Tumor mutation burden as a biomarker for lung cancer patients treated with pemetrexed and cisplatin (the JIPANG-TR).
Tumor mutation burden as a biomarker for lung cancer patients treated with pemetrexed and cisplatin (the JIPANG-TR).
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DOI：
10.1111/cas.14730
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发表时间：
2021-01
期刊：
影响因子：
5.7
通讯作者：
Nishio K
中科院分区：
文献类型：
--
作者：
Sakai K;Tsuboi M;Kenmotsu H;Yamanaka T;Takahashi T;Goto K;Daga H;Ohira T;Ueno T;Aoki T;Nakagawa K;Yamazaki K;Hosomi Y;Kawaguchi K;Okumura N;Takiguchi Y;Sekine A;Haruki T;Yamamoto H;Sato Y;Akamatsu H;Seto T;Saeki S;Sugio K;Nishio M;Okabe K;Yamamoto N;Nishio K
JIPANG研究是培美曲塞/顺铂(Pem/cis)与长春瑞滨/顺铂(VNR/cis)治疗完全切除的II-IIIA期非鳞状非小细胞肺癌(NS-NSCLC)的随机III期研究。这项研究没有达到主要终点(无复发生存期，RFS)，但Pem/cis的疗效与VNR/cis相似，耐受性更好。肿瘤突变负荷(TMB)被认为具有免疫检查点抑制剂的预测价值。然而，TMB与细胞毒化疗的相关性仍不清楚。本探索性研究旨在探讨肿瘤突变与PEM/Cis临床结局的关系。取自患者的福尔马林固定、石蜡包埋的肿瘤组织(n=389)。通过靶向深度测序分析组织DNA的突变情况。374例NS-NSCLC中，表皮生长因子受体(EGFR)突变频率较高(139/374)。没有任何EGFR突变的患者在Pem/cis臂的RFS比VNR/cis臂的RFS长。高TMB(≥12-16MUT/Mb)患者的PEM/CIS倾向于改善存活率。在野生型EGFR患者中，tmb和≥为12 MUT/Mb与Pem/cis和vnr/cis的RFS改善显著相关(未达到52.5个月；危险比(HR)0.477)。可以认为，在NS-NSCLC中，TMB可以预测Pem/cis与VNR/cis对RFS的益处。还需要进一步的研究来确定TMB和EGFR突变状态是否可以作为预测生物标记物。肿瘤突变负荷(TMB)是免疫检查点抑制治疗的预测指标。当结合EGFR突变状态时，TMB可作为非鳞状非小细胞肺癌患者术后培美曲塞联合顺铂辅助化疗的预测生物标志物。个性化辅助治疗将继续推进。
The JIPANG study is a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine/cisplatin (Vnr/Cis) for completely resected stage II‐IIIA non‐squamous non‐small cell lung cancer (Ns‐NSCLC). This study did not meet the primary endpoint (recurrence‐free survival, RFS) but Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability. Tumor mutation burden (TMB) is thought to have a predictive value of immune checkpoint inhibitors. However, the relevance of TMB to cytotoxic chemotherapy remains unknown. This exploratory study investigates the relationship between tumor mutation profiles and clinical outcome of Pem/Cis. Formalin‐fixed, paraffin‐embedded tumor tissues (n = 389) were obtained from the patients. Mutation status of tissue DNA was analyzed by targeted deep sequencing. Epidermal growth factor receptor (EGFR) mutations were detected frequently in Ns‐NSCLC (139/374). Patients without any EGFR mutations experienced longer RFS in the Pem/Cis arm versus Vnr/Cis arms. Pem/Cis in patients with high TMB (≥12‐16 mut/Mb) tended to have improved survival. In patients with wild‐type EGFR, TMB ≥ 12 mut/Mb was significantly associated with improved RFS with Pem/Cis versus Vnr/Cis (not reached vs 52.5 months; hazard ratio (HR) 0.477). It could be proposed that TMB was predictive of RFS benefit with Pem/Cis versus Vnr/Cis in Ns‐NSCLC. Further investigation is required to determine whether TMB combined with EGFR mutation status could be used as a predictive biomarker. Tumor mutation burden (TMB) is a predictor of immune checkpoint inhibition therapy. When combined with EGFR mutation status, TMB could be a predictive biomarker of postoperative adjuvant chemotherapy with pemetrexed plus cisplatin for patients with non‐squamous non‐small cell lung cancer. Personalized adjuvant therapy will continue to advance.
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影响因子：
4
作者：
Chaudhary, Ruchi;Quagliata, Luca;Hyland, Fiona
通讯作者：
Hyland, Fiona
影响因子：
45.3
作者：
Pignon, Jean-Pierre;Tribodet, Helene;Le Chevalier, Thierry
通讯作者：
Le Chevalier, Thierry
影响因子：
64.5
作者：
Rooney MS;Shukla SA;Wu CJ;Getz G;Hacohen N
通讯作者：
Hacohen N
影响因子：
3.1
作者：
Kano, Y;Akutsu, M;Furukawa, Y
通讯作者：
Furukawa, Y
DOI：
10.1056/nejmoa1801946
发表时间：
2018-05-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hellmann MD;Ciuleanu TE;Pluzanski A;Lee JS;Otterson GA;Audigier-Valette C;Minenza E;Linardou H;Burgers S;Salman P;Borghaei H;Ramalingam SS;Brahmer J;Reck M;O'Byrne KJ;Geese WJ;Green G;Chang H;Szustakowski J;Bhagavatheeswaran P;Healey D;Fu Y;Nathan F;Paz-Ares L
通讯作者：
Paz-Ares L