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You are here: Home / Our Medicines / Avastin

Avastin

Avastin is a VEGF inhibitor used to treat a wide range of cancers.

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Please review the Data Sheet before prescribing.

Avastin is a vascular endothelial growth factor (VEGF) inhibitor used to treat a wide range of cancers.

Avastin is a Prescription Medicine, available as 100mg/4mL and 400mg/16mL single-dose vials for intravenous (IV) infusion.

For information on dosage and administration of Avastin, please refer to the Data Sheet on the Medsafe website here.

Medsafe-registered indications1

Metastatic Colorectal Cancer

Avastin in combination with fluoropyrimidine-based chemotherapy is indicated for the treatment of patients with metastatic colorectal cancer.

Advanced and/or metastatic Renal Cell Cancer

Avastin in combination with interferon alfa-2a is indicated for treatment of patients with advanced and/or metastatic renal cell cancer.

Advanced, metastatic or recurrent 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 advanced, recurrent or metastatic NSCLC.

Metastatic Breast Cancer

Avastin in combination with paclitaxel is indicated for the first-line treatment of metastatic breast cancer in patients in whom an anthracycline-based therapy is contraindicated.

Relapsed high grade malignant glioma

Avastin as a single agent is indicated for the treatment of patients with high grade relapsed malignant glioma.

Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Avastin in combination with carboplatin and paclitaxel is indicated for first-line treatment of patients with advanced (FIGO stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Avastin in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin is indicated for the treatment of patients with recurrent, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received no more than two prior chemotherapy regimens, and have not received any prior anti-angiogenic therapy including bevacizumab.

Cervical Cancer

Avastin in combination with paclitaxel and cisplatin or paclitaxel and topotecan is indicated for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix.

Avastin’s Mechanisms of Action

Angiogenesis is the process by which new blood vessels are created from pre-existing vessels.2 Angiogenesis plays a vital role in tumour formation and metastasis, first by providing tumours with nutrients and oxygen, and then by providing access to the systemic lymphatic and circulatory systems. The key mediator of angiogenesis, vascular endothelial growth factor (VEGF), is critical for the growth of tumours and their subsequent metastasis.3

Avastin is a recombinant, humanised monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human VEGF. Neutralising the biologic activity of VEGF reduces tumour angiogenesis, thereby inhibiting tumour growth.4

For a short video explaining Avastin’s mode of action click the image below.

Avastin’s Funding Status

Avastin is not funded by PHARMAC and patients need to pay for it.

We provide a Patient Cost Share Programme to assist with the cost of Avastin. Please refer to the Patient Cost Share Programme section below for details.

If your patient has private health insurance, it may be worthwhile they check their policy regarding cancer treatments like Avastin.

References

  1. Avastin® (bevacizumab) Data Sheet. Available here.
  2. Carmeliet P. Angiogenesis in health and disease. Nat Med 2003;9(6):653-60.
  3. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003;3(6):401-10.
  4. Presta LG, Chen H, O'Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57(20):4593-9.

The Avastin Cost Share Programme (ACSP) assists with the cost of Avastin for New Zealand patients with the following cancer types:

  • Metastatic colorectal cancer
  • Metastatic renal cell cancer
  • Advanced non-squamous non-small-cell lung cancer
  • Metastatic breast cancer
  • Advanced epithelial ovarian, fallopian tube or primary peritoneal cancer
  • Glioblastoma multiforme
  • Persistent, recurrent, or metastatic carcinoma of the cervix

The Avastin Cost Share Programme is available within the Medsafe-approved indications only. For further information on these indications, please refer to the 'About Avastin' section above.

If your patient has private health insurance, it may be worthwhile they check their policy regarding cancer treatments like Avastin.

Health Insurance Quick Guide

All the details of the Avastin Cost Share Programme are in the Prescriber Information brochure. Click on the image below to download a copy.

ACSP_PrescriberInformation

Click on the image below to download a copy of the Cost Share Programme Enrolment Form.

ACSP_EnrolmentForm

Click on the image below to download a copy of the Cost Share Programme Claim Form.

