ABSTRACT
As a novel third-generation ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown excellent systemic and intracranial activity in non-small cell lung cancer (NSCLC) patients who carry sensitizing ALK-activating mutations and progress on first- and second-generation TKIs. In comparison with other ALK-TKIs, lorlatinib has a unique safety profile for hyperlipidemia and central nervous system adverse events. Lorlatinib-induced adverse events are well tolerated, permanent discontinuations are rarely reported, and dose modifications and/or standard medical therapy are useful for the management of adverse events. Our present study reviews the safety profile of lorlatinib as well as the relevant management strategies. Our present study aims to provide a practical guide for the scientific management and application of lorlatinib.
ABSTRACT
INTRODUCTION: The JAVELIN Bladder 100 trial showed that maintenance avelumab therapy after chemotherapy improved the survival of patients with advanced or metastatic urothelial carcinoma. We analyzed the cost-effectiveness of maintenance therapy with avelumab plus best supportive care (BSC) in patients with advanced or metastatic urothelial carcinoma after receiving first-line platinum-based chemotherapy from the US payer perspective. METHODS: A Markov model was used to analyze the economic outcomes of maintenance avelumab plus BSC (avelumab strategy) in the treatment of urothelial carcinoma. The clinical data were derived from the JAVELIN Bladder 100 trial. All cost information was obtained from Medicare and published literature. The total cost, total life years (LYs), total quality-adjusted LYs (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net health benefit (INHB) were calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed. RESULTS: Our results showed that avelumab strategy versus BSC strategy cost US $176,352 and $238,661 and yielded an additional 0.465 and 1.007 QALY in all patients with unknown programmed-death ligand 1 (PD-L1) status and the PD-L1-positive subpopulation, respectively, which led to an ICER of $102,365/QALY and $106,253/QALY gained. In all patients with unknown PD-L1 status, maintenance avelumab plus BSC therapy guiding by PD-L1 expression testing (PD-L1-guided strategy) compared with the avelumab strategy and BSC strategy resulted in ICER of $105,360/QALY and $122,653/QALY, respectively. The probabilities of the avelumab strategy and the PD-L1-guided strategy being cost-effective in the simultaneous competition of the three strategies were 38.49% and 48.82%. In patients with PD-L1-positive status, the avelumab strategy had an 87.51% probability of cost-effectiveness. The most influential parameter for the model was the cost of avelumab and pembrolizumab. CONCLUSIONS: This analysis demonstrated that maintenance therapy with avelumab plus BSC may be a cost-effective option for patients with advanced or metastatic urothelial carcinoma at a willingness-to-pay (WTP) threshold of $150,000/QALY, especially for patients with PD-L1-positive status.
