Axumin (Blue Earth Diagnostics Ltd) is a molecular imaging agent. It is intended for use in positron emission tomography (PET) to detect whether prostate cancer has returned in people whose blood prostate-specific antigen (PSA) levels have risen after primary curative treatment. Axumin is given as an intravenous injection in the arm 3 to 5 minutes before a PET scan. A CT scan is used to provide information about the patient anatomy and the combined scan is termed PET/CT.
Axumin contains the active ingredient 18F‑fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid or FACBC). This is a radiolabelled synthetic amino acid that is taken up into cells by transporters (LAT‑1 and ASCT2) known to be present in high numbers on the surface of prostate cancer cells. Once inside the cancer cells, it emits radiation that is detected on the PET scan, with the aim of identifying local and distant areas of recurrence. The preferential uptake of the tracer into prostate cancer cells compared with the surrounding non-cancerous tissue enables cancerous areas to be reliably located.
Axumin is the only PET tracer currently licensed for clinical use in recurrent prostate cancer. Prostate-specific membrane antigen (68Ga‑PSMA) and choline-based (11C- and 18F‑labelled) PET tracers are available only on a special licence basis or for use in research. Expert advice indicates that these tracers are increasingly used in UK practice and that 18F‑choline PET/CT is currently the only scan commissioned by NHS England in the national PET/CT tender. Axumin is designed to more effectively identify recurrent disease across a wide range of PSA levels compared with standard-of-care imaging (pelvic CT or MRI and bone scans). These lack the sensitivity and specificity to detect prostate cancer when PSA levels are low (Mottet et al. 2017; Cornford et al. 2017). The short uptake period for Axumin allows scans to be done 3 to 5 minutes after administration, compared with alternative PET tracers, which may need about 1 hour for optimal tracer uptake. Also, the technology's shelf life of 7 to 10 hours may offer potential for wider use compared with 11C‑choline. This has a half-life of 20 minutes, meaning that it can only be done in PET centres with on-site cyclotron and radiopharmacy facilities.
NICE's guideline on prostate cancer: diagnosis and management recommends routine follow-up to identify recurrent disease in men who have had treatment for localised prostate cancer. According to the guideline, methods of monitoring disease control and detecting recurrence include physical examination, PSA blood tests and imaging investigations. It recommends that PSA levels are checked in everyone having curative-intent (or radical) treatment 6 weeks or more after treatment, at least every 6 months for the first 2 years and then at least once a year. To detect areas of local recurrence or metastatic lesions, it recommends imaging techniques such as MRI or bone scans in people with a rising PSA (biochemical relapse [BCR]) after curative-intent treatment, and who are considering second-line therapy. However, it recommends MRI only after salvage radiotherapy, and an isotope bone scan only if symptoms suggest metastasis. An update to this guideline is currently in process (expected publication date April 2019). In the draft of this update, several previous recommendations on imaging have been deleted, including the recommendation against using PET scans for prostate cancer in routine clinical practice (1.2.15). No new recommendations for managing relapse after radical treatment have been added.
The 2017 European guidelines on prostate cancer recommend routine follow-up of people who are asymptomatic at 3, 6 and 12 months after treatment, then every 6 months until 3 years, and then annually. Imaging to detect local recurrence is only recommended if it affects treatment planning. It also recommends that other imaging modalities should not be routinely offered to people who are asymptomatic if there are no signs of BCR. It states that re-staging should be considered irrespective of PSA levels if there is bone pain or other symptoms of progression. It also recommends the use of choline or PSMA PET/CT imaging in people with BCR after radical prostatectomy with PSA levels of 1 ng/ml or more. In people with low baseline PSA levels (that is, less than 1 ng/ml), no imaging is recommended. In people with BCR after radiotherapy, choline PET/CT imaging is recommended to rule out lymph nodes or distant metastases in patients fit enough for curative salvage treatment. It also states that bone scans and abdominopelvic CT should only be considered in patients with BCR after radical prostectomy or radiotherapy who have a high baseline PSA (greater than 10 ng/ml) or adverse PSA kinetics (PSA doubling time less than 6 months or PSA velocity greater than 0.5 ng/ml/month).
Axumin is indicated for PET imaging to detect suspected prostate cancer recurrence in adults with elevated blood PSA levels after primary curative treatment. Axumin will be used in nuclear medicine or radiology centres of tertiary centres. It will be administered by radiographers and the resultant PET/CT images will be read by nuclear medicine physicians.
According to the company, the per-patient cost for a single dose of Axumin tracer is £950 (excluding VAT), plus transport costs estimated at £50 to £250 per shipment (a shipment may include more than 1 dose). This does not include the cost of the scan and other consumables.
The cost of an MRI is £114 to £163, a CT is £71 to £85 and a bone scan is £181 (based on National Tariff 2018/19 and include the cost of reporting). According to the national schedule of reference costs 2017/18, the average cost of a PET/CT scan is £586 (HRG code RN01A). This includes the cost of the tracer, shipment and scan, but the tracer it includes is not used for prostate cancer.
If adopted, the technology would be used in addition to MRI and CT, but has the potential to replace bone scans and PET scans with specialised PSMA and choline-based tracers. Since equipment and staff needs would be comparable to those for PET scans used in other indications, there would only need to be minimal change to adopt the technology, and no facility or infrastructure modifications would be needed. Axumin, however, may potentially lead to an increase in the number of PET scans done, so may increase resource needs. Radiologists will need product-specific training on interpreting Axumin scans, and the company states that approved training programmes are available from the Medicines and Healthcare products Regulatory Agency and the Administration of Radioactive Substances Advisory Committee.
The use of Axumin PET is likely to be cost incurring compared with current standard care. However, because of increased detection compared with standard imaging, Axumin has the potential to be resource releasing by reducing the number of repeat scans done, and enabling earlier detection and subsequent treatment. In addition, Axumin may have the potential to influence subsequent treatment decisions, reducing the number of patients being under- or over-treated with salvage radiotherapy. The company also claims that Axumin use has the potential to reduce the pre-patient scan time compared to alternative PET tracers.
The results of a US cost-consequence study (Jensen et al. 2017, published as an abstract only) suggests that increased use of the technology for suspected prostate cancer recurrence may lead to better clinical outcomes while being cost neutral. Results from this study found that Axumin use reduced the number of imaging procedures by 27% and led to a 13% increase in correct diagnoses. There was a small cost increase of 3% per correct diagnosis from $24,870 to $25,589.