ACSP_ClaimForm

Key Efficacy and Safety Information

Avastin in combination with chemotherapy has been shown to improve survival in patients with a wide range of tumours (mCRC, mBC, mOC, cervical cancer, mRCC and mNSCLC) compared with chemotherapy alone. Avastin as a single agent improves survival in patients with GBM, compared with chemotherapy.1

Metastatic colorectal cancer (mCRC)

Avastin in combination with fluoropyrimidine-based chemotherapy has been shown to improve overall survival and progression free survival in first and second line mCRC, compared to chemotherapy alone.2-4 In the first-line mCRC setting, the improvement in survival is observed with both irinotecan-and oxaliplatin-based fluoropyrimidine chemotherapy regimens and is independent of KRAS mutation status.2,5

Metastatic renal cell carcinoma (mRCC)

A Phase III international, randomized, double-blind trial (AVOREN) was conducted in previously untreated mRCC patients (n=649) who received either Avastin or placebo in combination with interferon-alpha (IFN-α).6 Avastin plus IFN-α significantly improved PFS (10.2 vs. 5.4 months; Hazard Ratio [HR]=0.63; p=0.0001) and overall response rate (31% vs. 13%; p<0.0001) compared with placebo + IFN-α. The median overall survival was 23.3 months vs. 21.3 months in the Avastin + IFN-α and placebo + IFN-α groups, respectively (HR=0.86; p=0.1291).

Metastatic non-small cell lung cancer (mNSCLC)

Study E4599 was a Phase III trial that was designed to evaluate paclitaxel and carboplatin (PC) +/- Avastin in patients with locally advanced, metastatic, or recurrent NSCLC.7 The median overall survival was extended from 10.3 months in the PC alone arm to 12.3 months in the Avastin plus PC arm (HR =0.79, p=0.003). Median PFS improved from 4.5 months in the PC alone arm to 6.2 months in the Avastin plus PC arm (HR=0.66, p<0.001). Overall response rate increased in the Avastin plus PC arm to 35% compared to 15% in the PC alone arm (p<0.001).

Metastatic breast cancer (mBC)

Three large, randomized Phase III trials (E2100, AVADO and RIBBON-1) have demonstrated a significant improvement in PFS with the addition of Avastin to chemotherapy in previously untreated patients with human epidermal growth factor receptor 2 (HER2)-negative mBC.8-10 To date, none of the Phase III studies have demonstrated a significant overall survival benefit with Avastin-containing therapy in patients with previously untreated mBC.

Progressive gliobastoma multiforme (GBM)

A Phase II, open-label, multicentre, randomized, non-comparative study (AVF3708g, BRAIN Study) was conducted to evaluate the efficacy and safety of Avastin alone or in combination with irinotecan in 167 adult GBM patients with progressive disease following prior therapy.11 For single-agent Avastin, the objective response rate was 28.2%, and median duration of response was 5.6 months. Six-month PFS and median overall survival (OS) were 42.6% and 9.3 months, respectively. In the Avastin with irinotecan arm, ORR was 37.8% and median duration of response was 4.3 months. Six-month PFS and median OS were 50.3% and 8.9 months, respectively. Based on these data, Avastin is registered for use as a single agent.1

Advanced epithelial ovarian, fallopian tube and primary peritoneal cancer

GOG-0218 was a Phase III, international, multicentre, double-blind, placebo controlled trial in 1,873 women with previously untreated, advanced epithelial ovarian, primary peritoneal, or fallopian tube carcinoma.12 Following surgery, patients were randomized to 1 of 3 treatment arms: Arm I, carboplatin and paclitaxel (CP) followed by placebo; Arm II, CP+Avastin followed by placebo; Arm III, CP+Avastin followed by Avastin alone. Patients in Arm III demonstrated a significant improvement in progression-free survival (PFS) compared with patients who received CP alone (control arm [Arm I]) with a hazard ratio of 0.645 (p<0.0001); investigator assessed median PFS was 18.2 months vs 12 months, respectively.

