Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma

Hyo Song Kim, Sung Moo Kim, Hyunki Kim, Kyoung Ho Pyo, Jong Mu Sun, Myung Ju Ahn, Keunchil Park, Bhumsuk Keam, Nak Jung Kwon, Hwan Jung Yun, Hoon Gu Kim, Ik Joo Chung, Jong Seok Lee, Kyung Hee Lee, Dae Joon Kim, Chang Geol Lee, Jin Hur, Hyunsoo Chung, Jun Chul Park, Sung Kwan ShinSang Kil Lee, Hye Ryun Kim, Yong Wha Moon, Yong Chan Lee, Joo Hang Kim, Soonmyung Paik, Byoung Chul Cho

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The purpose of this study was to investigate the clinical activity, safety and predictive biomarkers of dacomitinib, an irreversible pan-HER inhibitor, in patients with recurrent or metastatic esophageal squamous cell carcinoma (R/M-ESCC). Patients, whose diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, were treated with dacomitinib 45mg/day. The primary endpoint was objective response rate by RECISTv 1.1. Predictive biomarker analyses included the characterization of somatic mutations and gene expression using the Ion Torrent AmpliSeq Cancer Hotspot Panel and Nanostring nCounter, and investigation of their relationship with clinical outcomes. Of the 48 evaluable patients, 6 (12.5%) achieved partial responses and 29 (60.4%) had stable disease. The median response duration was 7.1 months. The median progression free survival (PFS) and overall survival (OS) was 3.3 months (95% CI, 2.4-4.3 months) and 6.4 months (95% CI, 4.4-8.4 months). Adverse events were mostly grade 1-2. Gene set enrichment analysis revealed that ERBB signaling pathway is significantly enriched in patients with PFS ≥4 months (n = 12) than PFS < 4 months (n = 21) (p < 0.001). Upregulation of ERBB signaling pathway was significantly associated with longer PFS (5.0 vs. 2.9 months, P = 0.016) and OS (10.0 vs. 4.8 months, P = 0.022). The most frequent mutations were TP53 (61%) followed by CDKN2A (8%), MLH1 (8%), FLT3 (8%) and EGFR (8%). Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-ESCC. Screening of ERBB pathway-related gene expression profiles may help identify patients who are most likely benefit from dacomitinib.

Original languageEnglish
Pages (from-to)44971-44984
Number of pages14
JournalOncotarget
Volume6
Issue number42
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

Fingerprint Dive into the research topics of 'Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma'. Together they form a unique fingerprint.

  • Cite this

    Kim, H. S., Kim, S. M., Kim, H., Pyo, K. H., Sun, J. M., Ahn, M. J., Park, K., Keam, B., Kwon, N. J., Yun, H. J., Kim, H. G., Chung, I. J., Lee, J. S., Lee, K. H., Kim, D. J., Lee, C. G., Hur, J., Chung, H., Park, J. C., ... Cho, B. C. (2015). Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma. Oncotarget, 6(42), 44971-44984. https://doi.org/10.18632/oncotarget.6056