Optimizing the management of advanced non-small-cell lung cancer: a personal view

Mark D. Vincent

Abstract


The management of advanced nonsmall cell lung cancer is currently undergoing one of its rare paradigm shifts,  this time genuinely reflecting the most important meaning of the term: a change in the understanding of causal relationships.  Just as the nihilism of the 1970s gave way to the  empiricism of the 1980s and 1990s,  years of molecular research have this decade culminated in the first truly rational therapies based on informed design.  In addition, molecular markers and traditional parameters can now be combined to provide a framework of knowledge which will guide the application of  both the new, and also those older therapies which remain effective.   This framework, as important a component of the rational paradigm as the new drugs themselves, is necessary to decide who should and crucially, who should not receive the various components of this rapidly expanding armamentarium. The speed at which new knowledge now arrives, coupled with the persistent high level of unmet medical need, suggests that the traditional pace of evidence-based review needs to be accelerated.  Indeed, the increased scope for personalized management constitutes something of a challenge to ‘business-as-usual’ evidence-based medicine.  All of this will require substantial investment on the part of payers, which may or may not be possible. In the meantime, some patients may wish to, and may be financially able to take advantage of modern developments before they have been fully digested by the public payer system.  Responsive clinicians face difficult trade-offs as they try to balance the pros and cons of early adoption versus excessive conservatism.  Here is a personal view of how to navigate these waters, and although it is written especially for those patients who like to be the captain of their own ships, there is good reason to believe that all patients will eventually be managed by similar if not identical means.   Using the currently accepted guidelines as a springboard, I have highlighted areas where new knowledge is most likely to change practice and referenced the most authoritative sources for these views.  Generally, consideration has been given to large, recent, randomized trials of well known drugs, and the biomarker studies which have accompanied them. Some of these have been fully published but others have only been presented at major international meetings, but with results that are unlikely to change much. The most important developments include an increasing acceptance of maintenance therapy, and the consequent erosion of the concept of three distinct “lines of therapy”; a realization that kras and EGFR mutational status and, EGFR gene copy number by FISH, are ready for incorporation into clinical decision making, and that one of the implications of this is that not everyone should receive “all lines” of therapy; that histology is a reliable guide to differential drug selection throughout treatment; that pemetrexed, a novel cytotoxic, should now be incorporated into 1st and/or maintenance therapy of non-squamous patients; that bevacizumab appears to reliably increase objective response rates and progression-free survival,  and is thereby likely to improve symptom control; that prophylactic use of bisphosphonates, cranial irradiation and anticoagulation could substantially avoid certain disease complications in high risk patients; and that some of these events, and even toxicity, are largely predictable even without complex genomic analysis.

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DOI: http://dx.doi.org/10.3747/co.v16i4.465

Copyright © 2014 Multimed Inc.
ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)