Similar Efficacy Observed for First-Line Immunotherapy in Racial/Ethnic Minority Patients With Metastatic NSCLC.

BACKGROUND: Limited data exist on the impact of immunotherapy use in ethnic minority patients with non-small cell lung cancer (NSCLC), because they have been underrepresented in immunotherapy trials. This study aims to evaluate race/ethnicity and other demographic, socioeconomic, and clinical factors of patients with metastatic NSCLC treated with first-line immunotherapy. METHODS: A retrospective cohort study of 5,920 patients diagnosed with lung cancer treated at Montefiore Einstein Cancer Center from January 1, 2013, to June 1, 2022, was used to identify patients with metastatic NSCLC without EGFR, ALK, or ROS1 alterations who underwent first-line immunotherapy (n=248). The primary endpoint was overall survival (OS), with secondary endpoints of progression-free survival (PFS) and time to discontinuation (TTD) from the start of immunotherapy. RESULTS: Among the 248 patients, median follow-up time was 12.0 months, median age at start of treatment was 66 years, and 39.1% were non-Hispanic Black, 30.2% were Hispanic, and 30.7% were non-Hispanic White. OS (P=.39), PFS (P=.29), and TTD (P=.98) were similar among racial/ethnic groups. Patients with an ECOG performance status (PS) of <2 at the start of immunotherapy had longer OS compared with those with ECOG PS of ≥2 (P<.0001). PD-L1 expression (<50% vs ≥50%; P=.03) and body mass index (BMI) (P=.01) were also found to be associated with PFS, and ECOG PS (P<.0001) and BMI (P=.02) were associated with TTD. In a multivariate analysis of OS and PFS, ECOG PS was the only variable found to be significant. CONCLUSIONS: Our study observed similar benefits of immunotherapy in patients with metastatic NSCLC in different racial and ethnic groups. Furthermore, ECOG PS was associated with OS, and PD-L1 expression and BMI were associated with PFS and TTD. These findings help identify potential factors associated with outcomes and care while patients are undergoing immunotherapy.

Intracranial Outcomes of De Novo Brain Metastases Treated With Osimertinib Alone in Patients With Newly Diagnosed EGFR-Mutant NSCLC.

Introduction: Patients with EGFR-mutant NSCLC have a high incidence of brain metastases. The EGFR-directed tyrosine kinase inhibitor osimertinib has intracranial activity, making the role of local central nervous system (CNS)-directed therapies, such as radiation and surgery, less clear. Methods: Patients with EGFR-mutant NSCLC and brain metastases who received osimertinib as initial therapy after brain metastasis diagnosis were included. Individual lesion responses were assessed using adapted RANO-BM criteria. CNS progression and local progression of brain metastasis from osimertinib start were analyzed using cumulative incidence treating death as a competing risk. Overall survival was estimated using Kaplan-Meier methodology. Results: There were 36 patients who had a median interval from brain metastasis diagnosis to first-line osimertinib initiation of 25 days. In total, 136 previously untreated brain metastases were tracked from baseline. Overall, 105 lesions (77.2%) had complete response and 31 had partial response reflecting best objective response of 100%. Best response occurred at a median of 96 days (range: 28-1113 d) from baseline magnetic resonance imaging. This reflects a best objective response rate of 100%. Two-year overall survival was 80%. CNS progression rates at 1-, 2-, and 3-years post-osimertinib were 21%, 32%, and 41%, respectively. Lesion-level local failure was estimated to be 0.7% and 4.7% at 1- and 2-years post-osimertinib, respectively. No clinicodemographic factors including brain metastasis number were associated with post-osimertinib progression. Conclusions: Intracranial response to osimertinib is excellent for patients with EGFR-mutant NSCLC with de novo, previously untreated brain metastases. Very low local failure rates support a strategy of upfront osimertinib alone in selected patients.

Lung Cancer in Never Smokers: Delving into Epidemiology, Genomic and Immune Landscape, Prognosis, Treatment, and Screening.

Lung cancer in never smokers (LCINS) represents a growing and distinct entity within the broader landscape of lung malignancies. This review provides a comprehensive overview of LCINS, encompassing its epidemiologic trends, risk factors, distinct genomic alterations, clinical outcomes and the ongoing initiative aimed at formulating screening guidelines tailored to this unique population. As LCINS continues to gain prominence, understanding its intricate genomic landscape has become pivotal for tailoring effective therapeutic strategies. Moreover, LCINS does not meet the criteria for lung cancer screening as per the current guidelines. Hence, there is an urgent need to explore its heterogeneity in order to devise optimal screening guidelines conducive to early-stage detection. This review underscores the vital importance of detailed research to elucidate the multifaceted nature of LCINS, with the potential to shape future clinical management and screening recommendations for this unique and growing patient cohort.

Navigating and diagnosing cognitive frailty in research and clinical domains.

