Appropriate use of tumour biomarkers for treatment with innovative drugs: A retrospective study

Abstract

Abstract. Performing randomised clinical trials to address the clinical usefulness of predictive and prognostic tumour markers is a complex process for several reasons, and observational experiences may thus play an important role. The present study performed an observational retrospective analysis in Area Vasta Romagna, Italy, collecting information on tumour marker determination in 760 consecutive patients who started a new line of anticancer therapy between January and June 2010. The determination of well-known biomarkers was requested for all gastrointestinal stromal tumour (GIST) patients (n=13) and for almost all breast cancer patients (n=369), and targeted therapies were consequently prescribed. Conversely, Kirsten rat sarcoma viral oncogene homolog (KRAS) determination in colon cancer patients (n=177) was requested in ~50% of advanced cases, while epidermal growth factor receptor (EGFR) determination was required in slightly more than 30% of the same patients. EGFR and KRAS determinations were requested in only 15% and 7.5% of non-small cell lung cancer (NSCLC) patients (n=201), respectively. There would appear to be greater appropriateness of tumour marker determination for breast cancer and GISTs than for colon cancer and NSCLC. Resources can be further optimised by standardising tumour marker determinations in terms of the timing of requests and the consequent use of the results for tailored treatment planning. IntroductionIn the age of personalised oncological patient care, clinical management decisions for these patients are increasingly being guided by predictive and prognostic tumour markers. As the number of available markers increases, resulting in significant use of healthcare financial resources, there is a pressing requirement for critical reviews of the body of evidence that confirms the clinical utility of these markers. Examples of these markers are oestrogen receptor and human epidermal growth factor receptor 2 (HER-2) status in breast cancer, which predict the benefit or resistance to endocrine and anti-HER-2 therapies, respectively. More recent investigations have shown that the presence of anaplastic lymphoma receptor tyrosine kinase translocations in lung cancer and the absence of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer can predict the benefit of crizotinib and anti-epidermal growth factor receptor antibodies, respectively. Considering the critical importance of prognostic and predictive tumour markers in making clinical decisions, they should be subject to the same evidence-based standards of medicine, including cost/utility analyses, as other medical interventions and practices (1).As highlighted by Henry and Hayes (2), three steps are necessary for developing a cancer biomarker: analytic validity, clinical validity and clinical utility. Demonstrating clinical utility, which is the assessment of the effectiveness of the biomarker, in addition to its benefit-to-harm ratio, appears to be the most crucial point. In fact, clinical utility has bee...