Erlotinib Monotherapy for the Maintenance Treatment of Non-Small Cell Lung Cancer after Previous Platinum-Containing Chemotherapy

Abstract

The UK National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of erlotinib (Roche) to submit evidence for the clinical and cost effectiveness of erlotinib as monotherapy for the maintenance treatment of patients with non-small cell lung cancer (NSCLC) and stable disease following previous treatment with four cycles of platinum-containing therapy. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. The ERG reviewed the clinical- and cost-effectiveness evidence in two stages and in accordance with the decision problem defined by NICE. The analysis of the submitted models assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. Analysis also included reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to have substantial impact on the base-case cost-effectiveness results. Clinical evidence was derived from a multi-centre, double-blind, randomized, phase III study designed to address the overall population of NSCLC patients. Outcomes included progression-free survival (PFS) and overall survival (OS). The recruited population was mainly from outside of Western Europe and no patients in the pivotal trial had received pemetrexed as a first-line therapy, which is now accepted clinical practice in the UK. The evidence considered in this article includes only the population for whom marketing authorizations has been received--that is, patients with stable disease following first-line therapy. The trial reported a small but statistically significant increase in both PFS and OS in patients with stable disease receiving erlotinib compared with placebo. However, no significant difference was identified in OS when patients with non-squamous disease and stable disease were considered as a subgroup. The economic evidence was focussed on the ERG's assessment of three economic models that related to patients with stable disease and compared erlotinib with placebo in the squamous and non-squamous populations and erlotinib with pemetrexed in the non-squamous population. The incremental cost-effectiveness ratios (ICERs) reported by the manufacturer were £39,936 per QALY gained (stable disease, all); £35,491 per QALY gained (stable disease, squamous); and £40,020 per QALY gained (stable disease, non-squamous). In comparison with pemetrexed, in the cases where erlotinib was considered to be superior or equivalent, erlotinib dominated. In the cases where erlotinib was considered to be slightly inferior, then the ICERs ranged between £91,789 and £511,351 per QALY gained; these ICERs appear in the south-west corner of a cost-effectiveness plane, i.e. erlotinib is cheaper but less effective than pemetrexed. The ERG recalculated the base-case cost-effectiveness results in the manufacturer's ...

Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer

“…Three studies have indirectly compared direct medical costs between maintenance with pemetrexed and maintenance with another drug (Table 8). 20,27,28 A US study showed that pemetrexed maintenance is more cost-effective for patients with non-squamous NSCLC than erlotinib, because the ICER for pemetrexed versus erlotinib (US $150,260/LYG) is within the acceptable range of willingness to pay 20. Another UK study also showed a clear advantage in favor of pemetrexed, ICER for erlotinib versus pemetrexed, £84,029/QALY gained 27.…”

“…20,27,28 A US study showed that pemetrexed maintenance is more cost-effective for patients with non-squamous NSCLC than erlotinib, because the ICER for pemetrexed versus erlotinib (US $150,260/LYG) is within the acceptable range of willingness to pay 20. Another UK study also showed a clear advantage in favor of pemetrexed, ICER for erlotinib versus pemetrexed, £84,029/QALY gained 27. In contrast, a European cross-market cost comparison showed that total monthly treatment costs per patient, including acquisition costs, administration costs, and costs of treating adverse events, were more reasonable for erlotinib than for pemetrexed, ie, €2,140 for erlotinib versus €3,453 for pemetrexed in France, €2,732 versus €5,534 in Germany, €1,518 versus €2,921 in Italy, and €2,048 versus €3,164 in Spain 28.…”

Clinicopathologic features of non-small cell lung cancer in India and correlation with epidermal growth factor receptor mutational status

“…[34] Dickson et al, reported a statistically significant increase in both PFS and OS in patients with stable disease receiving switch maintenance with erlotinib compared with placebo for the maintenance treatment of NSCLC after previous platinum-containing chemotherapy. [35] A Phase II study of sequential erlotinib and chemotherapy as firstline treatment for advanced NSCLC by Mok et al, also showed sequential administration of erlotinib following gemcitabine/platinum chemotherapy led to a significant improvement in PFS. [36] Similarly, Coudert et al, showed that patients with advanced NSCLC following firstline platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy.…”

Update on the treatment of non-small-cell lung cancer: focus on the cost-effectiveness of new agents

“…When the manufacturer submitted the dossier to NICE, the UK agency redid the calculations and found that erlotinib was not cost-effective for the British health care system 28. The NICE values were approximately £ 50,000 per QALY.…”