Herbreteau Guillaume, Langlais Alexandra, Greillier Laurent, Audigier-Valette Clarisse, Uwer Lionel, Hureaux José, Moro-Sibilot Denis, Guisier Florian, Carmier Delphine, Madelaine Jeannick, Otto Josiane, Souquet Pierre-Jean, Gounant Valérie, Merle Patrick, Molinier Olivier, Renault Aldo, Rabeau Audrey, Morin Franck, Denis Marc G, Pujol Jean-Louis
Department of Biochemistry, Nantes University Hospital, 9 quai Moncousu, 44093 Nantes, France.
IFCT Intergroupe Francophone de Cancérologie Thoracique, 10 Rue de la Grange Batelière, 75009 Paris, France.
J Clin Med. 2020 Nov 27;9(12):3861. doi: 10.3390/jcm9123861.
The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab.
68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the , and genes. ctDNA was detectable when at least one somatic mutation was identified, and its relative abundance was quantified by the variant allele fraction (VAF) of the most represented mutation.
We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49; 65.3%) and RB1 (25/49; 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm.
ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.
IFCT - 1603试验评估了阿替利珠单抗在小细胞肺癌（SCLC）中的疗效。本研究的目的是确定在治疗开始时前瞻性收集的循环肿瘤DNA（ctDNA）是否与SCLC的预后相关，以及它是否能识别出从阿替利珠单抗治疗中获益的患者。
本研究纳入68例患者：46例接受阿替利珠单抗治疗，22例接受传统化疗。从血浆中提取循环DNA，采用二代测序（NGS）检测 、 和 基因中的突变。当鉴定出至少一个体细胞突变时，ctDNA可检测到，其相对丰度通过最常见突变的变异等位基因分数（VAF）进行定量。
我们发现49/68例患者（70.6%）基线ctDNA可检测到。最常鉴定出的突变是TP53（32/49；65.3%）和RB1（25/49；51.0%）。无论治疗性质如何，ctDNA可检测到的患者在第6周时的疾病控制率显著低于ctDNA不可检测的患者。ctDNA的检测与较差的总生存期预后相关。相对丰度大于中位数的ctDNA检测与较差的总生存期（OS）和无进展生存期（PFS）显著相关。有趣的是，ctDNA水平低的患者接受阿替利珠单抗治疗时总生存期（OS）的获益比接受化疗的患者更明显。在相对ctDNA丰度低于中位数的患者中，接受阿替利珠单抗治疗的患者总生存期往往高于化疗组。
ctDNA与接受二线免疫治疗的SCLC患者的预后密切相关。对其进行分析似乎对未来的SCLC临床试验是合理的。
