Treatment Outcomes and Clinical Characteristics of Patients with KRAS-G12C-Mutant Non-Small Cell Lung Cancer.
Treatment Outcomes and Clinical Characteristics of Patients with KRAS-G12C-Mutant Non-Small Cell Lung Cancer.
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KRAS-G12 C突变型非小细胞肺癌患者的治疗结局和临床特征
DOI：
10.1158/1078-0432.ccr-20-4023
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发表时间：
2021-04-15
期刊：
影响因子：
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通讯作者：
Riely GJ
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文献类型：
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作者：
Arbour KC;Rizvi H;Plodkowski AJ;Hellmann MD;Knezevic A;Heller G;Yu HA;Ladanyi M;Kris MG;Arcila ME;Rudin CM;Lito P;Riely GJ
在约30%的NSCLC患者中发现了KRAS突变。KRAS G12C的新型直接抑制剂已在早期临床试验中显示出活性。我们假设KRAS G12C突变患者可能具有不同的临床特征和对治疗的反应。通过常规的下一代测序，我们确定了2014 - 2018年在Memorial Sloan Kettering癌症中心接受治疗的KRAS突变型NSCLC患者，并审查了肿瘤特征、总生存期和治疗结局。我们确定了1194例KRAS突变型NSCLC患者，包括770例复发或转移性疾病。KRAS G12C突变占46%，KRAS非G12C突变占54%。KRAS G12 C患者的肿瘤突变负荷较高（中位8.8 mut/Mb vs 7.0 mut/Mb，p = 0.006），中位PD-L1表达较高（5% vs 1%）。STK11（28%对29%）和KEAP 1（23%对24%）的共突变模式相似。KRAS G12C（13.4个月）和KRAS非G12C突变（13.1个月，p = 0.96）的诊断后中位总生存期相似。在PD-L1 ≥ 50%的患者中，KRAS G12 C突变患者接受免疫检查点抑制剂单药治疗的缓解率无显著差异（40% vs 58%，p = 0.07）。我们提供了一个大系列的KRAS G12C突变型NSCLC患者的结局数据，这些患者接受了可用的治疗，证明可用治疗的缓解和获益持续时间与KRAS非G12C突变患者相似。将新的靶向治疗纳入当前治疗模式的策略需要考虑携带KRAS G12C突变的患者的特定结局。
KRAS mutations are identified in ~30% of patients with NSCLC. Novel direct inhibitors of KRAS G12C have shown activity in early phase clinical trials. We hypothesized that patients with KRAS G12C mutations may have distinct clinical characteristics and responses to therapies. Through routine next-generation sequencing, we identified patients with KRAS-mutant NSCLC treated at Memorial Sloan Kettering Cancer Center from 2014–2018 and reviewed tumor characteristics, overall survival, and treatment outcomes. We identified 1194 patients with KRAS-mutant NSCLC, including 770 with recurrent or metastatic disease. KRAS G12C mutations were present in 46% and KRAS non-G12C mutations in 54%. Patients with KRAS G12C had a higher tumor mutation burden (median 8.8 mut/Mb vs 7.0 mut/Mb, p=0.006) and higher median PD-L1 expression (5% vs 1%). The co-mutation patterns of STK11 (28% vs 29%) and KEAP1 (23% vs 24%) were similar. The median overall survivals from diagnosis were similar for KRAS G12C (13.4 months) and KRAS non-G12C mutations (13.1 months, p=0.96). In patients with PD-L1 ≥50%, there was not a significant difference in response rate with single-agent immune checkpoint inhibitor for patients with KRAS G12C mutations (40% vs 58%, p=0.07). We provide outcome data for a large series of patients with KRAS G12C-mutant NSCLC with available therapies, demonstrating that responses and duration of benefit with available therapies are similar to those seen in patients with KRAS non-G12C mutations. Strategies to incorporate new targeted therapies into the current treatment paradigm will need to consider outcomes specific to patients harboring KRAS G12C mutations.