Wurcel Victoria, Scherrer Emilie, Aguiar-Ibanez Raquel, Altuna Juan Ignacio, Carabajal Fernando, Jain Shrishti, Baluni Gargi
MSD Argentina, Buenos Aires, Argentina.
Merck & Co., Inc, Kenilworth, NJ, USA.
Oncol Ther. 2021 Jun;9(1):167-185. doi: 10.1007/s40487-021-00142-8. Epub 2021 Feb 23.
The KEYNOTE-054 trial demonstrated that adjuvant pembrolizumab improves recurrence-free survival in completely resected stage III melanoma versus watchful waiting (hazard ratio [HR] = 0.57; 98.4% confidence interval [CI], 0.43-0.74). We evaluated the cost-effectiveness of pembrolizumab in Argentina, where watchful waiting is still widely used among these patients despite the high risk of recurrence with surgery alone.
A four-health state model was used (recurrence-free, locoregional recurrence [LR], distant metastases [DM], death). Lifetime medical costs to payers (72.08 Argentine pesos [AR$] = 1.00 U.S. dollar [USD]) and outcomes (3% annual discount) were assessed, together with incremental cost-effectiveness ratios (ICERs). First and LR→DM recurrences were modeled using KEYNOTE-054 and real-world data, respectively. No benefits of adjuvant treatment were assumed post-progression. Pre-DM and post-DM mortality was based on KEYNOTE-054 and on a network meta-analysis of advanced treatments expected in each arm, respectively. Utilities were derived from KEYNOTE-054 Euro-QoL data using an Argentinian algorithm, and from the literature. Public ex-factory drug prices were used.
Patients in the pembrolizumab and the watchful waiting arms accrued 8.78 and 5.83 quality-adjusted life-years (QALYs), 9.91 and 6.98 life-years, and costs of AR$12,698,595 (176,174 USD) and AR$11,967,717 (166,034 USD), respectively. The proportion of life-years accrued that were recurrence-free was 80.8% and 56.9% in the pembrolizumab and the watchful waiting arms, respectively. Pembrolizumab patients gained 2.94 life-years and 2.96 QALYs versus watchful waiting; the ICER per QALY was AR$247,094 (3428 USD). Recurrence rates and advanced melanoma treatments were the key drivers of the ICER. At a threshold of AR$1,445,325 (29,935 USD) per QALY, pembrolizumab had an 83.5% probability of being cost-effective versus watchful waiting.
Adjuvant pembrolizumab after complete resection of melanoma with node involvement is highly cost-effective relative to watchful waiting in Argentina, across disease stage subgroups and BRAF mutational status. This strongly supports its coverage and reimbursement across the entire health system.
KEYNOTE-054试验表明，与观察等待相比，辅助性帕博利珠单抗可改善完全切除的III期黑色素瘤患者的无复发生存期（风险比[HR]=0.57；98.4%置信区间[CI]，0.43 - 0.74）。我们评估了帕博利珠单抗在阿根廷的成本效益，尽管仅手术复发风险高，但观察等待在这些患者中仍被广泛使用。
使用四健康状态模型（无复发、局部区域复发[LR]、远处转移[DM]、死亡）。评估了支付方的终身医疗成本（72.08阿根廷比索[AR$]=1.00美元[USD]）和结局（3%年度贴现率），以及增量成本效益比（ICER）。首次复发和LR→DM复发分别使用KEYNOTE-054和真实世界数据进行建模。进展后不假设辅助治疗的益处。DM前和DM后的死亡率分别基于KEYNOTE-054和各治疗组预期的晚期治疗的网络荟萃分析。效用值分别使用阿根廷算法从KEYNOTE-054欧洲五维度健康量表数据和文献中得出。使用药品出厂价。
帕博利珠单抗组和观察等待组患者分别获得8.78和5.83个质量调整生命年（QALY）、9.91和6.98个生命年，成本分别为12,698,595阿根廷比索（176,174美元）和11,967,717阿根廷比索（166,034美元）。帕博利珠单抗组和观察等待组无复发生命年的比例分别为80.8%和56.9%。与观察等待相比，帕博利珠单抗组患者多获得2.94个生命年和2.96个QALY；每QALY的ICER为247,094阿根廷比索（3428美元）。复发率和晚期黑色素瘤治疗是ICER的关键驱动因素。在每QALY阈值为1,445,325阿根廷比索（29,935美元）时，与观察等待相比，帕博利珠单抗具有成本效益的概率为83.5%。
在阿根廷，对于有淋巴结受累的黑色素瘤患者，完全切除后辅助使用帕博利珠单抗相对于观察等待具有很高的成本效益，适用于所有疾病阶段亚组和BRAF突变状态。这有力地支持了其在整个医疗系统中的覆盖和报销。
