masitinib  Two other patients with HER2 mutations were enrolled into the study, but both cases were considered to be non-evaluable. One patient was a 51-year-old woman with a 4 pack-year smoking history (who stopped smoking 29 years before study entry). She was treated with afatinib monotherapy for 7 weeks and discontinued treatment due to the occurrence of Grade 3 rash. Stable disease was observed at this time. The patient received subsequent pemetrexed therapy with disease progression after two cycles,

 Chemical Libraries  followed by docetaxel with disease stabilization for 5 months, after which the patient was lost to follow-up. The second patient was a 62-year-old female, never smoker, who received afatinib for only 2 weeks and was discontinued due to Grade 3 diarrhea and deterioration of her general condition. No tumor assessments were undertaken within the study after baseline. The patient was subsequently lost to follow-up. We describe the first evidence of clinical benefit from treatment with afatinib in patients with an exon 20 HER2-mutant lung adenocarcinoma who have previously failed various chemotherapy regimens and the EGFR and/or HER2 inhibitors erlotinib, trastuzumab and lapatinib. Five patients were identified with a HER2 mutation, although only three were evaluable for response; mutations in all three patients were in exon 20 (two insertional duplications and one single amino-acid mutation). Analogous mutations in EGFR in exon 20 are relatively

 High Throughput Screening   insensitive to inhibition by the reversible inhibitor gefitinib 15. In two patients, a rapid metabolic response was observed within 1–2 weeks. Two patients had genomic activation of both EGFR and HER2. The most striking response to single-agent afatinib was observed in Case 1, with a p.Tyr772 Ala775dup mutation in HER2. Compared with the other two patients, this patient showed genomic activation of Screening Libraries HER2 only. This mutation causes an amino acid change identical to a mutation studied in a recently published preclinical model of mutant HER2-driven lung cancer 16.