Frequency of S492R mutations in the epidermal growth factor receptor: analysis of plasma DNA from patients with metastatic colorectal cancer treated with panitumumab or cetuximab monotherapy.
Frequency of S492R mutations in the epidermal growth factor receptor: analysis of plasma DNA from patients with metastatic colorectal cancer treated with panitumumab or cetuximab monotherapy.
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DOI：
10.1080/15384047.2020.1798695
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发表时间：
2020-10-02
影响因子：
3.6
通讯作者：
Peeters M
中科院分区：
文献类型：
--
作者：
Price T;Ang A;Boedigheimer M;Kim TW;Li J;Cascinu S;Ruff P;Satya Suresh A;Thomas A;Tjulandin S;Peeters M
针对表皮生长因子受体（EGFR）的抗体、帕尼单抗（一种全人源单克隆抗体）和西妥昔单抗（一种人/小鼠嵌合单克隆抗体）已在转移性结直肠癌（mCRC）中显示出临床疗效。在III期非劣效性ASPECCT（ClinicalTrials.gov，NCT 01001377）研究中，帕尼单抗被证明非劣效于西妥昔单抗，并为化疗难治性野生型KRAS外显子2 mCRC患者提供了相似的总生存期获益。然而，一些患者最终对抗EGFR治疗产生耐药性。EGFR p.S492R突变先前被确定为赋予对西妥昔单抗的耐药性，但不赋予对帕尼单抗的耐药性。这项生物标志物研究分析了基线和治疗后收集的ASPECCT血浆样本。基线时未发现EGFR p.S492R突变;然而，治疗后，在接受帕尼单抗治疗的患者中检测到EGFR p.S492R突变的比例为1%，而在接受西妥昔单抗治疗的患者中为16%，这支持了在大规模人群中，西妥昔单抗比帕尼单抗更可能诱导该突变。然而，在西妥昔单抗组或总体人群中，野生型患者与S492 R突变患者之间的无进展生存期或总生存期无显著差异。这些结果可能支持基于出现EGFR突变的小患者亚组的靶向治疗，并为在发生耐药的患者中使用不同的抗EGFR药物进行再激发提供了分子依据。需要前瞻性研究来评价帕尼单抗在EGFR p.S492R突变人群中的疗效。
Antibodies against epidermal growth factor receptor (EGFR), panitumumab, a fully human monoclonal antibody, and cetuximab, a human/mouse chimeric monoclonal antibody, have shown clinical efficacy in metastatic colorectal cancer (mCRC). In the phase 3 noninferiority ASPECCT (ClinicalTrials.gov, NCT01001377) study, panitumumab was demonstrated to be noninferior to cetuximab and provided a similar overall survival benefit for patients with chemotherapy-refractory wild-type KRAS exon 2 mCRC. However, some patients eventually develop resistance to anti-EGFR therapy. EGFR p.S492R mutation was previously identified as conferring resistance to cetuximab, but not to panitumumab. This biomarker study analyzed plasma samples from ASPECCT collected at both baseline and posttreatment. No EGFR p.S492R mutations were identified at baseline; however, after treatment the EGFR p.S492R mutation was detected in 1% of patients treated with panitumumab versus 16% of those treated with cetuximab, supporting that, in a large population, this mutation is more likely to be induced by cetuximab than by panitumumab. There were, however, no significant differences in progression-free survival or overall survival between patients who were wild-type compared with those with the S492R mutation within the cetuximab arm or the overall population. These results may support targeting treatment to small patient subgroups based on the presence of emerging EGFR mutations and provide a molecular rationale for rechallenging with a different anti-EGFR agent in patients who develop resistance. Prospective studies are needed to evaluate the efficacy of panitumumab in the EGFR p.S492R mutant population.
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影响因子：
11.5
作者：
Peeters, Marc;Price, Timothy;Ang, Agnes
通讯作者：
Ang, Agnes
影响因子：
11.5
作者：
Taniguchi, Kazuya;Uchida, Junji;Kato, Kikuya
通讯作者：
Kato, Kikuya
DOI：
10.1158/1078-0432.ccr-11-2696
发表时间：
2012-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Higgins MJ;Jelovac D;Barnathan E;Blair B;Slater S;Powers P;Zorzi J;Jeter SC;Oliver GR;Fetting J;Emens L;Riley C;Stearns V;Diehl F;Angenendt P;Huang P;Cope L;Argani P;Murphy KM;Bachman KE;Greshock J;Wolff AC;Park BH
通讯作者：
Park BH
影响因子：
3.6
作者：
Pietrantonio, Filippo;Perrone, Federica;de Braud, Filippo
通讯作者：
de Braud, Filippo
影响因子：
--
作者：
Wang R;Li X;Zhang H;Wang K;He J
通讯作者：
He J