Atezolizumab and durvalumab, when used in combination with chemotherapy as first-line treatments for extensive-disease small-cell lung cancer (ED-SCLC) in Japan, are not cost-effective, according to a recent study. The analysis, which adopted the perspective of Japanese medical insurance payers, compared the cost-effectiveness of atezolizumab plus carboplatin plus etoposide (ACE) and durvalumab plus carboplatin plus etoposide (DCE) against carboplatin plus etoposide (CE) alone.
The study, utilizing a partitioned survival model based on data from the IMpower 133 and CASPIAN trials, revealed that the incremental cost-effectiveness ratios (ICERs) for ACE and DCE were approximately 35 million JPY and 37 million JPY, respectively. These values significantly exceed the commonly used willingness-to-pay threshold of 15 million JPY (approximately 114,068 USD) per quality-adjusted life year (QALY) in Japan.
Economic Burden of ED-SCLC Treatment
Lung cancer remains a leading cause of cancer-related deaths worldwide, with small-cell lung cancer (SCLC) accounting for 10-15% of all lung cancer cases. ED-SCLC, characterized by early and extensive metastasis, carries a particularly poor prognosis. While the combination of platinum-based chemotherapy with etoposide has been the standard of care, recent studies have demonstrated the efficacy of immune checkpoint inhibitors (ICIs) like atezolizumab and durvalumab in improving overall survival (OS).
However, the high cost of these ICIs raises concerns about their economic impact, particularly within the Japanese universal health insurance system. This study aimed to address this concern by comparing the cost-effectiveness of atezolizumab and durvalumab as first-line treatments for ED-SCLC in Japan.
Methodology and Findings
The researchers constructed a partitioned survival model to simulate the progression of ED-SCLC patients under different treatment regimens. The model incorporated data on overall survival (OS) and progression-free survival (PFS) from the IMpower 133 and CASPIAN trials. Direct medical costs, including medication expenses, supportive care, management of treatment-related adverse events, and end-of-life care, were considered from the perspective of Japanese medical insurance payers.
Sensitivity analyses were conducted to assess the robustness of the findings to variations in key parameters, such as drug prices, utility values, and adverse event rates. The results consistently showed that the ICERs for ACE and DCE remained significantly above the cost-effectiveness threshold, even under various scenarios.
Implications and Comparison with Other Studies
The study's findings align with previous cost-effectiveness analyses conducted in the USA and China, which also concluded that atezolizumab and durvalumab combination treatments are not cost-effective compared to chemotherapy alone for ED-SCLC. For example, studies by Zhou et al. and Li et al. reported ICERs for ACE ranging from 489,013 to 528,810 USD/QALY in the US and Chinese healthcare systems, respectively. Zhang et al. found an ICER of 355,448 USD/QALY for DCE in the US setting.
"The sensitivity analysis revealed the need for significant price reductions, estimating acceptable pricing for atezolizumab and durvalumab to be 10% and 5% of their current prices, respectively. However, such reductions are not feasible," the authors noted.
Limitations and Future Directions
The authors acknowledged several limitations of their study, including the extrapolation of survival curves beyond the clinical trial observation period and the reliance on utility values derived from studies conducted outside of Japan. Additionally, the cost data following disease progression were based on the JMDC database, which may not fully represent the Japanese health insurance system overall.
Despite these limitations, the study provides valuable insights into the economic implications of using atezolizumab and durvalumab in the treatment of ED-SCLC in Japan. The findings suggest that alternative strategies, such as exploring smaller dosages, longer intervals between treatments, and targeting more effective subpopulations, may be necessary to improve the cost-effectiveness of these therapies.
