Ma Emily Z, Terhune Julia H, Zafari Zafar, Blackburn Kyle W, Olson John A, Mullins C Daniel, Hu Yinin
Department of Surgery/Division of General and Oncologic Surgery (Ma, Terhune, Zafari, Blackburn, Olson, Hu), University of Maryland Medical Center, Baltimore, MD.
Department of Pharmaceutical Health Services Research (Mullins), University of Maryland Medical Center, Baltimore, MD.
J Am Coll Surg. 2022 Apr 1;234(4):521-528. doi: 10.1097/XCS.0000000000000088.
Adjuvant therapy for most sentinel-node-positive (stage IIIA) melanoma may have limited clinical benefit for older patients given the competing risk of non-cancer death. The objective of this study is to model the clinical effect and cost of adjuvant therapy in stage IIIA melanoma across age groups.
A Markov decision analysis model simulated the overall survival of patients with resected stage IIIA melanoma treated with adjuvant therapy vs observation. In the adjuvant approach, patients are modeled to receive adjuvant pembrolizumab (BRAF wild type) or dabrafenib/trametinib (BRAF mutant). In the observation approach, treatment is deferred until recurrence. Transition variables were derived from landmark randomized trials in adjuvant and salvage therapy. The model was analyzed for age groups spanning 40 to 89 years. The primary outcome was the number needed to treat (NNT) to prevent one melanoma-related death at 10 years. Cost per mortality avoided was estimated using Medicare reimbursement rates.
Projections for NNT among BRAF wild type patients increased by age from 14.71 (age 40 to 44) to 142.86 (age 85 to 89), with patients in cohorts over the age of 75 having an NNT over 25. The cost per mortality avoided ranged from $2.75 million (M) (age 40 to 44) to $27.57M (age 85 to 89). Corresponding values for BRAF mutant patients were as follows: NNT 18.18 to 333.33; cost per mortality avoided ranged from $2.75M to $54.70M.
Universal adjuvant therapy for stage IIIA melanoma is costly and provides limited clinical benefit in patients older than 75 years.
鉴于存在非癌症死亡的竞争风险，对于大多数前哨淋巴结阳性（IIIA期）黑色素瘤患者而言，辅助治疗对老年患者的临床益处可能有限。本研究的目的是模拟IIIA期黑色素瘤辅助治疗在不同年龄组中的临床效果和成本。
一个马尔可夫决策分析模型模拟了接受辅助治疗与观察的IIIA期黑色素瘤切除患者的总生存期。在辅助治疗方法中，患者被模拟为接受辅助派姆单抗（BRAF野生型）或达拉非尼/曲美替尼（BRAF突变型）治疗。在观察方法中，治疗推迟至复发。转移变量源自辅助和挽救治疗的标志性随机试验。该模型针对40至89岁的年龄组进行了分析。主要结局是在10年时预防一例黑色素瘤相关死亡所需的治疗人数（NNT）。使用医疗保险报销率估算避免每例死亡的成本。
BRAF野生型患者的NNT预测值随年龄增长从14.71（40至44岁）增至142.86（85至89岁），75岁以上队列的患者NNT超过25。避免每例死亡的成本从275万美元（40至44岁）至2757万美元（85至89岁）不等。BRAF突变型患者的相应值如下：NNT为18.18至333.33；避免每例死亡的成本从275万美元至5470万美元不等。
IIIA期黑色素瘤的普遍辅助治疗成本高昂，且对75岁以上患者的临床益处有限。
