England’s clinical and cost-effectiveness agency has said that it would not recommend lapatinib or trastuzumab with aromatase inhibitors as first-line treatments for postmenopausal women with HER2 positive metastatic breast cancer.
The new negative draft guidance follows previous negative guidance, issued in July 2011, and a subsequent appeal by Roche, the manufacturer of trastuzumab (Herceptin). While an independent panel upheld parts of Roche’s appeal in November, the National Institute for Health and Clinical Excellence nonetheless rejected both treatments once more, citing cost concerns and unclear overall survival evidence for this patient group.
In clinical trial results evaluated by NICE, lapatinib plus an aromatase inhibitor was associated with progression-free survival of 5.2 months, and trastuzumab plus an aromatase inhibitor with 2.4 months; however, NICE said that there was insufficient evidence of an overall survival gain with either treatment.
While NICE has never before issued guidance on lapatinib (Tyverb and Tykerb, GlaxoSmithKline) for any indication, trastuzumab is currently recommended by NICE for the treatment of HER2 positive gastric cancer and for two groups of women with breast cancer: those whose tumors overexpress HER2 at levels of 3+ who have not had chemotherapy for metastatic breast cancer and for whom anthracycline is inappropriate (for this group, trastuzumab is recommended in combination with paclitaxel); and those who have early-stage HER2 positive breast cancer following surgery and chemotherapy.
Lapatinib and trastuzumab combined with aromatase inhibitors are being assessed as treatments for women only when chemotherapy is deemed unsuitable.
Trastuzumab, a humanized monoclonal antibody directed against HER2, is administered as an intravenous infusion of 4 mg/kg, followed by a weekly maintenance dose of 2 mg/kg until disease progression (or an alternative schedule of 8 mg/kg followed by 3-weekly doses of 6 mg/kg). NICE estimates the cost of treatment with trastuzumab plus the aromatase inhibitor anastrozole to be between £26,000 and £27,000, depending on the dosing schedule.
Lapatinib, an oral medication, is administered in six tablets totaling 1,500 mg/day. Treatment with lapatinib plus the aromatase inhibitor letrozole is estimated at about £28,000.
NICE said that the estimated incremental cost effectiveness ratio for lapatinib plus letrozole, compared with letrozole alone, is about £74,400 per quality-adjusted life year gained. Trastuzumab plus anastrozole, compared with anastrozole alone, is estimated at £51,000 per QALY gained. Both estimates surpass NICE’s cost-effectiveness caps.