Randomized, Phase II Trial of Pemetrexed and Carboplatin with or without Enzastaurin versus Docetaxel and Carboplatin as First-Line Treatment of Patients with Stage IIIB/IV Non-small Cell Lung Cancer

Enzastaurin is an oral serine/threonine kinase inhibitor that targets protein kinase C-beta (PKC-β) and the phosphatidylinositol-3-kinase/AKT pathway. This trial assessed pemetrexed-carboplatin ± enzastaurin to docetaxel-carboplatin in advanced non-small cell lung cancer.Patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and performance status 0 or 1 were randomized to one of the three arms: (A) pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500 mg daily until disease progression, (B) the same regimen of pemetrexed-carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles. The primary end point was time to disease progression (TTP).Between March 2006 and May 2008, 218 patients were randomized. Median TTP was 4.6 months for pemetrexed-carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months for docetaxel-carboplatin (differences not significant). Median survival was 7.2 months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed-carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank = 0.05). Compared with the other arms, docetaxel-carboplatin was associated with lower rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4 febrile neutropenia.There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin

NUDGING QUALITY IMPROVEMENT IN CANCER CARE: INFLUENCE OF A CLINICAL DECISION SUPPORT SYSTEM TO NUDGE ADHERANCE TO EVIDENCE BASED GUIDELINES IN ADULT CANCERS

Cancer care is changing rapidly. Understanding of the increasing subtypes of cancer and exponentially increasing therapeutic interventions are unprecedented due to the rapid pace of scientific discovery and clinical innovation. This immense change within the field, lends itself to quality control initiatives, especially among general oncology providers who see a wide array of cancer types as general oncologists will see many different tumor types, and most of which have several potential treatment choices that have grown over time. Evidence-based pathways are an effective way to nudge quality control by presenting choice architecture at the point of care to facilitate guideline compliance among a wide array of therapeutic choices. This evaluated the impact of a clinical decision support system (CDSS) tool, a nudge within the electronic health record among a network of oncology providers. This study examined the results of its implementation across 9 statewide practices over 6-month interval. We evaluated the effects of the CDSS on regimen compliance with value pathways across practices, within practices, and the influence on physician compliance with value pathways across the study interval. SAS 9.4 software was used to evaluate the hypothesis using multi level modeling. Across the 29,926 regimens included in the study, the CDSS tool significantly impacted compliance to evidence based pathways. By applying a multi-level logistic regression model to the entire cohort, and segregating the levels as patients as level 1, doctors as level 2, and practices as level 3, the post CDSS implementation odds ratio of compliance to evidence based pathways was 1.48 (1.25;1.76). When we segmented the cohort by practices, the majority of individual practices had a significantly higher likelihood of evidence based pathways compliance after implementation of the CDSS tool with odds ratios of 1.60 (1.33;1.94), 1.13 (0.88; 1.45), 1.39 (1.08; 1.79), 1.85 (1.53; 2.24), 1.76 (1.32; 2.36), 1.71 (1.38; 2.11), 1.23 (0.96; 1.57), 1.37 (1.12; 1.67) and 1.46 (1.30; 1.63). In addition, each oncologist’s compliance was evaluated and, while we did not demonstrate a statistically significant improvement in compliance with the limited number of evidence based pathways prescribed by each oncologist with implementation of the tool, the number of regimens by oncologist was very low. Using McNemar’s test we did find that the percentage of oncologists who reached an individual benchmark of 75% compliance was significantly higher with implementation of the CDSS tool: among the 560 physicians included in this study, 327 (58%) were at or above a benchmark of 75% compliance prior to the CDSS tool and 402 (72%) achieved that benchmark after implementation of the CDSS tool (p\u3c0.001). In conclusion, implementation of the CDSS tool can be a successful mechanism to increase compliance to evidence-based pathways overall, and within most individual practices. In addition, physician compliance to benchmark performance of 75% compliance with evidence-based pathways can be improved by implementing a CDSS tool embedded within the EHR

Real-world survival outcomes of heavily pretreated patients with refractory HR+, HER2−metastatic breast cancer receiving single-agent chemotherapy—a comparison with MONARCH 1

Abemaciclib; Càncer de mama metastàsic; Supervivència globalAbemaciclib; Cáncer de mama metastásico; Supervivencia globalAbemaciclib; Metastatic breast cancer; Overall survivalPurpose In MONARCH 1 (NCT02102490), single-agent abemaciclib demonstrated promising efficacy activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2− metastatic breast cancer (MBC). To help interpret these results and put in clinical context, we compared overall survival (OS) and duration of therapy (DoT) between MONARCH 1 and a real-world single-agent chemotherapy cohort. Methods The real-world chemotherapy cohort was created from a Flatiron Health electronic health records-derived database based on key eligibility criteria from MONARCH 1. The chemotherapies included in the cohort were single-agent capecitabine, gemcitabine, eribulin, or vinorelbine. Results were adjusted for baseline demographics and clinical differences using Mahalanobis distance matching (primary analysis) and entropy balancing (sensitivity analysis). OS and DoT were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results A real-world single-agent chemotherapy cohort (n = 281) with eligibility criteria similar to the MONARCH 1 population (n = 132) was identified. The MONARCH 1 (n = 108) cohort was matched to the real-world chemotherapy cohort (n = 108). Median OS was 22.3 months in the abemaciclib arm versus 13.6 months in the matched real-world chemotherapy cohort with an estimated hazard ratio (HR) of 0.54. The median DoT was 4.1 months in MONARCH 1 compared to 2.9 months in the real-world chemotherapy cohort with HR of 0.76. Conclusions This study demonstrates an approach to create a real-world chemotherapy cohort suitable to serve as a comparator for trial data. These exploratory results suggest a survival advantage and place the benefit of abemaciclib monotherapy in clinical context.This study was funded by Eli Lilly and Company