The AURELIA study was a Phase III, international, open-label, randomised, two-arm trial in 361 women with platinum-resistant recurrent ovarian cancer.13 Investigators selected the single agent chemotherapy on an individual basis. Patients were then randomised to receive chemotherapy alone or with Avastin. The chemotherapy options included paclitaxel, pegylated liposomal doxorubicin or topotecan. Patients in the Avastin + chemotherapy arm demonstrated a significant improvement in progression-free survival (PFS) compared to patients who received chemotherapy alone with a hazard ratio of 0.48 (p<.001); median PFS was 6.7 months vs 3.4 months, respectively.

Metastatic cervical cancer

The Phase III GOG 240 trial was conducted to evaluate the addition of Avastin to chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) in patients with Stage IVB, recurrent, or persistent cervical cancer.14 The median overall survival was 17 months with the Avastin + chemotherapy arm and 13.3 months with the chemotherapy alone arm (hazard ratio=0.71; 98% CI, 0.54-0.95; p=0.004). Patients treated with Avastin + chemotherapy also demonstrated a significant improvement in progression-free survival compared with patients treated with chemotherapy alone (median progression free survival: 8.2 months vs 5.9 months; hazard ratio=0.67; 95% CI, 0.54-0.82; p=0.002).

Safety Information

For full safety information, please refer to the Avastin Data Sheet available here.1

Contraindications:

NSCLC patients with recent pulmonary haemoptysis.

Precautions:

Gastrointestinal perforation and fistulae

  • GI and gallbladder perforations, some serious and with a fatal outcome. Caution in patients with underlying intra-abdominal inflammation (e.g. GI disease, tumour necrosis, diverticulitis, and chemotherapy-associated colitits).
  • GI-vaginal fistulae in patients treated for cervical cancer. Caution in patients with a history of prior pelvic floor radiation.
  • Permanently discontinue Avastin in patients who develop perforation.

Non-GI fistulae

  • Increased risk of fistulae, some serious and with a fatal outcome.
  • Permanently discontinue in patients with trachea-oesophageal or any Grade 4 fistula.

Hypertension

  • Adequately control hypertension prior to treatment and monitor BP during therapy.
  • Permanently discontinue if medically significant hypertension can’t be controlled or hypertensive crisis/hypertensive encephalopathy develops.

Wound healing

  • Do not initiate for 28 days following major surgery or until wound fully healed.
  • Withhold Avastin for elective surgery and in patients who develop wound healing complications.
  • Serious wound healing complications with fatal outcome have been reported.
  • Rare cases of necrotising fasciitis, usually secondary to wound healing complications, GI perforation or GI fistula. Permanently discontinue in patients who develop necrotising fasciitis.

Thromboembolism - arterial

  • Arterial thromboembolic events (ATE) including CVAs, MI, TIAs and others have been reported, including some with fatal outcome.
  • Increased risk in patients ≥65 years, or with diabetes or a history of ATE.
  • Permanently discontinue in patients who develop ATE.

Thromboembolism - venous

  • Venous thromboembolic events including DVT and PE have been reported.
  • Closely monitor VTE Grade ≤ Grade 3.
  • Permanently discontinue in patients who develop life-threatening (Grade 4) VTE or PE.

Haemorrhage

  • Increased risk of tumour-associated haemorrhage and minor mucocutaneous haemorrhage such as epistaxis, gingival or vaginal bleeding.
  • CNS metastases and GBM-treated patients have been associated with intracranial bleeding. Monitor for signs and symptoms.
  • GI haemorrhage, including rectal bleeding and melaena reported in CRC patients.
  • Pulmonary haemorrhage/haemoptysis in NSCLC, including some with a fatal outcome.
  • Not recommended in patients with squamous cell histology or recent pulmonary haemorrhage/haemoptysis.
  • Caution starting treatment in patients on anti-coagulants, with acquired coagulopathy or congenital bleeding diathesis.
  • Permanently discontinue if Grade 3 or 4 bleeding.

Posterior Reversible Encephalopathy Syndrome (PRES)

  • Discontinue Avastin if patient experiencing signs and symptoms PRES.

