Efficacy and safety of rociletinib versus chemotherapy in patients with EGFR-mutated NSCLC: the results of TIGER-3, a phase 3 randomized study

Introduction: The TIGER-3 (NCT02322281) study was initiated to compare the efficacy and safety of rociletinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets EGFR T790M and common EGFR-activating mutations, versus chemotherapy in patients with NSCLC who progressed on first- or second-generation EGFR TKIs. Methods: Patients with advanced or metastatic EGFR-mutated NSCLC with disease progression on standard therapy (previous EGFR TKI and platinum-based chemotherapy) were randomized to oral rociletinib (500 or 625 mg twice daily) or single-agent chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel). Results: Enrollment was halted when rociletinib development was discontinued in 2016. Of 149 enrolled patients, 75 were randomized to rociletinib (n = 53: 500 mg twice daily; n = 22: 625 mg twice daily) and 74 to chemotherapy. The median investigator-assessed progression-free survival (PFS) was 4.1 months (95% confidence interval [CI]: 2.6-5.4) in the rociletinib 500-mg group and 5.5 months (95% CI: 1.8-8.1) in the 625-mg group versus 2.5 months (95% CI: 1.4-2.9) in the chemotherapy group. An improved PFS was observed in patients with T790M-positive NSCLC treated with rociletinib (n = 25; 500 mg and 625 mg twice daily) versus chemotherapy (n = 20; 6.8 versus 2.7 mo; hazard ratio = 0.55, 95% CI: 0.28-1.07, p = 0.074). Grade 3 or higher hyperglycemia (24.0%), corrected QT prolongation (6.7%), diarrhea (2.7%), and vomiting (1.3%) were more frequent with rociletinib than chemotherapy (0%, 0%, 1.4%, and 0%, respectively). Conclusions: Rociletinib had a more favorable median PFS versus chemotherapy but had higher rates of hyperglycemia and corrected QT prolongation in patients with advanced EGFR-mutated NSCLC who progressed on previous EGFR TKI. Incomplete enrollment prevented evaluation of the primary efficacy end point

How do things become strategic? ‘Strategifying’ corporate social responsibility

How do things become ‘strategic’? Despite the development of strategy-as-practice studies and the recognized institutional importance of strategy as a social practice, little is known about how strategy boundaries change within organizations. This article focuses on this gap by conceptualizing ‘strategifying’ – or making something strategic – as a type of institutional work that builds on the institution of strategy to change the boundaries of what is regarded as strategy within organizations. We empirically investigate how corporate social responsibility has been turned into strategy at a UK electricity company, EnergyCorp. Our findings reveal the practices that constitute three types of strategifying work – cognitive coupling, relational coupling and material coupling – and show how, together and over time, these types of work changed the boundaries of strategy so that corporate social responsibility became included in EnergyCorp’s official strategy, became explicitly attended to by strategists and corporate executives and became inscribed within strategy devices. By disambiguating the notions of strategifying and strategizing, our study introduces new perspectives for analysing the institutional implications of the practice of strategy

Strategisches Handeln von Startups im Kontext der Mediatisierung

Junge Gründer und Start-ups müssen sich in einer schnell wandelnden und mediatisierten Wettbewerbsumwelt behaupten. Ihr Handeln wird geprägt von sozialen Netzwerkmedien wie Facebook, LinkedIn oder Instagram. Um auf diesen Medien-plattformen erfolgreich zu sein, müssen Markenführung und Markenkommunikation strategisch verankert sein. Der Aufsatz präsentiert daher eine qualitative Analyse empirischer Daten aus dem Kontext des Start-up-Incubator neudeli der Bauhaus-Universität Weimar und verdeutlicht, dass die Mediatisierung grundlegend in die strategische Entwicklung der Marke von jungen Gründern und Start-ups eingreift. Die Studie verdeutlicht das Verständnis strategischer Markenführung in mediatisierten Kontexten und zeigt, dass drei idealtypische Praktiken zur Markenführung und strategischen Entwicklung beitragen: 1) Bürokratische Medienarbeit, 2) Mediale Kreativarbeit, 3) Netzwerkarbeit durch Medien

Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With EGFR-Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study.

INTRODUCTION: The TIGER-3 (NCT02322281) study was initiated to compare the efficacy and safety of rociletinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets EGFR T790M and common EGFR-activating mutations, versus chemotherapy in patients with NSCLC who progressed on first- or second-generation EGFR TKIs. METHODS: Patients with advanced or metastatic EGFR-mutated NSCLC with disease progression on standard therapy (previous EGFR TKI and platinum-based chemotherapy) were randomized to oral rociletinib (500 or 625 mg twice daily) or single-agent chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel). RESULTS: Enrollment was halted when rociletinib development was discontinued in 2016. Of 149 enrolled patients, 75 were randomized to rociletinib (n = 53: 500 mg twice daily; n = 22: 625 mg twice daily) and 74 to chemotherapy. The median investigator-assessed progression-free survival (PFS) was 4.1 months (95% confidence interval [CI]: 2.6-5.4) in the rociletinib 500-mg group and 5.5 months (95% CI: 1.8-8.1) in the 625-mg group versus 2.5 months (95% CI: 1.4-2.9) in the chemotherapy group. An improved PFS was observed in patients with T790M-positive NSCLC treated with rociletinib (n = 25; 500 mg and 625 mg twice daily) versus chemotherapy (n = 20; 6.8 versus 2.7 mo; hazard ratio = 0.55, 95% CI: 0.28-1.07, p = 0.074). Grade 3 or higher hyperglycemia (24.0%), corrected QT prolongation (6.7%), diarrhea (2.7%), and vomiting (1.3%) were more frequent with rociletinib than chemotherapy (0%, 0%, 1.4%, and 0%, respectively). CONCLUSIONS: Rociletinib had a more favorable median PFS versus chemotherapy but had higher rates of hyperglycemia and corrected QT prolongation in patients with advanced EGFR-mutated NSCLC who progressed on previous EGFR TKI. Incomplete enrollment prevented evaluation of the primary efficacy end point