Patterns of practice in oncology: is progress reaching our practice?

The last two decades have been characterised by significant progress in the understanding of the biology as well as the development of effective therapies for advanced cancer. Importantly, most of these therapies do not include traditional cytotoxic chemotherapy but agents which target specific pathways, proven, by basic science, to be important for the behaviour of the disease and, thus, their inhibition results in arrest of tumour growth (targeted therapies). These novel therapies have created enthusiasm among physicians and great anticipation among patients. Many of these modern agents have been endorsed by international guidelines and gained approval by FDA and EMEA due to the significant improvement of patients’ outcome, which they produced compared to older standards. It is, therefore, crucially important that these therapies are offered to all appropriate patients. Recent data from various malignancies indicate that there may be a diversion of everyday clinical practice from guidelines and evidence-based medicine (Fedeli et al. 2011; Boland et al. 2013; Bamias et al. 2015). Several factors could account for this: drug unavailability; lack of reimbursement by local and national authorities; physician inability to completely follow the most recent developments, especially when they work within environments which do not support a special focus in certain malignancies; and lack of acceptability of certain guidelines (for a variety of reasons). Regardless of the occasional justification of such diversion, the net result of such limitations could be the reduced availability of patients with potentially lethal diseases to the best available therapies. Consequently, mapping and auditing patterns of clinical practice across international boundaries provide snapshots of clinician behaviour, which may help illuminate the factors influencing prescribing decisions and thus patient outcomes. Melanoma is a malignant neoplasm of the skin. When it metastasises to lymph nodes or distant organs it carries a high risk of death form the disease (Lens & Dawes 2004). The context described above is particularly relevant for advanced melanoma. Although cytotoxic chemotherapy is largely ineffective, recent advances in our knowledge of cancer immunoediting have led to the development of several new agents, which stimulate an immune response against melanoma. These agents have shown unprecedented efficacy and rapidly gained approval for the treatment of this disease. In this issue of European Journal of Cancer Care, Jones et al. (2015a,b) present two important papers, which are complementary to each other: the first describes treatment patterns for advanced melanoma across Europe and the second addresses the unmet clinical needs which arise as the result of such practices. Although the studies by Jones et al. are reported only three years after the publication of a similar survey by Lebbe et al. (2012), they are highly relevant because two agents which produced significant prolongation of survival, ipilimumab and vemurafenib (Hodi et al. 2010; Chapman et al. 2011; Robert et al. 2011), have been licensed in Europe since then (August 2011 and February 2012, respectively). This shows the importance of repeating such studies in order to capture ongoing changes in practice. Although the two studies report different results, the methodology was similar: data were collected using questionnaires of 63 questions relating to the respondents’ clinical practice in the previous 12 months. The first study was conducted in several countries but only the results of the ‘big five’ European countries (EU 5), i.e. UK, Germany, France, Italy and Spain were reported in this paper. The second included a further three European countries (Belgium, the Netherlands and Sweden) and also Australia, Brazil, Canada and Mexico. Understandably, the second study was larger but both studies recruited a meaningful number of physicians (150 and 343). Importantly, an effort was made for balanced representation of countries and regions. Drug availability and reimbursement issues affected the prescription of vemurafenib in Spain and Italy, where the drug was not reimbursed at the time of the survey. On the contrary, several (and partially undetermined) factors dictated practices in second-line treatment. Although ipilimumab was licensed by the EMA for use after prior systemic therapy, temozolomide and fotemustine were more commonly used in Italy and Spain. The main finding of the second study was that toxicity and tolerability of the agents studied was reported as a top concern in all countries, which participated. Considerable numerical differences across countries were reported. Utilisation of ipilimumab and vemurafenib varied across countries with Brazil and Mexico showing the lowest rates. The two studies are important for several reasons. They demonstrate how clinicians operate at the cusp of a rapidly changing oncological therapeutic milieu. In this context the findings may, to a certain degree, be generalisable. The concerns of the physicians involved and the differences in the utilisation of two novel agents mirror the findings of studies in other neoplasms, as described above: lack of an established treatment algorithm, e.g. ‘the lack of validated treatment flow charts (sequence of drugs)’, ‘rapidly evolving new drugs but the sequencing of them makes it difficult’ (Italy, 13%; and Mexico, 17%); centralising care, ‘centralising treatment stage IV melanoma is important for good information, but means high costs for that centre’ (the Netherlands, 27%), were frequently reported in the second study. Furthermore, at the time of the collection of data, ipilimumab and vemurafenib were not reimbursed by public health systems in many countries. Reasons related to the particular malignancy were also highlighted: limited treatment options remain after the introduction of ipilimumab and vemurafenib; ‘the delays of BRAF testing’; ‘it is too complicated to do BRAF testing’ (Canada, 20%; and Spain, 17%). Clearly, all the above-mentioned reasons represent areas of potential improvement in our current practices. Furthermore, in spite of the undisputed efficacy of new agents, clinicians continue to have concerns about treatment options, which remind the readers that advanced cancer largely remains an incurable disease. The most serious limitation of these two studies is the lack of any survival data. Therefore, the effect of the limitations described in the second paper on the outcome of patients with advanced melanoma cannot be assessed. This does not undermine, however, the importance of accurately describing patterns of practice across countries because this is the first step in understanding the reasons behind our inability to fully take advantage of the developments in cancer therapy for the benefit of our patients.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.