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For Patient and Caregivers

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Kidney Cancer: Avastin Dosing and Usage

Metastatic renal cell carcinoma (mRCC)
Avastin, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma.

Avastin dosing in metastatic renal cell carcinoma

In mRCC, Avastin is administered as a solution for intravenous (IV) infusion at the following dose and schedule[1]: 

Tumor type Combination regimen Avastin dose Avastin schedule
mRCC* IFN 10 mg/kg IV Every 2 weeks

IFN=interferon alfa; MIU=million international units.
*10 mg/kg IV dose evaluated in mRCC in combination with IFN. AVOREN protocol allowed for IFN dose escalation (attaining a dose of 9 MIU within the first 2 weeks), reduction, or discontinuation. IFN was discontinued after 52 weeks or earlier.[3,14]

  • 10 mg/kg IV every 2 weeks is the only dose of Avastin proven to increase progression-free survival and objective response rate in mRCC[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

Duration of Avastin in metastatic renal cell carcinoma

Patients were treated until disease progression or unacceptable toxicity.

Clinical benefits have been observed with Avastin given until disease progression or unacceptable toxicity[1,14]

  • Avastin was continued until disease progression or unacceptable toxicity in AVOREN, even if IFN was reduced or discontinued[1,14]
     
Avastin® (bevacizumab) Duration in Metastatic Renal Cell Carcinoma Versus IFN

q2w=every 2 weeks.
†An initial dose of less than 9 MIU was permitted as long as the recommended dose was reached within the first 2 weeks of treatment.[14]

  • IFN was discontinued after a maximum of 52 weeks, but Avastin was continued until disease progression or unacceptable toxicity[1,14]
  • In AVOREN, 31% (105/337) of patients in the Avastin plus IFN arm discontinued IFN after 52 weeks and received Avastin alone thereafter[1,14]
    • 49% (165/337) of patients in the Avastin plus IFN group received IFN dose reduction and 21% (71/337) discontinued IFN prior to 52 weeks[3]
  • Avastin was not dose reduced but was discontinued in 21% (71/337) of patients vs 6% (17/304) discontinuation of placebo in the placebo plus IFN group[3,14]

AVOREN protocol allowed for IFN dose escalation,† reduction, or discontinuation[3,14] 

AVOREN Protocol Allowed for IFN Dose Escalation, Reduction, or Discontinuation

†An initial dose of less than 9 MIU was permitted as long as the recommended dose was reached within the first 2 weeks of treatment.[14]
‡After IFN held, per protocol.

IFN was discontinued in any patient with[3,14]

  • Grade 4 toxicity
  • Grade 3 toxicity that did not resolve to grade ≤1 within 4 weeks while IFN was held
  • Grade 3 toxicity after 2 dose modifications
  • 52 weeks 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
View Avastin dosing across all approved cancer types

Important Safety Information & Indication

Indication

Metastatic renal cell carcinoma (mRCC)

Avastin, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma.

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 mRCC, the most common Grade 3–5 adverse reactions in AVOREN, occurring at a >2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%, including hypertension and hypertensive crisis), and hemorrhage (3% vs 0.3%; including epistaxis, small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, hemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma)

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.