While physical frailty has been recognized as a clinical entity for some time, the concept of cognitive frailty (CF) is now gaining increasing attention in the geriatrics research community. CF refers to the co-occurrence of physical frailty and cognitive impairment in older adults, which has been suggested as a potential precursor to both dementia and adverse physical outcomes. However, this condition represents a challenge for researchers and clinicians, as there remains a lack of consensus regarding the definition and diagnostic criteria for CF, which has limited its utility. Here, using insights from both the physical frailty literature and cognitive science research, we describe emerging research on CF. We highlight areas of agreement as well as areas of confusion and remaining knowledge gaps, and provide our perspective on fine-tuning the current construct, aiming to stimulate further discussion in this developing field.

Characterization of Central Nervous System Clinico-Genomic Outcomes in ALK-Positive Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Alectinib.

INTRODUCTION: Highly effective brain-penetrant ALK-targeted tyrosine kinase inhibitors (TKIs) have been developed for the management of NSCLC patients with brain metastases (BM). Local therapy (LT) such as SRS or therapeutic craniotomy is increasingly being deferred for such patients. Herein we report detailed patient- and lesion-level intracranial outcomes and co-mutational genomic profiles from a cohort of NSCLC patients with BM treated with alectinib, with or without LT. METHODS: We retrospectively reviewed ALK fusion-positive NSCLC patients with BMs who received alectinib at the diagnosis of BM from 1/2012 and 5/2021. Outcome variables included intracranial progression-free survival (iPFS), overall survival (OS), duration of TKI therapy, and CNS response rates. Genomic characteristics from tumor specimens were assessed with MSK-IMPACT, a next-generation sequencing (NGS)-based genomic profiling assay. RESULTS: A total of 38 patients with 114 CNS lesions were included. Twelve of these patients also received contemporaneous LT (SRS, WBRT, or surgical resection). Maximal BM diameter in the TKI + LT group was greater (p < 0.003) but despite this difference, iPFS (TKI only, HR 1.21, 95 % CI 0.51-2.89; p = 0.66) and OS (TKI only, HR 5.99, 95 % CI 0.77-46.6; p = 0.052) were similar between groups and trended towards more favorable outcomes with the addition of LT. SMARCA4 co-alterations were associated with inferior OS (HR 8.76, 1.74-44.2; p = 0.009). CONCLUSIONS: Our study demonstrated that patients with ALK fusion-positive NSCLC treated with TKI + LT had larger BM and higher likelihood of pre-treatment neurologic symptoms. Despite these differences, iPFS was similar between groups. Results should be interpreted with caution as our study was limited by an underpowered sample size. SMARCA4 co-alterations were associated with inferior OS and these findings warrant further investigation.

Advances in the Management of Central Nervous System Metastases in Non-Small Cell Lung Cancer.

Central nervous system (CNS) metastases are common among patients with non-small cell lung cancer (NSCLC). While the presence of brain metastases has historically portended poor prognosis, recent advances in local and systemic therapies have greatly improved outcomes for NSCLC patients with CNS involvement. Stereotactic radiology surgery (SRS) has emerged as an effective radiotherapy technique with fewer toxicities compared to whole brain radiotherapy (WBRT). Furthermore, multi-generation tyrosine kinase inhibitors (TKIs) with CNS overall response rates (ORR) of up to 70-80% are now an accepted first-line approach for a subset of advanced NSCLC patients with targetable molecular alterations. In addition, while the CNS was once considered an immunologic sanctuary site, growing evidence shows that immune checkpoint inhibitors (ICIs) can induce durable responses in brain metastases as well. Ongoing efforts to optimize CNS metastases management are necessary to refine multimodal treatment approaches and develop new therapeutics with better CNS penetrance.

Hypothesized Explanations for the Observed Lung Cancer Survival Benefit Among Hispanics/Latinos in the United States.

Hispanic/Latino ethnicity is associated with improved survival from non-small cell lung cancer compared to that for non-Hispanic Whites even though Hispanics/Latinos are more likely to potentially have inferior access-to-care and experience greater health disparities. To this end, we conducted a literature review to identify possible explanations for this survival benefit, including the role of chronic obstructive pulmonary disease and cardiovascular diseases, genetic variation, cultural influences, and immigration factors. Overall, intermittent smoking patterns, genetic variation, co-morbidities, and cultural influences were all factors likely to partially explain this survival benefit. On the other hand, immigration factors, acculturation, and access-to-care were less likely to support the survival advantage. Future research should analyze relevant Hispanic/Latino subgroups (e.g., Mexican, Puerto Rican, Cuban, Dominican, Central American, South American) and specifically focus on the relationship between Hispanic/Latino ethnicity and different lung cancer subtypes. If the Hispanic/Latino mortality benefit observed in lung cancer truly exists, a better understanding of the underlying mechanism(s) may help extend these benefits to other ethnic and racial groups.

Metformin use and mortality and length of stay among hospitalized patients with type 2 diabetes and COVID-19: A multiracial, multiethnic, urban observational study.

