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Published on: June 26, 2019
Lung Adenocarcinoma Developing Pleomorphic Carcinoma With ERBB3 Amplification After Acquired Resistance to Sotorasib:
Satoru Senoo1, Kohei Takata1, Shunsuke Matsumori1
1Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center, Hiroshima, Japan.
Introduction:
KRAS G12C inhibitors such as sotorasib have improved outcomes in KRAS G12C-positive nonsquamous NSCLC; however, the underlying mechanisms remain incompletely understood.
Case:
We report a 66-year-old man with advanced lung adenocarcinoma who received multiple lines of systemic therapy and subsequently responded to eighth-line sotorasib but later experienced disease progression. At progression, next-generation sequencing of a metastatic lesion revealed ERBB3 amplification without additional KRAS mutations. Postmortem examination revealed pleomorphic carcinoma.
Conclusion:
ERBB3 amplification may contribute to off-target resistance to sotorasib, and transformation to pleomorphic carcinoma may represent an additional resistance mechanism.
