Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered

Muslim Diaspora in the West and International HRM

Interest in Islam and how Muslims organise themselves within the so-called Western world has largely stemmed from the flow of Muslim immigration since the 1960s and the 1970s (Loobuyck, Debeer, & Meier, 2013). Many of these immigrants have come to these new lands in the hope of making a better life for themselves economically, or to escape the political or religious pressures of their homeland (Lebl, 2014). Initially, deeming the influx of these foreigners to be largely irrelevant, there was little interest in their presence by the different governments across many jurisdictions. Typically, scant interest was shown towards entering into dialogue with the Muslim immigrant community. Indeed, until the 1990s, it was not uncommon for Islam to be perceived as a strange, foreign religion that was best managed through outsourcing to respective consulates (Loobuyck et al., 2013). Yet, migration and work-based mobility has a significant influence on the world of work and societies in which organisations are embedded. Many individuals migrate for better employment perspectives, as well as due to chain migration, betterment in the quality of life and based on fleeing famine, war and terror zones globally (Sharma & Reimer-Kirkham, 2015; Valiūnienė, 2016). Migration could involve upward as well as downward mobility/ wages, depending on the country and organisation. For example, minimum wages differ from € 184 in Bulgaria up to € 1923 in Luxembourg (Valiūnienė, 2016). Migration also contributes to the lived religion of diasporic communities as they navigate their faith at work (Sharma & Reimer-Kirkha

An evolutionary stage model of outsourcing and competence destruction : a Triad comparison of the consumer electronics industry

Outsourcing has gained much prominence in managerial practice and academic discussions in the last two decades or so. Yet, we still do not understand the full implications of outsourcing strategy for corporate performance. Traditionally outsourcing across borders is explained as a cost-cutting exercise, but more recently the core competency argument states that outsourcing also leads to an increased focus, thereby improving effectiveness. However, no general explanation has so far been provided for how outsourcing could lead to deterioration in a firm‟s competence base. We longitudinally analyze three cases of major consumer electronics manufacturers, Emerson Radio from the U.S., Japan‟s Sony and Philips from the Netherlands to understand the dynamic process related to their sourcing strategies. We develop an evolutionary stage model that relates outsourcing to competence development inside the firm and shows that a vicious cycle may emerge. Thus it is appropriate to look not only at how outsourcing is influenced by an organization‟s current set of competences, but also how it alters that set over time. The four stages of the model are offshore sourcing, phasing out, increasing dependence on foreign suppliers, and finally industry exit or outsourcing reduction. The evolutionary stage model helps managers understand for which activities and under which conditions outsourcing across borders is not a viable option. Results suggest that each of these firms had faced a loss of manufacturing competitiveness in its home country, to which it responded by offshoring and then outsourcing production. When a loss of competences occurred, some outsourcing decisions were reversed

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Contracting for Innovation: The difference in a case with fast-changing industrial background in China

Conventional contracting nowadays has disadvantages for fast-changing high-tech industries due to technology and market uncertainty. Observations found that cooperation between firms often operates in more innovative ways which were defined by Gilson et al. (2009) as ‘Contracting for Innovation’. However, their study was conducted in a developed market (i.e. the US) and thus the findings can hardly be used to explain what is observed in emerging markets which have significantly different industrial and market backgrounds. Using qualitative interviews from a case study, this paper aims to investigate contracting for innovation practices in a Chinese strategic alliance. Our findings suggest new functions compared to those in Gilson et al. (2009). This research has enriched ‘Contracting for Innovation’ theory against the background of emerging market with highly uncertain industrial environments

Towards a strategic understanding of global teams and their HR implications : an expert dialogue

Drawing on initial insights emerging from a panel at the EIBA 2016 Conference in Vienna, here discussants and expert panelists engage in a follow-on conversation on the HRM implications of global teams for international organizations. First we set out how HRM can enable global teams and their constituent members to overcome the new and considerable challenges of global teams. These challenges span levels of analysis, time and space. Next we debate global teams as a strategic response to the dual pressures of global integration and local adaptation. We consider what HRM is needed for global teams to successfully resolve this dilemma, challenging practitioners to move beyond the ‘best practices’ and ‘alignment’ dichotomy. Lastly we look to the future to consider implications for research. We propose a rich research agenda focused on the complexities of the global team context

How management control systems can facilitate a firm's strategic renewal and creation of financial intelligence

This chapter presents how management control systems and financial intelligence can facilitate a firm’s strategic renewal. Although the strategic accounting literature has recognized the importance of financial intelligence to a firm’s strategic decision making and formulation of strategy, the question of how a management control system (MCS) can help a firm to revamp and reallocate its resources has been overlooked in the prior strategy literature. In response, this chapter presents a conceptual model, which presents how advanced management accounting systems can foster a firm’s strategic renewal in light of the available theoretical foundations (the strategy implementation view, the dynamic capability perspective, and management accounting). This chapter advances managers’ understanding of firm’s renewal practices through the use of an MCS. Practical examples have been used to illustrate how firms renew their business operations in practice.fi=vertaisarvioitu|en=peerReviewed

Constructing global firms? National, transnational and neocolonial effects in international management consultancies

Drawing on an empirical study of four major international management consultancies, this article examines managerial efforts to construct ‘global’ organizations. We show how these efforts are undermined by inter-office conflicts over the staffing of client projects. We argue that such constraints cannot be adequately understood as an outcome of inappropriate organizational structures and incentives since this explanation ignores the important role of institutional contexts. In this vein, we outline and develop four different institutionalist lenses and apply them to the empirical findings. In so doing, we reveal the need to adopt a multi-dimensional institutionalist approach to the study of ‘global’ firms, one that can account for not only national effects but also transnational and neocolonial influences on these organizations

Determining how internal and external process connectivity affect supply chain agility: a life-cycle theory perspective

This paper examines how organizations connect internal and external processes to enable an agile response to continuous change. Drawing on life cycle theory, a hypothetical model is developed regarding the independent and combinative effects of internal and external process connectivity on supply chain agility and the moderating effect of product and supply complexity. The model is tested using hierarchical regression analysis based on survey data from 143 managers at German manufacturing firms. Our findings suggest that internal and external process connectivity have a positive effect on supply chain agility independently and collectively, with complexity having a moderating effect in particular instances. The findings build on prior research regarding the process-related enablers of supply chain agility; research that has yet to clearly differentiate between internal and external processes or uses the terms interchangeably. The theoretical contribution of the paper rests on its extension of life cycle theory to the supply chain