BRAF + MEK inhibition is preferentially applied as first-line therapy in BRAF V600-mutated melanoma patients with unfavourable prognostic features, due to the ability of targeted therapy (TT) to induce rapid symptom control, decrease tumour burden and normalize lactate dehydrogenase (LDH) levels. In addition, short-term TT transiently increases tumour antigen presentation and tumour influx of T cells. Therefore, it might be favourable to switch TT to checkpoint inhibition (CPI) before progression (PD). We retrospectively analysed melanoma patients treated first line with TT (TT1) and who subsequently switched to CPI during response to TT (sDR group) or at progression upon TT (sPD group). We identified 74 patients (n = 37 sDR group and n = 37 sPD group). ORR to CPI was 27.0% in the sDR group versus 24.3% in the sPD group (p = .790). Median was PFS 2.5 months versus 1.2 months (p = .145), and median OS was 30.6 versus 14.1 months (p = .007). After adjusting for baseline differences and known prognostic factors, hazard ratios (HRs) favouring sDR were 0.89 for PFS upon CPI (p = .956) and 0.48 for OS (p = .055). Thus, patients switching to CPI during ongoing clinical benefit from TT do not have an inferior outcome. Due to baseline imbalances and small patient population, a favourable trend for the sDR group can be hypothesized only.

中文翻译：

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在进行靶向治疗后，在进展时间或正在进行的反应期间切换至检查点抑制：BRAF突变的黑色素瘤患者的回顾性单中心经验。

由于靶向治疗（TT）具有诱导快速症状控制，减轻肿瘤负担并使乳酸脱氢酶（LDH）正常化的能力，因此BRAF + MEK抑制优先用于具有不良预后特征的BRAF V600突变的黑色素瘤患者的一线治疗。水平。另外，短期TT短暂增加肿瘤抗原呈递和T细胞的肿瘤流入。因此，在进展（PD）之前将TT切换到检查点抑制（CPI）可能是有利的。我们回顾性分析了一线用TT治疗的黑色素瘤患者（TT1），随后在对TT的反应期间（sDR组）或在TT进展时（sPD组）改用CPI。我们确定了74例患者（n = 37 sDR组和n = 37 sPD组）。sDR组的CPI的ORR为27.0％，而sPD组的为24.3％（p = .790）。中位值是PFS 2.5个月对1.2个月（p = .145），中位OS​​是30.6对14.1个月（p = .007）。在调整了基线差异和已知的预后因素后，CPI的PFS危险比（HRs）为0.89（p = .956），OS为0.48（p = .055）。因此，在持续的TT临床获益期间转用CPI的患者预后并不差。由于基线失衡和患者人数少，因此只能假设sDR组有一个有利的趋势。在持续进行TT的临床获益期间改用CPI的患者预后并不差。由于基线失衡和患者人数少，因此只能假设sDR组有有利趋势。在持续进行TT的临床获益期间改用CPI的患者预后并不差。由于基线失衡和患者人数少，因此只能假设sDR组有有利趋势。