raltegravir   the response was to some extent achieved by the combination of afatinib with paclitaxel. A limited number of studies in NSCLC have attempted to evaluate the activity of HER2-targeting agents, and have been summarized by Kelly et al. These studies could not reveal a significant benefit from trastuzumab or lapatinib. However, these studies were performed in NSCLC patient populations unselected for HER2 status (HER2 copy number or mutation) and primarily in combination with chemotherapeutic agents, and therefore

CP-690550 JAK inhibitor  were not apt to detect clinical benefit in patients with a genomic activation of HER2. There was, however, a report of one patient with a HER2 FISH positive tumor, but no HER2 or EGFR mutation, who achieved a short-lived response (4 weeks) to a pan-HER inhibitor (dacomitinib; PF-00299804) and subsequently progressed following additional treatment with trastuzumab, but who responded after vinorelbine was added. Furthermore, an additional patient with a HER2 mutation responded to trastuzumab plus vinorelbine after failure of platinum-based chemotherapy and gefitinib. However, this case does not allow for the assessment of the independent activity of trastuzumab This report suggests that the presence of HER2 mutations may characterize a subgroup of NSCLC that is buy CP-690550 

constitutively dependent on the HER2 pathway. Afatinib is a potential novel treatment option for this subgroup of patients, even when other EGFR and HER2 targeting purchase CP-690550 treatments have failed. The rate and duration of response associated with afatinib and the combined activity of afatinib and paclitaxel should be further assessed in earlier lines of treatment in this genomically defined population. This work was supported by Boehringer Ingelheim and grants from the National Cancer Plan, Action 29 (grant PNC/KNP-29-011), Belgium; and the Stichting tegen Kanker, Belgium