Vascular endothelial growth factor (VEGF) / vascular endothelial growth factor receptor (VEGFR) inhibitors

MHRA Drug Safety Update (July 2020): Systemically administered VEGF pathway inhibitors: risk of aneurysm and artery dissection

1. Before initiating a systemic VEGF pathway inhibitor, carefully consider the risk of aneurysm and artery dissection in patients with risk factors (see Drug Safety Update for a list of risk factors)
2. In patients who receive a systemic VEGF pathway inhibitor, reduce as far as possible any modifiable risk factors such as smoking and hypertension
3. Monitor patients for and treat hypertension in accordance with recommendations in the SPC (click here)

Bevacizumab

• Solution for infusion vials 100mg/4ml, 400mg/16ml
• Intravitreal injection 5mg/0.2ml (unlicensed preparation)

Indications

• Neovascular (wet) age related macular degeneration
• Prior to vitrectomy in patients with proliferative diabetic retinopathy
• Radiation maculopathy
• Rubeosis iridis and neovascular glaucoma (see notes below)
• For use in line with NICE TAs listed below

Notes

1. The decision to offer bevacizumab intravitreal injection is at the discretion of the treating clinician. The patient must be made fully aware that bevacizumab intravitreal injection is an unlicensed preparation and give informed consent to its use.
2. The routine commissioning of bevacizumab is accepted in Devon for the first line treatment of neovascular (wet) age related macular degeneration (see Commissioning Policy for more details).
3. The routine commissioning of bevacizumab is accepted in Devon for use prior to vitrectomy in patients with proliferative diabetic retinopathy (see Commissioning Policy for more details).
4. The routine commissioning of bevacizumab intravitreal injection is accepted in Devon for the management of radiation maculopathy (see Commissioning Policy for more details).
5. The routine commissioning of bevacizumab intravitreal injection is accepted in Devon for the management of rubeosis iridis and neovascular glaucoma only in the following circumstances (see Commissioning Policy for more details):
   1. As an adjunct to pan-retinal laser photocoagulation where laser alone has not been effective, or
   2. As an adjunct to pan-retinal laser photocoagulation if significant neovascularisation of the iridocorneal angle is already present, or
   3. In the presence of media opacities which prevent the use of pan-retinal laser photocoagulation.
6. NICE TA118: Bevacizumab (Avastin) in combination with 5-fluorouracil plus folinic acid, with or without irinotecan, is not recommended for the first-line treatment of metastatic colorectal cancer (January 2007).
7. NICE TA212: Bevacizumab (Avastin) in combination with oxaliplatin and either fluorouracil plus folinic acid or capecitabine is not recommended for the treatment of metastatic colorectal cancer (December 2010).
8. NICE TA242: Bevacizumab (Avastin) in combination with non-oxaliplatin (fluoropyrimidine-based) chemotherapy is not recommended for the treatment of people with metastatic colorectal cancer that has progressed after first-line chemotherapy (January 2012).
9. NICE TA178: Bevacizumab (Avastin), sorafenib (Nexavar), and temsirolimus (Torisel) are not recommended as first-line treatment options for people with advanced and/or metastatic renal cell carcinoma (August 2009).
10. NICE TA214: Bevacizumab (Avastin) in combination with a taxane is not recommended for the first-line treatment of metastatic breast cancer (February 2011).
11. NICE TA263: Bevacizumab (Avastin) in combination with capecitabine is not recommended within its marketing authorisation, for the first-line treatment of metastatic breast cancer, that is, when treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate, or when taxanes or anthracyclines have been used as part of adjuvant treatment within the past 12 months (August 2012).
12. NICE TA284: Bevacizumab (Avastin) in combination with paclitaxel and carboplatin is not recommended for first-line treatment of advanced ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] stages IIIB, IIIC and IV epithelial ovarian, fallopian tube or primary peritoneal cancer) (May 2013).
13. NICE TA285: Bevacizumab (Avastin) in combination with gemcitabine and carboplatin is not recommended within its marketing authorisation, that is, for treating people with the first recurrence of platinum-sensitive advanced ovarian cancer (including fallopian tube and primary peritoneal cancer) who have not received prior therapy with bevacizumab or other vascular endothelial growth factor (VEGF) inhibitors or VEGF receptor-targeted agents (May 2013).
14. NICE TA666: Atezolizumab (Tecentriq) plus bevacizumab (Avastin) is recommended as an option for treating advanced or unresectable hepatocellular carcinoma (HCC) in adults who have not had previous systemic treatment (December 2020), only if:
    1. they have Child‑Pugh grade A liver impairment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and
    2. the company provides it according to the commercial arrangement.
15. NICE TA946: Olaparib (Lynparza) with bevacizumab (Avastin) is recommended, within its marketing authorisation, for maintenance treatment of high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer in adults (January 2024) whose cancer:
    1. has completely or partially responded after first-line platinum-based chemotherapy with bevacizumab,
    2. is advanced (International Federation of Gynaecology and Obstetrics [FIGO] stages 3 and 4) and
    3. is homologous recombination deficiency (HRD) positive (defined as having either a BRCA1 or BRCA2 mutation, or genomic instability).
16. MHRA Drug Safety Update (June 2010) Bevacizumab (Avastin): hypersensitivity and infusion reactions. Infusion reactions and hypersensitivity reactions have been reported commonly during treatment with Avastin.
17. MHRA Drug Safety Update (January 2011) Bevacizumab and sunitinib: risk of osteonecrosis of the jaw (ONJ)
    1. Treatment with bevacizumab or sunitinib may be a risk factor for the development of ONJ.
    2. Patients treated who have previously received, or are treated concurrently with, bisphosphonates may be particularly at risk.
    3. Dental examination and appropriate preventive dentistry should be considered before treatment with bevacizumab or sunitinib; invasive dental procedures should be avoided, if possible, in patients treated with bevacizumab or sunitinib who have previously received, or who are receiving, intravenous bisphosphonates.

Tivozanib

• Capsules 890micrograms, 1.34mg

Notes

1. NICE TA512: Tivozanib (Fotivda) is recommended as an option for treating advanced renal cell carcinoma in adults (March 2018), only if:
   1. they have had no previous treatment and
   2. the company provides tivozanib with the discount agreed in the patient access scheme.

Ramucirumab

• NICE TA378: Ramucirumab (Cyramza) alone or with paclitaxel is not recommended within its marketing authorisation for advanced gastric cancer or gastro–oesophageal junction adenocarcinoma previously treated with chemotherapy (January 2016).
• NICE TA403: Ramucirumab (Cyramza), in combination with docetaxel, is not recommended within its marketing authorisation for treating locally advanced or metastatic non-small-cell lung cancer in adults whose disease has progressed after platinum-based chemotherapy (August 2016).

Vandetanib

• NICE TA550: Vandetanib (Caprelsa) is not recommended within its marketing authorisation for treating aggressive and symptomatic medullary thyroid cancer in adults with unresectable, locally advanced or metastatic disease (December 2018).