On 20 March 2019, NICE issued Technology appraisal guidance [TA569] with evidence-based recommendations on pertuzumab (Perjeta, Roche) for adjuvant treatment of human epidermal growth factor receptor 2 (HER2)-positive early stage breast cancer in adults at high risk of recurrence.
Pertuzumab, with intravenous trastuzumab and chemotherapy, is recommended for the adjuvant treatment of HER2-positive early stage breast cancer in adults, only if:
- they have lymph node-positive disease
- the company provides it according to the commercial arrangement.
Dosage in the marketing authorisation is intravenous 840 mg loading dose, then 420 mg every 3 weeks. Pertuzumab should be given with trastuzumab and chemotherapy for 1 year (maximum 18 cycles) for patients with high-risk disease, regardless of the timing of surgery.
Pertuzumab costs 2,395 GBP per 420‑mg vial; trastuzumab costs 407.40 GBP per 150‑mg vial (excluding VAT; British national formulary online, accessed May 2018).
The company has a commercial arrangement. This makes pertuzumab available to the NHS with a discount. The size of the discount is commercial in confidence. It is the company's responsibility to let relevant NHS organisations know details of the discount.
This guidance is not intended to affect adjuvant treatment with pertuzumab that was started in the NHS before this guidance was published. Patients having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.
Why the appraisal committee made these recommendations?
There is uncertainty about the size of the clinical benefit for pertuzumab in the adjuvant treatment of HER2‑positive early stage breast cancer at high risk of recurrence. Clinical trial evidence measuring invasive disease-free survival suggests that 1.7% fewer patients with this type of cancer have invasive disease at 4 years with adjuvant pertuzumab. Evidence from patients with lymph node-positive disease suggests more benefit in this population, with 3.2% fewer patients having invasive disease at 4 years. However, it is not known whether this means that adjuvant pertuzumab increases the overall survival.
Because of the uncertainty in the clinical-effectiveness evidence, the cost-effectiveness estimates are very uncertain. Given this uncertainty, an estimate above 20,000 GBP per quality-adjusted life year (QALY) gained is not considered a cost-effective use of NHS resources. The company's final model includes only patients with lymph node-positive disease, and incorporates the committee's preferred conservative estimates of how long treatment benefit with pertuzumab lasts after treatment is stopped. If the commercial discount to the price of pertuzumab, together with a weighted discount for biosimilar intravenous trastuzumab are taken into consideration, the cost-effectiveness estimate is comfortably below 20,000 GBP per QALY gained. Therefore, adjuvant pertuzumab is recommended for HER2-positive early stage breast cancer in patients with lymph node-positive disease.
Next review is foreseen inMarch 2022.