BACKGROUND-Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non-small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase.

Recent therapeutic advances in oncology have been driven by the identification of tumour genotype variations between patients, called interpatient heterogeneity, that predict the response of patients to targeted treatments. Subpopulations of cancer cells with unique genomes in the same patient may exist across different geographical regions of a tumour or evolve over time, called intratumour heterogeneity. Sequencing technologies can be used to characterize intratumour heterogeneity at diagnosis, monitor clonal dynamics during treatment and identify the emergence of clinical resistance during disease progression. Genetic interpatient and intratumour heterogeneity can pose challenges for the design of clinical trials that use these data.

UGT1A1 genotype and total bilirubin levels are strongly associated with severe neutropenia, and could be used to identify cancer patients predisposed to the severe toxicity of irinotecan. The hypothesis that the -3156G>A variant is a better predictor of UGT1A1 status than the previously reported TA indel requires further testing.

BACKGROUNDCancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient‐reported outcome measure has been validated to assess this distress.METHODSPatients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health‐related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT‐G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test‐retest reliability, internal consistency, and validity of the COST measure were assessed using standard‐scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses.RESULTSA total of 375 patients with advanced cancer were approached, 233 of whom (62.1%) agreed to participate. The COST measure demonstrated high internal consistency and test‐retest reliability. Factor analyses revealed a coherent, single, latent variable (financial toxicity). COST values were found to be correlated with income (correlation coefficient [r] = 0.28; P<.001), psychosocial distress (r = ‐0.26; P<.001), and HRQOL, as measured by the FACT‐G (r = 0.42; P<.001) and by the EORTC QOL instruments (r = 0.33; P<.001). Independent factors found to be associated with financial toxicity were race (P = .04), employment status (P<.001), income (P = .003), number of inpatient admissions (P = .01), and psychological distress (P = .003). Willingness to discuss costs was not found to be associated with the degree of financial distress (P = .49).CONCLUSIONSThe COST measure demonstrated reliability and validity in measuring financial toxicity. Its correlation with HRQOL indicates that financial toxicity is a clinically relevant patient‐centered outcome. Cancer 2017;123:476–484. © 2016 American Cancer Society.

Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.