Evidence

STELFONTA^® is not a conventional chemotherapy cytotoxic agent that inhibits cell division or protein synthesis. In contrast to conventional cytotoxic chemotherapies used in cancer treatment, STELFONTA^® functions by stimulating cell signals which generate host responses against the tumour, as well as directly compromising the viability of the tumours cells themselves and tumour vasculature. These effects lead to tumour destruction without causing genotoxicity and the associated, and often severe, side effects that can occur with cytotoxic anticancer therapies. STELFONTA^® is not a biologic as it is not derived from human, animal or microorganisms.

A surgical biopsy is necessary for definitive differentiation between a cutaneous and subcutaneous MCT. However, characteristics on physical examination may help determine if they are cutaneous or subcutaneous MCTs. If any part of the MCT feels like it is attached to the overlying skin, it is likely cutaneous in origin. Cutaneous MCTs are located in the dermis and commonly extend into the epidermis and subcutaneous tissues. Only those MCT that are located entirely in the subcutis surrounded by adipose tissue are considered subcutaneous.

MCTs preferentially metastasise to lymph nodes, liver and spleen. Other sites of metastasis are uncommon. A thorough physical examination should include palpation of all lymph nodes for enlargement as well as abdominal palpation to evaluate for hepatomegaly and/or splenomegaly. Regional draining lymph node assessment via fine needle aspirate cytology or biopsy is recommended on all patients to rule out regional metastasis regardless of the size of the lymph node on palpation.

High grade tumours can be treated with STELFONTA^®. All grades of non-resectable non-metastatic, MCTs are indicated for treatment by STELFONTA^®.

Efficacy of the product in high grade tumours (as determined by cytological grading) was only evaluated in a limited number of cases. 10 out of 13 tumours in the study that were categorised as either "high grade" or "suspected high grade" received STELFONTA^®. Of these, 5 achieved a complete response after 1 or 2 treatments, 4 of which were still tumour free after 84 days after their final treatment. From the 5 complete response cases, 3 were confirmed being "high grade", and 2 were of "suspected high grade".

The small number of cases of high-grade tumours in the clinical study is based on the prevalence of high-grade tumours compared to other grades of non-metastatic MCTs.

STELFONTA^® treatment causes a change in the tissue architecture. It is therefore unlikely that an accurate histological tumour grading can be obtained after treatment.

Cytological grading can be used prior to treatment with STELFONTA^®.

Minimal staging should include evaluation of the sentinel lymph node with palpation and cytology with further diagnostic testing if indicated.^{Warland J1, Amores-Fuster I, Newbury W, Brearley M, Dobson J. The utility of staging in canine mast cell tumours. Vet Comp Oncol. 2014 Dec;12(4):287-98.}

The mode of action of STELFONTA^® is unrelated to the c-kit mutation. The efficacy following STELFONTA^® intratumoural injection would be unlikely to be affected by c-kit status of the treated MCT.

In cases where an MCT has been biopsied, it is important to allow for the biopsy site to fully heal. This can take 14-28 days depending on the size of biopsy punch used and an individual’s wound healing ability. Treating a tumour prior to healing of the biopsy site may lead to leakage of drug from the biopsy site, leading to inaccurate dosing and increased risk of a reduced response. We recommend MCT grading using cytology to reduce problems with adequate site healing following biopsy.

It is recommended to use a Luer Lock syringe when using STELFONTA^®. Increased intratumoural pressure during injection can lead to separation between the needle and syringe when a Luer Lock syringe is not used.

This can result in loss of STELFONTA^® leading to insufficient dosing and increased risk of accidental exposure to STELFONTA^® to attending staff.

Injection into non-neoplastic tissues can cause a transient, local response resulting in localised inflammation, oedema, redness and pain. Cases of wound formation have been observed following subcutaneous injection of STELFONTA^®.

It is recommended to NOT recap the needle following injection, to minimise the risk of accidental self-injection. The needle and syringe should be disposed of in accordance with local medical waste requirements.

The concomitant medications are mandatory prior to STELFONTA^® treatment of MCT. Failure to give these medications can lead to an increased risk of degranulation. Treatment should be delayed to allow these medications to be given as directed on the label.

Any manipulation of an MCT can lead to a mast cell degranulation reaction. This risk can be minimised by ensuring that concomitant medications of corticosteroids, H1 and H2 antagonists are received as directed on label.

Hospitalisation is not normally required following STELFONTA^® treatment but is at the discretion of the attending veterinarian.

