Successful treatment of a patient with Li-Fraumeni syndrome and metastatic lung adenocarcinoma harboring synchronous EGFR L858R and ERBB2 extracellular domain S310F mutations with the pan-HER inhibitor afatinib.
We report the case of a young, never-smoker woman with Li-Fraumeni syndrome and advanced lung adenocarcinoma refractory to multiple lines of conventional chemotherapy and negative for actionable alterations by routine testing. Comprehensive genomic profiling by clinical-grade next generation sequencing was performed on 3320 exons of 184 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer. The tumor was found to harbor both EGFR L858R and ERBB2 S310F alterations and also tested positive for a known TP53 germline mutation. The presence of the EGFR mutation was further validated by direct sequencing. Based on these results, a dual EGFR/ERBB2 inhibitor, afatinib, was chosen for treatment. The patient achieved a rapid, complete, and durable response to afatinib monotherapy, both clinically and radiographically. The treatment was very well tolerated. This unique case raises practical questions as to the challenges of molecular testing and highlights the potential association of p53 mutations with concurrent EGFR and ERBB2 aberrations. As this case powerfully illustrates, the combination of broad genomic profiling and targeted therapy guided by mutational analysis offers the possibility of precision management of refractory advanced adenocarcinoma in the background of neoplastic syndromes.
New York Presbyterian Hospital-Columbia University Medical Center; New York, NY USA.
Yuxia
Y
Jia
Foundation Medicine, Inc.; Cambridge, MA USA.
Siraj M
SM
Ali
New York Presbyterian Hospital-Columbia University Medical Center; New York, NY USA.
Shumaila
S
Saad
New York Presbyterian Hospital-Columbia University Medical Center; New York, NY USA.
Courtney A
CA
Chan
Foundation Medicine, Inc.; Cambridge, MA USA.
Vincent A
VA
Miller
New York Presbyterian Hospital-Columbia University Medical Center; New York, NY USA.
Balazs
B
Halmos
D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000077716:Afatinib; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000150:complications / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
D000077716:Afatinib; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
EGFR; ERBB2; Li–Fraumeni syndrome; afatinib; genomic profiling; lung cancer; next generation sequencing