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Purpose: Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB)., Methods: In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38)., Results: Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B., Conclusions: The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation., (© 2022. The Author(s).)

Introduction: Acute kidney injury is an expected adverse drug reaction listed in the European Union (EU) Summary of Product Characteristics (SmPC) for levetiracetam, one of the most widely used modern antiseizure medications (ASMs)., Objective: We conducted a voluntary post-authorization safety study to characterize the rate of acute renal failure (ARF) in patients exposed to levetiracetam versus other ASMs., Methods: New users of ASMs without prior renal dysfunction were identified and followed for 30 days in the IBM ® MarketScan ® database (USA, January 2008-December 2017). ARF was defined as a diagnosis on inpatient or emergency department claims. We estimated adjusted incidence rates, incidence rate ratios (IRRs), and incidence rate differences (IRDs) of ARF in patients initiating levetiracetam versus other ASMs., Results: Overall, 110,336 patients were eligible for the monotherapy cohort and 96,215 were eligible for the polytherapy cohort. The overall crude rate of ARF following a new ASM was 6.0 and 6.5 per 10,000 patients for the 'monotherapy' and 'polytherapy' cohorts, respectively, in the first 30 days after the index date. In the monotherapy cohort, the IRR for ARF was 1.37 (95% confidence interval [CI] 0.80-2.34) and the corresponding IRD was 2.0 (95% CI - 1.12 to 5.12) additional ARFs per 10,000 patient-months. In the polytherapy cohort, the adjusted IRR for ARF was 0.94 (95% CI 0.51-1.74) and the corresponding IRD was - 0.42 cases per 10,000 patient-months (95% CI - 4.01 to 3.17)., Conclusions: The rate of ARFs in ASM new users was very low. In patients without prior ASMs, the estimated difference in risk of ARF associated with initiation of levetiracetam versus initiation of other ASMs was small, with 95% CIs compatible with small protective or harmful effects. In patients receiving polytherapy, the difference was compatible with the null and the 95% CI with small protective or harmful effects., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To compare existing algorithms for classifying screening vs diagnostic colonoscopies and to quantify the increase in screening colonoscopy rates when Medicare began reimbursement in 2001 and when the Affordable Care Act (ACA) eliminated cost-sharing., Data Sources: Twenty percent random sample of fee-for-service (FFS) Medicare claims, 2000-2012., Study Design: Using recent administrative codes as tarnished gold standards, we examined the sensitivity and specificity of five published algorithms for classifying colonoscopies and calculated annual screening colonoscopy rates. We estimated the change in rates after Medicare began reimbursement and used difference-in-differences analysis to estimate the effects of eliminating cost-sharing by comparing states with and without a mandate to cover screening colonoscopy prior to the ACA., Findings: Model-based algorithms have higher sensitivity (0.53-0.99) than expert-based algorithms (0.35-0.39), but lower specificity (0.43-0.65 vs 0.79-0.88). All algorithms detected increases in screening from both Medicare's reimbursement change (range: 24-93/10 000) and the 2011 cost-sharing change (range: 1.1-34/10 000). Difference-in-difference estimates of the ACA's effect varied from 51 to 155 tests per 10 000 depending on the algorithm., Conclusions: Screening colonoscopy rates increased after eliminating cost-sharing in 2011, but the increase's size varied depending on the algorithm used to classify the indication. Improvements are needed in Medicare coding for screening., (© Health Research and Educational Trust.)