Advice

Evidence review: safety

Evidence review: safety

Precautions for use

The manufacturer of bevacizumab (Avastin, Roche) warned about the risk of necrotising fasciitis associated with bevacizumab in May 2013 in information sent to healthcare professionals about the safety of medicines. The summary of product characteristics (SPC) lists adverse reactions that may be associated with bevacizumab treatment. These include gastrointestinal perforations, fistulae, wound healing complications, hypertension, posterior reversible encephalopathy syndrome, proteinuria, arterial and venous thromboembolism, haemorrhage, pulmonary haemorrhage or haemoptysis, congestive heart failure, neutropenia and infections, hypersensitivity or infusion reactions, osteonecrosis of the jaw, eye disorders, and ovarian failure.

The safety and efficacy of bevacizumab has not been studied in children, or in people with renal or hepatic impairment. It is contraindicated in people with hypersensitivity to the active substance, Chinese hamster ovary (CHO) cell products, or other recombinant human or humanised antibodies. Bevacizumab is also contraindicated in pregnancy. The SPC advises that women of childbearing potential should use effective contraception during and up to 6 months after treatment and breastfeeding should be avoided during and for at least 6 months after treatment.

Adverse drug reactions have been reported with sunitinib, platinum- or taxane-based therapies and epithelial growth factor receptor (EGFR) monoclonal antibodies when used in combination with bevacizumab.

For full details of adverse reactions and contraindications, see the summary of product characteristics.

Adverse events reported in the randomised controlled trial

The ICON7 trial reported 5 deaths that were related to treatment or to treatment and disease. One occurred in the standard chemotherapy group due to central nervous system (CNS) ischaemia. Four occurred in the standard chemotherapy plus bevacizumab group. These were due to gastrointestinal perforation, intracerebral haemorrhage, recurrent bowel perforation and ovarian cancer, and neutropenic sepsis and ovarian cancer.

Adverse events were common in both groups. Any adverse events of grade 1 or 2 were reported in 44% of women in the standard chemotherapy group and 34% of those in the bevacizumab group. Grade 3 or higher adverse events were reported in 56% of women in the standard chemotherapy group and 66% of those in the bevacizumab group.

Adverse events occurred more frequently in women receiving bevacizumab including:-

  • bleeding other than mucocutaneous tumour-associated, or within the CNS, grade 1 or 2 (standard chemotherapy n=39 [5%] compared with bevacizumab n=55 [7%])

  • mucocutaneous bleeding grade 1 or 2 (standard chemotherapy n=55 [7%] compared with bevacizumab n=271 [36%]) and grade 3 or higher (standard chemotherapy n=0 compared with bevacizumab n=5 [1%])

  • bleeding within the CNS grade 3 or higher (standard chemotherapy n=0 compared with bevacizumab n=2 [<1%])

  • abscess and fistula grade 1 or 2 (standard chemotherapy n=3 [<1%] compared with bevacizumab n=7 [1%])

  • gastrointestinal perforation grade 3 or higher (standard chemotherapy n=3 [<1%] compared with bevacizumab n=10 [1%])

  • any thromboembolic event grade 1 or 2 (standard chemotherapy n=22 [3%] compared with bevacizumab n=29 [4%]) and grade 3 or higher (standard chemotherapy n=23 [3%] compared with bevacizumab n=51 [7%])

  • complications of wound healing grade 1 or 2 (standard chemotherapy n=13 [2%] compared with bevacizumab n=27 [4%]) and grade 3 or higher (standard chemotherapy n=3 [<1%] compared with bevacizumab n=10 [1%])

  • hypertension grade 1 (standard chemotherapy n=31 [4%] compared with bevacizumab n=57 [8%]), grade 2 (standard chemotherapy n=14 [2%] compared with bevacizumab n=90 [12%]) and grade 3 or higher (standard chemotherapy n=2 [<1%] compared with bevacizumab n=46 [6%]).