We retrospectively analyzed non-small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related. AEs labeled as possibly/probably related were considered trAEs for this analysis. The relationship between the incidence of a trAE and clinical outcomes was evaluated. Ninety-seven NSCLC patients treated on KEYNOTE-001 at the University of California, Los Angeles were evaluated. Ten percent (85/826) of AEs were trAEs, occurring in 40% (39/97) of patients. The most frequent trAEs were rash (21% patients), fatigue (6% patients), and hypothyroidism (6% patients). The 39 patients that experienced a trAE had increased objective response rate (ORR, 38.5%), progression-free survival (PFS: median, 248 days), and overall survival (OS: median, 493 days), compared with the 58 patients that did not (ORR: 8.9%, PFS: median 60 days, OS: median 144.5 days). The observed association between trAEs and improved clinical outcome persisted when using Cox proportional hazards regression models to assess the confounding effect of covariates and mitigate guarantee-time bias. The association also remained when data were substratified by grade, degree of association, and treatment-related select AE designation. This single-center analysis revealed that trAEs predicted for improved clinical outcome with pembrolizumab, and when controlling for guarantee-time bias and plausible confounders, this association remained. This observed relationship adds to our understanding of anti-PD-1 therapy and could aid clinicians in identifying patients most likely to benefit from therapy.

Background Clinical trials in lung cancer increasingly require subjects to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and subject selection have not been fully elucidated. Methods We retrospectively reviewed data generated by patients who consented to one or more interventional lung cancer clinical trials the UCLA Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. Results: 311 patients underwent 368 screening incidents for one or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs. 14 days) than trials that did not require a biopsy (p<0.001). Trials requiring a biopsy had a greater screen failure rate (49.1% v. 26.5%, p<0.001), largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. Conclusions: Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, it leads to a lengthening of the screening period, which, in some cases, is associated with clinical decline prior to enrollment. Implications for the interpretation of data from studies of this design should be explored.

Background and Aims: The lack of specificity has limited the role of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine whether AFP may decrease after achieving a sustained virological response (SVR) in patients with HCV-related cirrhosis. Methods: We performed a retrospective study of patients with HCV-related cirrhosis who were cured with direct-acting antiviral (DAA) therapy at the University of California, Los Angeles. Laboratory values, including serum AFP, were measured before and after completing the DAA treatment. Results: Fifty-six patients met the inclusion criteria, with median (interquartile range [IQR]) age of 67 (58-69) years and with 51.8% being male. All patients received DAA therapy without interferon. AFP decreased from median (IQR) 7.2 (4.2-13.4) ng/mL before DAAs to 4.2 (2.7-6.3) ng/mL at the end of treatment and 4.2 (2.9-6.8) ng/mL at 12 weeks after treatment (p < 0.001). Model for end-stage liver disease (MELD), fibrosis-4 (FIB4), and aspartate transaminase (AST) to platelet ratio index (APRI) scores at baseline were not significantly associated with AFP reduction. On multivariate analysis, platelet count, AST and total bilirubin at baseline were significantly correlated to AFP reduction (p = 0.04, 0.009 and 0.04, respectively). The higher the baseline AFP, the greater the reduction in AFP. There was no statistically significant correlation between baseline AFP and MELD, FIB4 or APRI scores. Conclusion: There was a significant decrease in AFP in patients with cirrhosis who achieved a SVR with DAAs. Given a reduction in AFP after DAA treatment, AFP should be further studied as a screening modality for HCC in patients with cirrhosis.

Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality and healthcare utilization in older adults. Diabetes mellitus is considered a risk factor for both frailty and falls in older adults. The aim of this study was to determine in a community cohort of older patients (65 years and older) with type 2 diabetes mellitus (T2DM) whether a history of falls is associated with frailty. Community dwelling older Veterans with T2DM underwent frailty assessment with the validated 5-item FRAIL Scale (frail ≥ 3; pre-frail 1-2; robust 0 points) between January 2016 and December 2017. We aggregated data on patients with a least one fall in the previous year. Binomial logistic regression was used to examine the association between a history of falls in the previous year and frailty. Among 868 patients (mean age 74 ± 7 years, 98% men), 31% were robust, 36% prefrail, and 33% frail. Over the previous year, 164 falls occurred among 1older patients. The number of older individuals with at least one fall in the previous year was significantly higher in the frail as compared with prefrail and robust groups: 20%, 9%, and 9% respectively (p&lt;.0005). A history of falls in the previous year was associated with an increased risk for frailty (odds ratio: 2.54 95% CI: 1.60-4.03). The population-attributable risk associated with a history of falls was 44% for frailty. In conclusion, a history of falls in the previous year is a strong predictor of frailty in older patients with T2DM. Falls should be a key component of the clinical evaluation of older patients with T2DM. Disclosure W. Valencia: None. N. Moghadam: None. J. Balda-Canizares: None. M.J. Mintzer: None. S. Dang: None. J.G. Ruiz: None.