MD Conference Express - ELCC 2015 - (Page 13)

TG4010 (n = 85) or placebo (n = 85) was conducted after 144 events of disease progression. In the patients with normal TrPAL levels, the primary end point of PFS was achieved in 70 patients (82.4%) receiving TG4010 and 74 patients (87.1%) receiving placebo. The observed hazard ratio (HR) for PFS was 0.74 (95% CI, 0.53 to 1.02), which corresponded to a 98.6% Bayesian probability that the true HR was < 1 and thus passed the necessary threshold of 95% to have met the efficacy end point in the normal TrPAL patient population. In patients with normal TrPAL levels, median PFS favored the TG4010 treatment arm compared with standard chemotherapy alone (5.7 vs 5.1 months, respectively; HR, 0.78; 95% CI, 0.53 to 1.02; P = .078). The overall response rate was 37.6% in the TG4010 treatment arm compared and 30.6% in the placebo arm of the patients with a normal TrPAL level. The analysis of patients with high TrPAL levels is still pending. Most grade 3/4 adverse events were similar between the treatment arms and included neutropenia, thrombocytopenia, fatigue, anemia, and febrile neutropenia with higher TG4010-related adverse events at the injection site (31.4% vs 4%). Subgroup analyses in patients with nonsquamous NSCLC (n = 195) showed a significant improvement in PFS when treated with TG4010 (HR, 0.71; 95% CI, 0.51 to 0.97; P = .016), with an increase in OS (HR, 0.73; 95% CI, 0.50 to 1.07). In the 75% of patients with the lowest baseline TrPAL levels (low TrPAL; n = 152), the HR for PFS was 0.66 (95% CI, 0.46 to 0.96; P = .014). In the patients with nonsquamous NSCLC and low TrPAL levels (n = 131), PFS was significantly increased in the TG4010 arm vs placebo (HR, 0.60; 95% CI, 0.41 to 0.88) and OS was increased with TG4010 vs placebo (HR, 0.70; 95% CI, 0.45 to 1.10). Forest plots of PFS and OS in the stratified subgroups are shown in Figures 1 and 2. Prof Quoix concluded that the results of the phase 2b portion of the TIME study provided evidence of the efficacy and safety of TG4010 in stage IV NSCLC, especially in patients with nonsquamous tumors and low TrPAL levels. LUX-Lung 5: Afatinib Plus Paclitaxel Improves Outcomes for Metastatic NSCLC Written by Anita Misra-Press, PhD Patients with advanced non-small cell lung cancer (NSCLC) who have wild-type EGFR fare better with conventional chemotherapy instead of tyrosine kinase inhibitors (TKIs) as first-line treatment [Lee JK et al. JAMA. 2014]. In contrast, 70% of patients with NSCLC harboring EGFR mutations show tumor regression from the EGFR TKIs erlotinib and gefitinib [Jackman D et al. J Clin Oncol. 2010]. The majority of these patients eventually acquire resistance to erlotinib and gefitinib, contributing to disease progression. Because of tumor cell heterogeneity, inclusion of an EGFR TKI in postprogression therapy improves outcomes. For instance, a combination of gefitinib or erlotinib plus pemetrexed has been shown to improve outcomes in 27 patients with EGFR mutation-positive NSCLC who had disease progression on gefitinib/erlotinib monotherapy; an overall response rate of 25.9% (95% CI, 62.1% to 95.5%) was achieved with the combination [Yoshimura N et al. J Thorac Oncol. 2013]. Afatinib, an irreversible ErbB TKI (including EGFR, HER2, HER4), increases survival outcomes as monotherapy and overcomes resistance in patients who had disease progression after gefitinib/erlotinib [Katakami N et al. J Clin Oncol. 2013; Sequist LV et al. J Clin Oncol. 2013]. Martin Schuler, MD, West German Cancer Center, Essen, Germany, shared results of LUX-Lung 5 [Schuler M et al. Ann Oncol. 2015], a randomized, open-label, 2-stage design, phase 3 trial that assessed continued afatinib plus paclitaxel vs investigator's choice of single-agent chemotherapy (ICC). The study consisted of 2 parts. In part A, patients with NSCLC who had failed ≥ 1 line of chemotherapy (including platinum/pemetrexed) and erlotinib/ gefitinib after ≥ 12 weeks of treatment (n = 1154) were treated with afatinib 50 mg/d. In part B, patients who had been treated with afatinib for ≥ 12 weeks followed by disease progression after part A of the study were eligible to be randomized 2:1 to afatinib 40 mg/d plus paclitaxel 80 mg/m2/wk or ICC. The primary end point was progression-free survival, whereas the secondary end points included overall survival, objective response rate, safety, and health-related quality-of-life outcomes. Of the 1154 patients who had disease progression on erlotinib/gefitinib and afatinib 50 mg/d, 202 patients derived ≥ 12 weeks of benefit on afatinib monotherapy. These selected patients were randomized 2:1 to receive afatinib plus paclitaxel (n = 134; 40 mg/d; 80 mg/m2/wk) or ICC (n = 68). Baseline patient characteristics (included sex, age, ECOG performance status, race, smoking status, clinical stage, and tumor histology) were well balanced between both arms. Progression-free survival increased from 2.8 months with ICC to 5.6 months with afatinib plus paclitaxel (HR, 0.60; 95% CI, 0.43 to 0.85; P = .0031). Afatinib plus paclitaxel, as fourth-line treatment, was also more effective than ICC in reducing tumor size (15.1% vs 1.2%). Although disease control rate (OR, 3.4; P < .0001) and objective response rate (OR, 3.1; P = .0049) were superior Peer-Reviewed Highlights From the European Society for Medical Oncology 2015 European Lung Cancer Conference 13

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MD Conference Express - ELCC 2015