Czarnecka Anna M, Ostaszewski Krzysztof, Błoński Piotr J, Szumera-Ciećkiewicz Anna, Świtaj Tomasz, Kozak Katarzyna, Koseła-Patreczyk Hanna, Rogala Paweł, Kalinowska Iwona, Zaborowski Konrad, Krotewicz Maria, Borkowska Aneta, Rutkowski Piotr
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland.
Cancer. 2024 Oct 15;130(20):3463-3472. doi: 10.1002/cncr.35425. Epub 2024 Jun 6.
Neoadjuvant-adjuvant therapy for locally advanced or potentially resectable metastatic melanoma was expected to improve operability and clinical outcomes over upfront surgery and adjuvant treatment only.
Forty-seven consecutive patients were treated with neoadjuvant-adjuvant BRAF inhibitors (BRAFi)/MEK inhibitors (MEKi) and surgery.
Twelve (26%) patients achieved a pathological complete response and 10 (21%) patients achieved a near-complete response. In the whole group, median recurrence-free survival was 19.4 months and median distant metastasis-free survival (mDMFS) was 21.9 months. In patients with a pathological complete response (pCR)/near-pCR median recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were significantly longer than in patients with minor pathological response with hazard ratio (HR) = 0.37 (p = .005) for RFS and HR = 0.33 (p = .002) for DMFS. After median follow-up of 52.5 months, median progression-free survival since BRAFi/MEKi therapy initiation was 25.1 months. The median time-to-treatment-failure since initiation of neoadjuvant therapy was 22.2 months and was significantly longer in patients with pCR/near-pCR (HR = 0.45; p = .022). Neoadjuvant therapy did not result in any new specific complications of surgery. After 48 months, RFS and overall survival were 36.3% and 64.8% or 20% and 37.4% in patients with pCR/near-pCR and pathological partial response/pathological nonresponse, respectively.
The authors confirmed that BRAFi/MEKi combination is an effective and safe regimen in the perioperative treatment of stage III/IV melanoma. Major pathological response to neoadjuvant treatment is a surrogate marker of recurrence including DMFS in these patients.
Our study presents a large comprehensive analysis of neoadjuvant-adjuvant systemic therapy in patients diagnosed with marginally resectable stage III or IV melanoma. Neoadjuvant therapy effectively reduced the volume of the disease, which facilitated subsequent surgical resection. After median follow-up of 52.5 months, median progression-free survival since therapy initiation was 25.1 months. Twelve patients had complete pathological response and 10 patients had a near-complete pathological response-and together they had median recurrence-free survival and distant metastasis-free survival significantly longer than in patients with pathological partial response or nonresponse. Complete/near-complete pathological response to neoadjuvant treatment is a surrogate marker of recurrence-free, including distant metastasis-free, survival in these patients.
对于局部晚期或潜在可切除的转移性黑色素瘤，新辅助 - 辅助治疗有望比单纯的 upfront 手术和辅助治疗提高手术可操作性和临床结局。
连续 47 例患者接受新辅助 - 辅助 BRAF 抑制剂（BRAFi）/MEK 抑制剂（MEKi）及手术治疗。
12 例（26%）患者达到病理完全缓解，10 例（21%）患者达到接近完全缓解。在整个队列中，无复发生存期的中位数为 19.4 个月，远处转移无进展生存期（mDMFS）的中位数为 21.9 个月。在病理完全缓解（pCR）/接近 pCR 的患者中，无复发生存期（RFS）和远处转移无进展生存期（DMFS）显著长于病理反应较小的患者，RFS 的风险比（HR）=0.37（p = 0.005），DMFS 的 HR = 0.33（p = 0.002）。中位随访 52.5 个月后，自 BRAFi/MEKi 治疗开始后的无进展生存期中位数为 25.1 个月。自新辅助治疗开始至治疗失败的中位时间为 22.2 个月，在 pCR/接近 pCR 的患者中显著更长（HR = 0.45；p = 0.022）。新辅助治疗未导致任何新的手术特异性并发症。48 个月后，pCR/接近 pCR 和病理部分缓解/病理无反应的患者的 RFS 和总生存率分别为 36.3%和 64.8%或 20%和 37.4%。
作者证实 BRAFi/MEKi 联合方案在 III/IV 期黑色素瘤围手术期治疗中是一种有效且安全的方案。新辅助治疗的主要病理反应是这些患者复发（包括 DMFS）的替代标志物。
我们的研究对诊断为边缘可切除的 III 期或 IV 期黑色素瘤患者的新辅助 - 辅助全身治疗进行了大规模综合分析。新辅助治疗有效减少了疾病体积，便于后续手术切除。中位随访 52.5 个月后，自治疗开始后的无进展生存期中位数为 25.1 个月。12 例患者有完全病理反应，10 例患者有接近完全病理反应，他们的无复发生存期和远处转移无进展生存期的中位数显著长于病理部分缓解或无反应的患者。新辅助治疗的完全/接近完全病理反应是这些患者无复发（包括无远处转移）生存的替代标志物。
