Experiences of oncology researchers in the Veterans Health Administration during the COVID-19 pandemic.

The Veterans Health Administration is chartered "to serve as the primary backup for any health care services needed…in the event of war or national emergency" according to a 1982 Congressional Act. This mission was invoked during the COVID-19 pandemic to divert clinical and research resources. We used an electronic mixed-methods questionnaire constructed using the Theoretical Domains Framework (TDF) and the Capability, Opportunity, and Motivation (COM-B) model for behavior change to study the effects of the pandemic on VHA researchers. The questionnaire was distributed electronically to 118 cancer researchers participating in national VHA collaborations. The questionnaire received 42 responses (36%). Only 36% did not feel that their research focus changed during the pandemic. Only 26% reported prior experience with infectious disease research, and 74% agreed that they gained new research skills. When asked to describe helpful support structures, 29% mentioned local supervisors, mentors, and research staff, 15% cited larger VHA organizations and 18% mentioned remote work. Lack of timely communication and remote work, particularly for individuals with caregiving responsibilities, were limiting factors. Fewer than half felt professionally rewarded for pursuing research related to COVID. This study demonstrated the tremendous effects of the COVID-19 pandemic on research activities of VHA investigators. We identified perceptions of insufficient recognition and lack of professional advancement related to pandemic-era research, yet most reported gaining new research skills. Individualizing the structure of remote work and ensuring clear and timely team communication represent high yield areas for improvement.

Differential Efficacy of Anti-VEGF Antibodies Based on Sex and Race in a Diverse Cohort of Advanced Nonsquamous Non-Small Cell Lung Cancer.

OBJECTIVES: Bevacizumab with chemotherapy improved overall survival (OS) in the E4599 trial in metastatic nonsquamous non-small cell lung cancer (NS-NSCLC). A meta-analysis demonstrated an OS benefit with bevacizumab only in a subset of nonwhite patients. We explored the efficacy of antivascular endothelial growth factor antibodies (AVA) in a diverse cohort. MATERIALS AND METHODS: Patients with advanced (stage IIIB/IV, American Joint Committee Cancer 7th edition) recurrent or metastatic NS-NSCLC diagnosed January 2006 to December 2017 at a single medical center were included. Survival analysis was performed with log-rank testing of the Kaplan-Meier estimator. Univariate models were constructed, and significant variables, age, sex, race were incorporated into a multivariate Cox proportional hazard model. Data analysis was performed on SAS. RESULTS: A total of 171 patients, 80 were treated with AVA and 91 were untreated. Median age: 63 years, 55% females, 19% non-Hispanic whites, 44% blacks and 32% Hispanic whites; median 40 pack-years of smoking; 11.7% had sensitizing epidermal growth factor receptor mutations. Patients who received AVA had a survival benefit (26.6 vs. 19 mo, P=0.025). Adjusting for age, sex, race/ethnicity, epidermal growth factor receptor mutations, Eastern Cooperative Oncology Group performance status and number of metastases; AVA therapy was associated with improved OS (adjusted hazard ratio=0.62; P=0.049). In a subgroup analysis, females had survival benefit with AVA (median survival: 29.1 vs. 14.2 mo, log-rank P=0.02) which was significant in the adjusted model (adjusted hazard ratio=0.52; P=0.049). CONCLUSIONS: In a diverse cohort of patients with advanced NS-NSCLC, a survival benefit was confirmed with AVA. The greatest magnitude of benefit was in blacks and non-Hispanic whites. A significant survival benefit was limited to female patients.

Emerging drugs for EGFR-mutated non-small cell lung cancer.

INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent the standard of care for patients with metastatic non-small-cell lung cancer (NSCLC) harboring sensitizing EGFR mutations. However, these agents are associated with inevitable treatment resistance. Newer generations of TKIs are under development that may prevent or overcome resistance and enhance intracranial activity. Areas covered: In this review, we will discuss newer generations of EGFR TKIs for EGFR-mutated NSCLC. We will also address resistance mutations and escape pathways associated with these agents such as secondary mutations, downstream signaling, bypass pathways, phenotypic transformation, anti-apoptotic signaling, immune evasion, and angiogenesis. Furthermore, this article encompasses emerging data from combination trials with next-generation TKIs that are being pursued to delay or prevent the occurrence of resistance. Expert opinion: The promise and challenge of precision oncology is encapsulated in the treatment of EGFR-mutated NSCLC with TKIs. Third generation TKIs have shown superior efficacy in the front-line setting and have become standard of care. A better understanding of mechanisms of treatment failure and disease relapse will be required to develop novel therapeutic strategies to further improve patient outcomes in the future.