Aims Protein kinase inhibitors (PKI) have revolutionized the prognosis of several types of cancer, justifying the acceleration of their clinical evaluation before they obtain marketing authorization. Pharmacovigilance signals of heart failure (HF) following exposure to PKIs have been detected in recent years. Our objective was to identify the PKIs most frequently associated with the development of HF. Methods Using the French National Healthcare Database, all patients newly exposed to a PKI between January 2011 and June 2014 were followed up for 18 months. Specific hospitalisation diagnosis and long-term disease codes related to HF were used to identify HF patients. HF Incidence Rate Ratios (IRR) were measured and adjusted Hazard Ratios (aHR) were estimated using a Cox model. Results Thirteen PKIs were studied. Among the 49,714 new PKI users during the study period, the mean IRR of HF was 3.38 per 100 person-years, with a median time to onset of 155 days. We found a significant increase in the incidence of HF for 6 drugs: pazopanib (aHR= 2.42, 95% CI: 1.67-3.52), dasatinib (aHR= 2.22, 95% CI: 1.42-3.44), ruxolitinib (aHR= 2.11, 95% CI: 1.69-2.64), crizotinib (aHR= 1.71, 95% CI: 1.07-2.72), everolimus (aHR= 1.45, 95% CI: 1.26-1.67) and vemurafenib (aHR= 1.37, 95% CI: 1.01-1.86). Conclusions Our study provides knowledge on HF following exposure to a PKI. Additional studies could confirm these results for dasatinib, everolimus, pazopanib and ruxolitinib, and particularly for the two drugs with results slightly above the significance threshold, crizotinib and vemurafenib in our sensitivity analyses.

Aim: A better knowledge of opioid prescribing patterns would help to identify areas of potential improvement in cancer pain management. This study aimed to identify potential inappropriate use (PIU) of strong opioid analgesics in cancer outpatients in their last year of life. Methods: A retrospective cohort of cancer patients dead between 2011 and 2014 and who were exposed as outpatient to a strong opioid analgesic in the last year of life was identified in the “Echantillon Généraliste de Bénéficiaires” (a 1/97th random sample of the French general population). Prescribing patterns of strong opioids were analyzed and PIU was defined by at least one of these criteria: overlapping prescriptions; contraindicated prescriptions; lack of laxatives; potential drug interactions; prescription in patients hospitalized for opioid-related disorders. Factors associated with PIU were investigated through a multiple logistic regression model. Results: One third of the 2,236 patients (median age 72 years (IQR: 61-82), 44.1% of women) presented a PIU (insufficient laxative prescription (19.6% of patients), insufficient background treatment with transmucosal fentanyl (14.8%), overlapping prescriptions (2.6%)). The rate of PIU significantly decreased from 37.6% (2011) to 29.8% (2014). For patients with a duration of opioid use  3 months, factors associated with PIU were fentanyl prescription (aOR=2.36; 95% CI [1.86-3.00]) and previous use of strong opioid (aOR=1.88; [1.50-2.36]) Conclusion: In France, one third of cancer patients exposed to strong opioids experienced PIU and this proportion tended to decrease over time. There is still room for progress in cancer pain management at the end of life.