Lapatinib is licensed for the treatment of patients with breast cancer, whose tumours overexpress HER2 in combination with capecitabine for patients with advanced or metastatic disease with progression following prior therapy, which must have included anthracyclines and taxanes and therapy with trastuzumab in the metastatic setting. In May 2010, NICE issued a FAD which did not support this use of lapatinib in combination with capecitabine, except in the context of clinical trials, as it was not a cost-effective use of NHS resources, even taking into account the proposed patient access scheme. This FAD has now been withdrawn following an appeal from the manufacturers and because of the extension of the review of technology appraisal guidance. The SMC did not support this use of lapatinib in NHS Scotland as the manufacturer was not considered to have presented a sufficiently robust economic analysis to gain acceptance by the SMC and the justification of the treatment’s cost in relation to its health benefits was also not considered sufficient.

The data in support of this use of lapatinib in this patient group come from one RCT, which closed early following an interim analysis showing improvement in time to progression in the lapatinib plus capecitabine group compared with the capecitabine monotherapy group. All women in the control arm were subsequently offered lapatinib in combination with capecitabine (36 crossed over at the time of unblinding). Data from the April 2006 cut-off date evaluated by NICE, for 198 patients in the combination group and 201 patients in the monotherapy group, showed median time to progression of 27.1 weeks for combination therapy and 18.6 weeks for monotherapy (p<0.001),with a tolerable toxicity profile. However, there was no statistically significant difference in median overall survival: (67.7 weeks for combination and 66.6 weeks for monotherapy). Subsequent annual analysis of survival data over 2 years failed to detect a statistically significant survival benefit for the combination arm, which may possibly be confounded by crossover of some patients to combination therapy. It has been postulated that lapatinib may reduce the risk of developing CNS metastases but further studies are required to confirm this.