Melanoma Institute Australia, The University of Sydney, Sydney; Faculty of Medicine and Health, The University of Sydney, Sydney; Royal North Shore Hospital, Sydney; Mater Hospital, Sydney.
Melanoma Institute Australia, The University of Sydney, Sydney; Faculty of Medicine and Health, The University of Sydney, Sydney.
Ann Oncol. 2024 Aug;35(8):739-746. doi: 10.1016/j.annonc.2024.05.002. Epub 2024 May 14.
Neoadjuvant dabrafenib plus trametinib has a high pathological response rate and impressive short-term survival in patients with resectable stage III melanoma. We report 5-year outcomes from the phase II NeoCombi trial.
NeoCombi (NCT01972347) was a single-arm, open-label, single-centre, phase II trial. Eligible patients were adults (aged ≥18 years) with histologically confirmed, resectable, RECIST-measurable, American Joint Committee on Cancer seventh edition clinical stage IIIB-C BRAF V600E/K-mutant melanoma and Eastern Cooperative Oncology Group performance status ≤1. Patients received 52 weeks of treatment with dabrafenib 150 mg (orally twice per day) plus trametinib 2 mg (orally once per day), with complete resection of the pre-therapy tumour bed at week 12.
Between 20 August 2014 and 19 April 2017, 35 patients were enrolled. At data cut-off (17 August 2021), the median follow-up was 60 months [95% confidence interval (CI) 56-72 months]. Overall, 21 of 35 (60%) patients recurred, including 12 (57%) with first recurrence in locoregional sites (followed by later distant recurrence in 6) and 9 (43%) with first recurrence in distant sites, including 3 in the brain. Most recurrences occurred within 2 years, with no recurrences beyond 3 years. At 5 years, recurrence-free survival (RFS) was 40% (95% CI 27% to 60%), distant metastasis-free survival (DMFS) was 57% (95% CI 42% to 76%), and overall survival was 80% (95% CI 67% to 94%). Five-year survival outcomes were stratified by pathological response: RFS was 53% with pathological complete response (pCR) versus 28% with non-pCR (P = 0.087), DMFS was 59% versus 55% (P = 0.647), and overall survival was 88% versus 71% (P = 0.205), respectively.
Neoadjuvant dabrafenib plus trametinib has high pathological response rates in clinical stage III melanoma, but low rates of RFS, similar to those achieved with adjuvant targeted therapy alone. Patients with a pCR to dabrafenib plus trametinib still had a high risk of recurrence, unlike that seen with immunotherapy where recurrences are rare.
新辅助达拉非尼联合曲美替尼在可切除 III 期黑色素瘤患者中具有高病理缓解率和令人印象深刻的短期生存率。我们报告了 II 期 NeoCombi 试验的 5 年结果。
NeoCombi（NCT01972347）是一项单臂、开放标签、单中心、II 期试验。符合条件的患者为组织学证实的、可切除的、RECIST 可测量的、美国癌症联合委员会第七版临床 IIIB-C BRAF V600E/K 突变黑色素瘤和东部合作肿瘤学组表现状态≤1 的成年患者（年龄≥18 岁）。患者接受 52 周的达拉非尼 150mg（每日两次口服）联合曲美替尼 2mg（每日一次口服）治疗，在第 12 周时完全切除术前肿瘤床。
2014 年 8 月 20 日至 2017 年 4 月 19 日期间，共纳入 35 例患者。数据截止日期（2021 年 8 月 17 日）时，中位随访时间为 60 个月[95%置信区间（CI）56-72 个月]。总体而言，35 例患者中有 21 例（60%）复发，包括 12 例（57%）首次局部复发（随后 6 例远处复发）和 9 例（43%）首次远处复发，包括 3 例脑转移。大多数复发发生在 2 年内，3 年后无复发。5 年时，无复发生存率（RFS）为 40%（95%CI 27%-60%），无远处转移生存（DMFS）率为 57%（95%CI 42%-76%），总生存率为 80%（95%CI 67%-94%）。根据病理反应对 5 年生存结果进行分层：病理完全缓解（pCR）的 RFS 为 53%，非 pCR 为 28%（P=0.087），DMFS 为 59%和 55%（P=0.647），总生存率为 88%和 71%（P=0.205）。
新辅助达拉非尼联合曲美替尼在 III 期黑色素瘤中具有较高的病理缓解率，但 RFS 率较低，与单独接受辅助靶向治疗相似。达拉非尼联合曲美替尼 pCR 的患者仍有较高的复发风险，与免疫治疗不同，免疫治疗后复发罕见。