Proteinuria

  • Patients with history of hypertension at risk of developing proteinuria.
  • Test for proteinuria prior to starting Avastin.
  • Permanently discontinue if nephrotic syndrome develops.

CHF

  • Caution in CV disease or CHF.
  • Increased risk with prior anthracycline exposure and radiation to chest wall

Neutropenia

  • Increased risk of severe neutropenia, febrile neutropenia ± infection, some with fatal outcome.

Hypersensitivity/infusion reactions

  • Anaphylactic/anaphylactoid reactions. Monitor patient closely during and following administration.
  • Permanently discontinue if reaction develops.

Other

  • Severe eye infections following compounding for unapproved intravitreal use
  • Ovarian failure and impairment of female fertility
  • Patients (>65 years): increased risk of ATE and higher frequency of leucopenia, thrombocytopenia, and all Grade neutropenia.

Pregnancy: Category D.

  • Use adequate contraception during, and for 6 months after therapy cessation
  • Discontinue breast-feeding during, and for 6 months following treatment cessation.

Adverse Effects: Most frequently reported in trials were hypertension, fatigue or asthenia, diarrhoea and abdominal pain. Very common and common AEs only listed below; see Data Sheet for full list. Some adverse reactions are reactions commonly seen with chemotherapy however Avastin may exacerbate some of these reactions when combined with chemotherapy.

  • Infections/infestations: sepsis, abscess, cellulitis.
  • Blood/lymph disorder: neutropenia (including febrile), leucopenia, thrombocytopenia, anaemia, lymphopenia.
  • Metabolism/nutrition disorder: dehydration, anorexia.
  • Nervous system disorder: peripheral sensory neuropathy, CVA, syncope, somnolence, headache, dysgeusia, dysarthria.
  • Eye disorder: lacrimation increased.
  • Cardiac disorder: cardiac failure congestive, supraventricular tachycardia.
  • Vascular disorder: hypertension, DVT, PE, haemorrhage.
  • Respiratory/thoracic disorder: PE, dyspnoea, hypoxia, epistaxis, rhinitis.
  • GI disorder: diarrhoea, nausea, vomiting, abdominal pain, GI perforation/fistulae, intestinal obstruction, ileus, stomatitis, proctalgia, constipation, rectal haemorrhage.
  • Endocrine: ovarian failure
  • Skin/SC disorder: palmar-plantar erythrodysaesthesia syndrome, exfoliative dermatitis, dry skin, discoloured skin.
  • Musculoskeletal disorder: muscular weakness, myalgia, arthralgia, back pain.
  • Renal/urinary disorder: UTI, proteinuria.
  • General disorders and administration site conditions: fatigue/asthenia, pain, lethargy, mucosal inflammation, pyrexia.
  • Reproductive: pelvic pain.

Please contact the Roche team for further information on the efficacy and/or safety of our products.

References

  1. Avastin® (bevacizumab) Data Sheet. Available here.
  2. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-2342.
  3. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group study E3200. J Clin Oncol 2007;25:1539-1544.
  4. Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised Phase 3 trial [supplementary appendix appears online]. Lancet Oncol 2013;14:29-37.
  5. Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized Phase III study [published corrections appear in J Clin Oncol 2009;27:653 and J Clin Oncol 2008;26:3110]. J Clin Oncol 2008;26(12):2013-9.
  6. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007;370:2103-2111.
  7. Sandler A, Gray R, Perry MC, et al. Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. N Engl J Med 2006;355:2542-2550.
  8. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666-2676.
  9. Miles DW, Chan A, Dirix LY, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 2010;28:3239-3247.
  10. Robert NJ, Diéras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, Phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 2011;29:1252-1260.
  11. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009;27:4733-4740.
  12. Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011;365(26):2473-83.
  13. Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol 2014;32(13):1302-8.
  14. Tewari S, Sill MW, Long HJ, et al. Improved Survival with Bevacizumab in Advanced Cervical Cancer. NEJM 2014;370:734-743.


The Avastin Consumer Medicine Information (CMI) leaflet is available here. For more patient information on Avastin please visit www.cancerinfo.co.nz.