Clinical response to a lapatinib-based therapy for a Li-Fraumeni syndrome patient with a novel HER2V659E mutation.
Genomic characterization of recurrent breast and lung tumors developed over the course of 10 years in a 29-year-old patient with a germline TP53 mutation (Li-Fraumeni Syndrome) identified oncogenic alterations in the HER2 and EGFR genes across all tumors, including HER2 amplifications, an EGFR-exon 20 insertion, and the first-in-humans HER2V659E mutation showing a phenotypic convergent evolution toward HER2 and EGFR alterations. Following the identification of HER2-activating events in the most recent lung carcinoma and in circulating tumor cells, we treated the reminiscent metastatic lesions with a lapatinib-based therapy. A symptomatic and radiologic clinical response was achieved. HER2V659E sensitivity to lapatinib was confirmed in the laboratory.


CONCLUSIONS
The precise knowledge of the genomic alterations present in tumors is critical to selecting the optimal treatment for each patient. Here, we report the molecular characterization and clinical response to a lapatinib-based therapy for the tumors of a Li-Fraumeni patient showing prevalence of HER2 and EGFR genomic alterations.
1Vall d'Hebron Institut d'Oncologia; 2Vall d'Hebron Institut de Recerca; 3Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona; 4Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain; and 5Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
Violeta
V
Serra
Ana
A
Vivancos
Xose S
XS
Puente
Enriqueta
E
Felip
Daniel
D
Silberschmidt
Ginevra
G
Caratù
Josep-Lluís
JL
Parra
Leticia
L
De Mattos-Arruda
Judit
J
Grueso
Javier
J
Hernández-Losa
Joaquín
J
Arribas
Ludmila
L
Prudkin
Paolo
P
Nuciforo
Maurizio
M
Scaltriti
Joan
J
Seoane
José
J
Baselga
D000328:Adult; D059472:Exome; D005260:Female; D006801:Humans; D000077341:Lapatinib; D016864:Li-Fraumeni Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human