MD Conference Express - ELCC 2015 - (Page 3)

Figure 2. Master Protocol for Lung-MAP Study of Squamous Cell Lung Cancer S1400: Master lung 1: squamous cell lung cancer-second-line therapy CT Biomarker nonmatch Biomarker proﬁling (NGS/CLIA) Nonmatch drug Multiple phase II-III substudies with rolling opening and closure Biomarker A TT A Biomarker B CT Primary end point PFS/OS TT B Biomarker C CT TT C +CT Primary end point PFS/OS Biomarker D CT Primary end point PFS/OS TT D+E E Primary end point PFS/OS CLIA, Clinical Laboratory Improvement Amendments; CT, chemotherapy (docetaxel or gemcitabine); E, erlotinib; NGS, next-generation sequencing; OS, overall survival; PFS, progression-free survival; TT, targeted therapy. Reproduced with permission from DR Gandara, MD. driver was identified in 44% of samples. Overall survival was improved substantially with a driver with bioguided treatment (HR, 0.5; 95% CI, 0.3 to 0.9; P = .014) compared with a driver without bioguided treatment or no driver identified. Patients with an ECOG PS of ≥ 2 were less likely to receive the driver with bioguided treatment; the incidence of brain metastases was similar in the 3 treatment groups. Prof Barlesi noted that a recent study in metastatic lung ADC conducted in the United States identified oncogenic drivers in 64% of patients and also found that matching therapy to the driver improved survival [Kris MG et al. JAMA. 2014]. In France, from 2015, there will be routine testing for molecular targets and matching of the treatment to the target, stated Prof Barlesi, and from 2017 there will be wider implementation of NGS. The results of the Biomarkers France study, including its ancillary studies in patients with specific mutations, may lead to a second such study. POTENTIAL MOLECULAR TARGETS FOR SQUAMOUS CELL CANCER OF THE LUNG Few molecular targets have been identified for squamous cell cancer of the lung. The NFE2L2 mutation is very frequent in squamous cell cancer of the lung, but there is no drug available to target it, according to Roman K. Thomas, MD, University of Cologne, Cologne, Germany. Although DDR2 mutations appear to be difficult to target, it is worthwhile to screen for the S768R mutation because of 2 case reports of a response to dasatinib [Pitini V et al. Lung Cancer. 2013; Hammerman PS et al. Cancer Discov. 2011]. FGFR1 mutations are a potential target in small cell lung cancer, and FGFR1 amplification is seen in about 22% of cases [Weiss J et al. Sci Transl Med. 2010]. The finding that FGFR1 amplification was sensitive to inhibition with PD173074 [Malchers F et al. Cancer Discov. 2014] led to a phase 1 study conducted by Prof Thomas and colleagues through Network Genomic Medicine in Germany, which provided central testing and outreach to nonacademic hospitals and oncologists and pulmonologists in private practice. Survival data were obtained through the national census. The study enrolled 4835 patients and successfully tested 3858 patients (79%). This is one of the largest single-center trials in the world in this patient population and includes about 80% of the lung cancer patients in the region and about 10% of those in Germany. The novel compound BGJ398, a highly selective FGFR1 inhibitor given as second- or third-line treatment, elicited a response in 16% of patients [Sequist LV et al. AACR 2014 (abstr CT326)]. This supports the notion that FGFR1 amplification is a treatable target in small cell lung cancer, stated Prof Thomas, and the responses were somewhat durable. The patient population who will benefit must be better discriminated. Peer-Reviewed Highlights From the European Society for Medical Oncology 2015 European Lung Cancer Conference 3

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MD Conference Express - ELCC 2015