There are no mandatory rechecks following STELFONTA^® treatment. Possible rechecks may include:

• Within the first 48 hours to assess compliance with taking concomitant medication and assessment of pain management.
• At week one, for size of wound and addressing any owner concerns.
• At week four, assessment for tumour response and determination if further treatments are necessary.

Further assessments for wound healing and/or recurrence should be at the discretion of the attending veterinarian.

The wounds typically resolve by second intention healing with minimal or no intervention required. In a small number of cases, additional care of the treated site may be needed to aid in the healing process. Potential wound management measures required are at the discretion of the attending veterinarian.

The treatment site should be covered for the first day after treatment in order to prevent direct contact with residual or leaking product. Handle the cover with gloves to avoid contact with the product. In case of severe leakage of wound debris, which may occur in the first weeks following administration of the product, the wound should be covered.

Where possible, bandaging should be avoided after the initial wound cover is removed. If bandaging is deemed necessary beyond the first day, it must be loose to allow for anticipated local oedema following STELFONTA^® treatment.

Patients that have restricted access to the site (to lick the site) may have a delay in the removal of the necrotic tissue which may slow healing. Removal of this tissue may be necessary in these cases. Avoid removing/ debriding tissue that is still well attached.

If there is concern of excessive licking or trauma to the site, an Elizabethan collar or loose dry gauze bandage can be used to prevent self-trauma by the dog.

The site can be cleaned/ flushed with water in cases of excessive discharge or smell. In case of severe leakage of wound debris, which may occur in the first weeks following administration of the product, the wound should be covered.

The use of antibiotics to treat wounds is at the discretion of the treating veterinarian.

In clinical trials, antibiotics were given in 47/123 patients with 14 of these cases to treat wounds. Only one case in the pivotal trial had a culture and sensitivity analysed. This patient had a mixed bacterial culture which was sensitive to the majority of antibiotics.

Removal of the necrotic tissue is not normally required when the patient is allowed access to the site. In cases where patients can’t access the site, the removal of necrotic tissue can be delayed which may slow the healing stage.

Avoid removing/ debriding necrotic tissue that is still well attached.

Bandaging of the wound is at the discretion of the attending veterinary surgeon. It is important to discuss the expected wound healing process following STELFONTA^® treatment prior to treatment so that owners are fully aware of what to expect.

Adequate information for the client helps to manage owner expectations and often alleviates their concerns.

If there are concerns about the appearance of a wound, it is recommended to discuss the benefits of leaving the wound uncovered. Bandaging of the wound may delay wound healing.

If the owner is still concerned, bandaging can be used until the owner is happy to leave the wound uncovered. It is recommended to discuss leaving the wound uncovered at each bandage change.

Any manipulation of an MCT can lead to a mast cell degranulation reaction. This risk can be minimised by ensuring that concomitant medications of corticosteroids, H1 and H2 antagonists are received as directed on label. The patient should be monitored for signs of degranulation for the first week following STELFONTA^® treatment. These signs include vomiting, diarrhoea, lethargy, anorexia/hyporexia, altered breathing, urticaria, oedema at or away from the treated site, bruising at or away from the treated site, and hypotension. Management of any adverse events should be left to the discretion of the attending veterinarian on an individual case basis.

Any manipulation of a MCT can lead to a mast cell degranulation reaction. This risk can be minimised by ensuring that concomitant medications of corticosteroids, H1 and H2 antagonists are received as directed on label.

• Corticosteroid: Start medication 2 days prior to STELFONTA^® treatment and continue for 8 days post-treatment (10 days total).
• H1 receptor blocking agent: Start medication on the day of STELFONTA^® treatment and continue until 8 days post treatment or until the mass has sloughed.
• H2 receptor blocking agent: Start medication on the day of STELFONTA^® treatment and continue until 8 days post treatment or until the mass has sloughed

Any manipulation of a MCT can lead to a mast cell degranulation reaction. This risk can be minimised by ensuring that concomitant medications of corticosteroids, H1 and H2 antagonists are received as directed on label. Degranulation reactions can be:

• localised: swelling, redness, bruising and haemorrhage at the tumour site.
• systemic: vomiting, hematemesis, diarrhoea, melena, lethargy, anorexia/hyporexia, altered breathing, urticaria, oedema at or away from the treated site, bruising at or away from the treated site, coagulopathies, generalised pruritis, hypotension, anaphylaxis and death.