Circulating Tumor DNA as a Predictive Biomarker for Clinical Outcomes With Margetuximab and Pembrolizumab in Pretreated HER2-Positive Gastric/Gastroesophageal Adenocarcinoma

被引：0

作者：

Catenacci, Daniel V. T. ^{[1
]}

Kang, Yoon-Koo ^{[2
]}

Uronis, Hope E. ^{[3
]}

Lee, Keun-Wook ^{[4
]}

Ng, Matthew C. H. ^{[5
]}

Enzinger, Peter C. ^{[6
]}

Park, Se Hoon ^{[7
]}

Gold, Philip J. ^{[8
]}

Lacy, Jill ^{[9
]}

Hochster, Howard S. ^{[9
,26
]}

Cheul, Sang ^{[10
]}

Kim, Yeul Hong ^{[11
]}

Marrone, Kristen A. ^{[12
]}

Kelly, Ronan J. ^{[13
]}

Juergens, Rosalyn A. ^{[14
]}

Kim, Jong Gwang ^{[15
]}

Alcindor, Thierry ^{[16
]}

Sym, Sun Jin ^{[17
]}

Song, Eun-Kee ^{[18
]}

Chee, Cheng Ean ^{[19
]}

Chao, Yee ^{[20
]}

Kim, Sunnie ^{[21
,27
]}

Oh, Do-Youn ^{[22
]}

Yen, Jennifer ^{[23
]}

Odegaard, Justin I. ^{[23
]}

Lagow, Errin ^{[23
]}

Li, Daner ^{[24
]}

Sun, Jichao ^{[24
]}

Kaminker, Patrick ^{[24
]}

Moore, Paul A. ^{[24
]}

Rosales, Minori Koshiji ^{[24
,28
]}

Park, Haeseong ^{[25
]}

机构：

[1] Univ Chicago, Med Ctr, Chicago, IL 60637 USA

[2] Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea

[3] Duke Univ, Med Ctr, Durham, NC USA

[4] Seoul Natl Univ, Bundang Hosp, Coll Med, Seongnam, South Korea

[5] DukeNUS Duke Univ, Natl Canc Ctr Singapore, Natl Univ Singapore, Sch Med, Singapore, Singapore

[6] Dana Farber Brigham Canc Ctr, Boston, MA USA

[7] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Seoul, South Korea

[8] Swedish Canc Inst, Seattle, WA USA

[9] Yale Sch Med, New Haven, CT USA

[10] Korea Univ, Guro Hosp, Seoul, South Korea

[11] Korea Univ, Anam Hosp, Seoul, South Korea

[12] Johns Hopkins Univ, Baltimore, MD USA

[13] Baylor Univ, Med Ctr, Dallas, TX USA

[14] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada

[15] Kyungpook Natl Univ, Chilgok Hosp, Daegu, South Korea

[16] McGill Univ, Hlth Ctr, Montreal, PQ, Canada

[17] Gachon Univ, Gil Med Ctr, Incheon, South Korea

[18] Jeonbuk Natl Univ, Med Sch, Jeonju, South Korea

[19] Natl Univ Canc Inst, Singapore, Singapore

[20] Taipei Vet Gen Hosp, Taipei, Taiwan

[21] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA

[22] Seoul Natl Univ, Seoul Natl Univ Hosp, Grad Sch, Canc Res Inst,Coll Med,Integrated Major Innovat M, Seoul, South Korea

[23] Guardant Hlth, Redwood City, CA USA

[24] MacroGenics, Rockville, MD USA

[25] Washington Univ, Sch Med, St Louis, MO USA

[26] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA

[27] Univ Colorado, Canc Ctr, Aurora, CO USA

[28] Sesen Bio, Cambridge, MA USA

来源：

ONCOLOGY-NEW YORK | 2023年 / 37卷 / 04期

关键词：

gastric/gastroesophageal adenocarcinoma; HER2; ctDNA; and margetuximab plus pembrolizumab;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE. To assess the ability of circulating tumor DNA (ctDNA)-based testing to identify patients with HER2 (encoded by ERBB2)-positive gastric/gastroesophageal adenocarcinoma (GEA) who progressed on or after trastuzumab-containing treatments were treated with combination therapy of anti-HER2 and anti-PD-1 agents. METHODS. ctDNA analysis was performed retrospectively using plasma samples collected at study entry from 86 patients participating in the phase 1/2 CP-MGAH22-05 study (NCT02689284). RESULTS. Objective response rate (ORR) was significantly higher in evaluable ERBB2 amplification-positive vs - negative patients based on ctDNA analysis at study entry (37% vs 6%, respectively; P =.00094). ORR was 23% across all patients who were evaluable for response. ERBB2 amplification was detected at study entry in 57% of patients (all HER2 positive at diagnosis), and detection was higher (88%) when HER2 status was determined by immunohistochemistry fewer than 6 months before study entry. ctDNA was detected in 98% (84/86) of patients tested at study entry. Codetected ERBB2-activating mutations were not associated with response. CONCLUSIONS. Current ERBB2 status may be more effective than archival status at predicting clinical benefit from margetuximab plus pembrolizumab therapy. ctDNA testing for ERBB2 status prior to treatment will spare patients from repeat tissue biopsies, which may be reserved for reflex testing when ctDNA is not detected.

引用

页码：175 / 184

页数：10