatment. The results of Study E4599 included both progressors and non-progressors. Baseline demographics and patient characteristics were evaluated for the intent-to-treat population. Histology information was not available for 1 patient in the Avastin + PC arm.[3,8,11] 

The WARNINGS AND PRECAUTIONS section of the Avastin full Prescribing Information states:
In clinical studies in NSCLC where patients with CNS metastases who completed radiation and surgery more than 4 weeks prior to the start of Avastin were evaluated with serial CNS imaging, symptomatic grade 2 CNS hemorrhage was documented in 1 of 83 Avastin-treated patients (rate 1.2%; 95% CI, 0.06%–5.93%). [1]

CNS=central nervous system.

View the Study E4599 publication by Sandler et al

Important Safety Information & Indication

Indication

First-line non-squamous non-small cell lung cancer (NSCLC)

Avastin, in combination with carboplatin and paclitaxel, is indicated for the first‑line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung 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 NSCLC, Grade 3–5 (nonhematologic) and Grade 4–5 (hematologic) adverse reactions 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 thromboembolism (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%)

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. 2022.

      Avastin Prescribing Information. Genentech, Inc. 2022.

    • 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.