Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional cohort study.

BACKGROUND: The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC). METHODS: mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2-3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups. RESULTS: We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28-55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23-5.51), 1.51 (1.01-2.27), and 1.04 (0.76-1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01). CONCLUSION: Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.

Pharmacist involvement in the inhaler choice improves lung function in patients with COPD: a prospective single-arm study.

BACKGROUND: Currently, in Japan, shifting tasks from physician to hospital pharmacist is being developed to reduce physician workload and improve the quality of pharmacotherapy. This study aimed to investigate the effects of pharmacist involvement in the choice of inhaler as the task on the clinical outcomes of patients with chronic obstructive pulmonary disease (COPD). METHODS: This prospective, single-center, single-arm study included 36 outpatients with newly diagnosed COPD indicating inhaler therapy. Eligible patients were immediately interviewed by pharmacist. Then, pharmacist assessed patient's inhalation flow rate, physical function to handle an inhaler, comprehension, and value, and finally recommended a personalized inhaler based on originally developed inhaler choice protocol, and pulmonologist prescribed a pharmacist-selected inhaler. The primary endpoint was the improvement in trough forced expiratory volume in 1 s (FEV1) between baseline and week 26. The secondary endpoints were safety, and improvements at week 26 in scores for the COPD Assessment Test (CAT), modified British Medical Research Council Dyspnea Scale (mMRC), and Adherence Starts with Knowledge-20 (ASK-20). RESULTS: The pneumonologists completely agreed with the pharmacist-recommended inhaler. Mean FEV1 significantly increased from baseline to week 26 (1.60, SD 0.54 L vs. 1.98, SD 0.56 L; p < 0.0001). Significant improvements in CAT, mMRC, and ASK-20 scores were also observed. The prevalence of CAT responders as a negative predictor of acute exacerbation, defined as those with a decrease in CAT score of ≥2 points from baseline, was 86%. None of the patients experienced exacerbation during the study period. CONCLUSIONS: Pharmacist involvement in the choice of inhaler for patients with newly diagnosed COPD was associated with improved lung function, health status, clinical symptoms, and adherence to inhaler therapy. Shifting task of choosing appropriate inhaler from physician to hospital pharmacist may be performed effectively and safely with an inhaler choice protocol. TRIAL REGISTRATION NUMBER: UMIN000039722 , retrospectively registered on March 10, 2020.