Tremelimumab and durvalumab with chemotherapy in first-line treatment for metastatic non-small cell lung cancer: a US-based cost-effectiveness analysis.

While the tremelimumab plus durvalumab combined with chemotherapy (T + D + CT) has shown promise in treating epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) wild-type metastatic non-small cell lung cancer (mNSCLC), particularly in patients with low or no programmed cell death ligand 1 (PD-L1) expression, the economic implications of its high cost remain poorly understood. This study fills a critical gap in knowledge by evaluating the cost-effectiveness of T + D + CT from a US health care perspective, offering valuable insights for clinical and policy decision-making. A 10-year Markov model was crafted to track the disease progression, survival, and treatment-related toxicities of a patient cohort with EGFR/ALK wild-type mNSCLC. Transition probabilities were derived from the POSEIDON trial, while health state utilities were obtained from the literature. Cost data, including drug acquisition and administration, subsequent anticancer therapies, and adverse event management were estimated using the Centers for Medicare and Medicaid Services and the Healthcare Cost and Utilization Project databases, with additional costs sourced from current literature. All cost and effectiveness measures were discounted at an annual rate of 3%. The model's robustness was assessed through deterministic sensitivity analysis (DSA), probabilistic sensitivity analysis (PSA), and scenario analysis. T + D + CT compared to chemotherapy alone yielded incremental cost-effectiveness ratios (ICERs) of $370,208 to $691,960 per quality-adjusted life-year (QALY) gained, exceeding the standard willingness-to-pay (WTP) threshold of $100,000 to $150,000 per QALY. Against durvalumab plus chemotherapy, T + D + CT was only cost-effective in all subgroups. DSA results for patients with PD-L1 expression <1% showed that the ICER for first-line T + D + CT remained above the WTP threshold range, even with substantial changes to model inputs. PSA revealed a higher likelihood of T + D + CT being cost-effective as WTP thresholds increased. Scenario analysis confirmed the study's primary findings, with the exception of a scenario where durvalumab was offered at no cost. The findings suggests that T + D + CT may not be a cost-effectiveness first-line treatment for EGFR/ALK wild-type mNSCLC in the US, given its high ICERs and limited cost-effectiveness in the majority of PD-L1 expression subgroups.

Zhao Z ，Zeng X ，Zhou Z ，Liu Q ... -  《-》

First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States.

Liu W ，Huo G ，Chen P 《Frontiers in Pharmacology》

Cost-effectiveness of durvalumab plus tremelimumab in combination with chemotherapy for the treatment of metastatic non-small-cell lung cancer from the US healthcare sector's and societal perspectives.

Gan Y ，Shi F ，Zhu H ，Li H ，Han S ，Li D ... -  《Frontiers in Pharmacology》

Biomarkers-Based Cost-Effectiveness of Toripalimab Plus Chemotherapy for Patients with Treatment-Naive Advanced Non-Small Cell Lung Cancer.

This study examined the cost-effectiveness of first-line toripalimab plus chemotherapy (TC) for patients with advanced non-small cell lung cancer (NSCLC), excluding patients with nonsquamous NSCLC and EGFR/ALK mutations. It further analyzed the cost-effectiveness of this strategy in biomarker-based subgroups, all within the context of the Chinese healthcare system. Eighteen Markov models with 21-day Markov cycle lengths and 30-year time horizons were constructed in this study. Clinical effectiveness data were derived from the CHOICE-01 trial. Health state utilities and costs data were obtained from various sources. The primary outputs were the calculation of incremental cost-effectiveness ratios (ICERs), which were then compared to a willingness-to-pay (WTP) threshold of $17,961 per quality-adjusted life-year (QALY). This comparison was used to determine the treatment that offered greater cost-effectiveness. To account for uncertainty in the model, sensitivity analyses were conducted. For the overall patient population, the estimated ICER between first-line TC and placebo plus chemotherapy (PC) was $9445/QALY, significantly lower than the WTP threshold used in the model. In subgroups based on pathologic types, first-line TC had an ICER of $16,757/QALY for patients with nonsquamous NSCLC, slightly below the WTP threshold; first-line TC demonstrated dominance in patients with squamous NSCLC, indicating both better effectiveness and lower costs compared to first-line PC. In biomarkers-based subgroups, first-line TC was dominant over first-line PC in the subgroups with programmed cell death ligand 1 (PD-L1) expression ≥ 50% and SMARCA4 mutations. Moreover, first-line TC had ICERs lower than the WTP threshold in other subgroups, except for the subgroup with RB1 mutations. Sensitivity analysis confirmed the robustness of these findings. From the perspective of the Chinese healthcare system, this study's findings suggested that first-line TC represents a cost-effective strategy for patients with advanced NSCLC. However, the cost-effectiveness of first-line TC varied across different subgroups when considering predictive biomarkers.

Zhang H ，Li L ，Feng L ，Zhou Z ，Zhang X ，Feng J ，Liu Q ... -  《-》

Cost-Effectiveness Analysis of Atezolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer With Different PD-L1 Expression Status.

Atezolizumab could significantly improve clinical outcomes and was associated with less toxicity compared with chemotherapy as the first-line treatment of PD-L1-selected patients with EGFR and ALK wild-type metastatic non-small-cell lung cancer (NSCLC). However, the economic outcomes remain unclear yet in China. This study aimed to investigate the cost-effectiveness of atezolizumab versus chemotherapy as first-line therapy for metastatic NSCLC with different PD-L1 expression status from the Chinese health sector perspective. A decision-analytic model was conducted to evaluate the economic outcomes for the first-line treatment of EGFR and ALK wild-type metastatic NSCLC with atezolizumab and chemotherapy in high PD-L1 expression, high or intermediate PD-L1 expression and any PD-L1 expression populations, respectively. The efficacy and safety data were obtained from the IMpower110 trial. Cost and utility values were gathered from the local charges and published literatures. Incremental cost-effectiveness ratio (ICER) was estimated. A scenario analysis for a patient assistance program (PAP) was conducted. One-way and probabilistic sensitivity analyses were performed to explore the robustness of the model results. Atezolizumab yielded additional 0.91 QALYs, 0.57 QALYs, 0.42 QALYs in comparison with chemotherapy, and the ICERs were $123,778.60/QALY, $142,827.19/QALY, $168,902.66/QALY in the high PD-L1 expression, high or intermediate PD-L1 expression, and any PD-L1 expression populations, respectively. When PAP was available, the ICERs were $52,414.63/QALY, $52,329.73/QALY, $61,189.66/QALY in the three categories of PD-L1 expression status populations, respectively. The ICERs were exceed the willingness-to-pay (WTP) threshold of $30,828/QALY (three times of per capita gross domestic product of China in 2019) in China. One-way sensitivity analyses suggested that the cost of atezolizumab played a vital role in the model outcomes, and the probabilistic sensitivity analyses showed atezolizumab was unlikely to be cost-effective at the WTP threshold regardless of PD-L1 expression status and whether the PAP was available or not. Atezolizumab as first-line treatment for PD-L1-selected metastatic NSCLC patients without EGFR mutations or ALK translocations is unlikely to be cost-effective compared with chemotherapy regardless of PD-L1 expression status in the Chinese context.

Liu G ，Kang S ，Wang X ，Shang F ... -  《-》