Electronic Medical Record-Based Nudge Intervention to Increase Comprehensive Molecular Genotyping in Patients With Metastatic Non-Small Cell Lung Cancer: Results From a Prospective Clinical Trial.

PURPOSE: Less than half of the patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) undergo comprehensive molecular testing. We designed an electronic medical record (EMR)-based "nudge intervention" to prompt plasma-based molecular testing at the time of initial medical oncology consultation. METHODS: A nonrandomized prospective trial was conducted at the University of Pennsylvania's academic practice and two affiliated community practices. Molecular genotyping was performed by tissue- and/or plasma-based next generation sequencing methods. Comprehensive testing was defined as testing for EGFR, ALK, BRAF, ROS1, MET, RET, KRAS, and NTRK. Guideline-concordant treatment was defined as the use of the appropriate first-line (1L) therapy as per the National Comprehensive Cancer Network (NCCN) guidelines. Proportion of patients with comprehensive molecular genotyping results available at any time, molecular results available before 1L therapy, and guideline-concordant 1L treatment were compared between the preintervention and postintervention cohorts using Fisher's exact test or Pearson's chi-squared test. RESULTS: Five hundred and thirty-three patients were included, 376 in the preintervention cohort and 157 in the postintervention cohort. After implementation of the EMR-based nudge, a higher proportion of patients underwent comprehensive molecular testing in the postintervention versus the preintervention cohort (100% v 88%, P = <.001), had results of comprehensive molecular testing available before initiating 1L treatment (97.3% v 91.6%, P = .026), and received NCCN guideline-concordant care (89.8% v 78.2%, P = .035). CONCLUSION: Across three practice sites in a large health system, implementation of a provider team-focused EMR-based nudge intervention was feasible, and led to a higher number of patients with NSCLC undergoing comprehensive molecular genotyping. These findings demonstrate that behavioral nudges can promote molecular testing and should be studied further as a tool to improve guideline-concordant care in both community and academic sites.

Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

INTRODUCTION: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab. METHODS: This is a randomized, phase II, multicenter study evaluating carboplatin, pemetrexed, bevacizumab with and without atezolizumab in 117 patients with stage IV nonsquamous NSCLC. Randomization is 2 to 1 favoring the atezolizumab containing arm. Eligible patients include: 1) those with tumors with sensitizing EGFR alterations in exons 19 or 21 or 2) patients who have never smoked and have wild-type tumors (ie, no EGFR, ALK or ROS1 alterations). Patients are defined as having never smoked if they have smoked less than 100 cigarettes in a lifetime. Patients with EGFR-mutated tumors must have disease progression or intolerance to prior tyrosine kinase inhibitor (TKI) therapy. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate, duration of response, and time to response. CONCLUSION: This phase II trial is accruing patients at U.S. sites through the National Comprehensive Cancer Network (NCCN). The trial opened in August 2019 and accrual is expected to be completed in the Fall of 2024.

Association Between Availability of Molecular Genotyping Results and Overall Survival in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer.

PURPOSE: Current guidelines recommend molecular genotyping for patients newly diagnosed with metastatic nonsquamous (mNSq) non-small-cell lung cancer (NSCLC). The association between availability of molecular genotyping before first line (1L) therapy and overall survival (OS) is not known. METHODS: We conducted a real-world cohort study using electronic health records in patients newly diagnosed with mNSq NSCLC. Cox proportional-hazards multivariable regression models were constructed to examine the association between OS and test result availability before 1L therapy, adjusting for covariates. Additional analyses were conducted to assess the consistency and strength of the relationship. Multivariable logistic regression models were used to examine the association between concurrent tissue and plasma testing (v tissue alone) and result availability. RESULTS: Three hundred twenty-six patients were included, 80% (261/326) with results available before 1L (available testing group), and 20% (65/326) without results available (unavailable testing group). With 14.2-month median follow-up, patients in the available testing group had significantly longer OS relative to the unavailable testing group (adjusted hazard ratio, 0.43; 95% CI, 0.30 to 0.62; P < .0001). The adjusted odds of availability of results before 1L therapy was higher with concurrent tissue and plasma testing (v tissue testing alone; adjusted odds ratio, 2.06; 95% CI, 1.09 to 3.90; P = .026). CONCLUSION: Among patients with mNSq NSCLC in a real-world cohort, availability of molecular genotyping results before 1L therapy was associated with significantly better OS. Concurrent tissue and plasma testing was associated with a higher odds of availability of results before 1L therapy. These findings warrant renewed attention to the completion of molecular genotyping before 1L therapy.