A randomized phase 2 study of temsirolimus and cetuximab versus temsirolimus alone in recurrent/metastatic, cetuximab‐resistant head and neck cancer: The MAESTRO study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155947/1/cncr32929_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155947/2/cncr32929.pd

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154935/1/cncr32762.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154935/2/cncr32762_am.pd

Evaluation of a novel rash scale and a serum proteomic predictor in a randomized phase II trial of sequential or concurrent cetuximab and pemetrexed in previously treated non-small cell lung cancer

BACKGROUND: Candidate predictive biomarkers for epidermal growth factor receptor inhibitors (EGFRi), skin rash and serum proteomic assays, require further qualification to improve EGFRi therapy in non-small cell lung cancer (NSCLC). In a phase II trial that was closed to accrual because of changes in clinical practice we examined the relationships among candidate biomarkers, quantitative changes in tumor size, progression-free and overall survival. METHODS: 55 patients with progressive NSCLC after platinum therapy were randomized to receive (Arm A) cetuximab, followed by pemetrexed at progression, or (Arm B) concurrent cetuximab and pemetrexed. All received cetuximab monotherapy for the first 14 days. Pre-treatment serum and weekly rash assessments by standard and EGFRi-induced rash (EIR) scales were collected. RESULTS: 43 patients (20-Arm A, 23-Arm B) completed the 14-day run-in. Median survival was 9.1 months. Arm B had better median overall (Arm B = 10.3 [95% CI 7.5, 16.8]; Arm A = 3.5 [2.8, 11.7] months P = 0.046) and progression-free survival (Arm B = 2.3 [1.6, 3.1]; Arm A = 1.6 [0.9, 1.9] months P = 0.11). The EIR scale distributed ratings among 6 rather than 3 categories but ordinal scale rash severity did not predict outcomes. The serum proteomic classifier and absence of rash after 21 days of cetuximab did. CONCLUSIONS: Absence of rash after 21 days of cetuximab therapy and the serum proteomic classifier, but not ordinal rash severity, were associated with NSCLC outcomes. Although in a small study, these observations were consistent with results from larger retrospective analyses. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT0020393

Versatile tests for comparing survival curves based on weighted log-rank statistics

The log-rank test is perhaps the most commonly used nonparametric method for comparing two survival curves and yields maximum power under proportional hazards alternatives. While the assumption of proportional hazards is often reasonable, it need not hold. Several authors have therefore developed versatile tests using combinations of weighted log-rank statistics that are more sensitive to nonproportional hazards. Fleming and Harrington (1991, Counting Processes and Survival Analysis, Wiley) consider the family of Gρ statistics and their supremum versions, while Lee (1996, Biometrics 52: 721–725) and Lee (2007, Computational Statistics and Data Analysis 51: 6557–6564) propose tests based on the more extended Gρ,γ family. In this article, I consider Zm = max(| Z1|, |Z2|, |Z3|), where Z1, Z2, and Z3 are z statistics obtained from G0,0, G1,0, and G0,1 tests, respectively. G0,0 corresponds to the log-rank test, while G1,0 and G0,1 are more sensitive to early and late-difference alternatives. I conduct a simulation study to compare the performance of Zm with the log-rank test, the more optimally weighted test, and Lee’s (2007) tests, under the null hypothesis, proportional hazards, early difference, and late-difference alternatives. Results indicate that the method based on Zm maintains the type I error rate, provides increased power relative to the log-rank test under early difference and late-difference alternatives, and entails only a small to moderate power loss compared with the more optimally chosen test. I apply the procedure to two datasets reported in the literature, both of which exhibit nonproportional hazards. Versatile tests such as Zm may be useful in clinical trial settings where there is concern that the treatment effect may not conform to the proportional hazards assumption. I also describe the syntax for a Stata command, verswlr, to implement the method

Predictors of emergency medical services utilization by elders.

OBJECTIVE: Elders (age \u3e or = 65 years) frequently use emergency medical services (EMS) for care. Understanding reasons for EMS use by elders may allow better management of EMS demand. To the best of the authors\u27 knowledge, no studies have identified patient characteristics associated with EMS use by elders. This study aimed to identify patient attributes associated with elder EMS users. METHODS: This was a prospective cohort study of non-institutionalized elders presenting to an urban university hospital emergency department. Nine hundred thirty elder patients completed the survey. The authors asked patients about access to care, health beliefs, and reasons for requesting EMS assistance. Univariate and logistic regression were used to identify predictors of EMS use. RESULTS: The sample had a mean age of 76 years; 37% were male; 79% were African American. Thirty percent arrived via EMS. Sixty-five percent of those transported and 46% of those not transported by EMS were admitted to the hospital (p \u3c 0.001). Reported reasons for using EMS transport included immobility (33%), illness (22%), request by others (21%), instruction from health care providers (10%), and lack of transportation (10%). Logistic regression identified symptom onset within four hours of seeking care (OR = 3.1), age \u3e or = 85 years (OR = 1.63), increased deficiencies in activities of daily living (OR = 1.40 per deficiency), worse physical functioning (OR = 1.14/10 points), and worse social functioning (OR = 1.06/10 points) as factors associated with EMS use. CONCLUSIONS: Elders report using EMS because of immobility, perceived medical needs, or requests by others. Similarly, the presence of acute illness symptoms, older age, and poor social and physical function, rather than health beliefs, predict EMS use among elders. These factors must be considered when managing the demand for EMS services