Introduction: Diabetes mellitus is a common comorbidity among patients with coronavirus disease 2019 (COVID-19). Diabetic patients with COVID-19 have a two-fold increased risk of death and tend to have more severe infection compared to the general population. Metformin, a first-line medication for diabetes management, has anti-inflammatory and immunomodulatory effects. Previous studies focusing on metformin and COVID-19 clinical outcomes have had mixed results, with some showing a mortality benefit or decreased complications with metformin use. To date, few studies have analyzed such outcomes among a diverse, multiracial community. Methods: This was a retrospective review of patients with Type 2 diabetes and a confirmed COVID-19 infection admitted to an urban academic medical center from January 1, 2020 to May 7, 2020. Baseline characteristics were collected. The primary outcomes of the study were in-hospital mortality and length of stay (LOS). Results: A total of 4462 patients with Type 2 diabetes and confirmed COVID-19 were identified. 41.3% were Black, and 41.5% were Hispanic. There were 1021 patients in the metformin group and 3441 in the non-metformin group. Of note, more participants in the metformin group had comorbid disease and/or advanced diabetes. We found no statistically significant differences between the metformin and non-metformin group in in-hospital mortality (28.1% vs 25.3%, P=0.08) or length of hospital stay in days (7.3 vs. 7.5, P=0.59), even after matching patients on various factors (29.3% vs. 29.6%, P=0.87; 7.7 vs. 8.1, P=0.23). Conclusion: While patients had more comorbid disease and advanced diabetes in the metformin group, there were no significant differences with regard to in-hospital mortality or length of stay due to COVID-19 compared to the non-metformin group. Prospective studies are needed to determine if there is clinical benefit for initiating, continuing, or re-initiating metformin in patients hospitalized with COVID-19.

Prevalence and Assessment of Factors Associated with COVID-19 Vaccine Hesitancy in an Ethnic Minority Oncology Patient Population.

BACKGROUND: Complicating the COVID-19 pandemic are the healthcare disparities experienced by ethnic minorities, especially those with comorbidities including cancer. The introduction of COVID-19 vaccines has been instrumental in blunting the morbidity and mortality from the pandemic; however, vaccine hesitancy, particularly among ethnic minorities, has been a major concern. Thus, we sought to evaluate the knowledge and perspectives of COVID-19 and vaccines among our ethnic minority cancer patient population. METHODS: Following an IRB approved protocol, questionnaires were completed by patients in a predominantly ethnic minority population at a single institution between 1 February and 30 June 2021. Included were any adult cancer patients with either a solid or hematologic malignancy. RESULTS: Among the 84 patients that were offered the questionnaires, 52 patients responded, with a median age of 63.5 years. Overall, 36% were non-Hispanic Blacks and 30% were Hispanics; 65% were receiving active treatment for their cancer. Seventy-nine percent believed COVID-19 to be dangerous or harmful to them, 61% were concerned about the side effects, yet 65% considered COVID-19 vaccines as safe. Among the seven patients that refused the vaccine, (71%, n = 5) cited side effects and/or (57%, n = 4) believed that the vaccine was not needed. Overall, there was a significantly higher chance of being vaccinated if patients were receiving active cancer treatment, believed COVID-19 was harmful, or that the vaccine was safe, and knew COVID-19 was a virus. CONCLUSIONS: This exploratory study demonstrates that most ethnic minority cancer patients are receptive to vaccines, with a majority being vaccinated. However, we also discovered various reasons why this group of patients may not want be vaccinated, including concerns about side effects and perception that COVID-19 is not harmful. These findings can help us further understand the complex nature of vaccine hesitancy in ethnic minority cancer patients, and aid in developing future vaccine awareness strategies as the COVID-19 pandemic continues to evolve.

A real world analysis of first line treatment of advanced EGFR mutated non-small cell lung cancer: A multi-center, retrospective study.

INTRODUCTION: The recently published FLAURA trial demonstrated that osimertinib has remarkable efficacy in front-line setting for non-small cell lung cancer (NSCLC). While this has transformed current practice, there are no effective treatments following progression on osimertinib. The aim of our study was to compare progression-free survival (PFS) and overall survival (OS) between patients initiated on osimertinib to those started on other EGFR TKIs. METHODS: This was a multicenter, retrospective study conducted at two large academic centers. Adult patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received EGFR therapy between 2014 and 2019 were included. Patients were dichotomized based on front-line TKI (osimertinib vs. other). PFS, OS, and time-to-discontinuation were evaluated. RESULTS: One-hundred seventy-two patients were included in the final analysis. Fifty-two (30.2%) patients received osimertinib and 120 (69.8%) patients received another EGFR TKI. The PFS rates at 6, 12, and 18 months were 86.3%, 79.5%, 69.8% in the osimertinib group and 86.6%, 64.2%, 39.3% in the other EGFR TKI group, respectively (p < 0.0036).Estimated OS at 6, 12, and 18 months was similar for both groups: 94.2%, 94.2%, 80.2% and 95.7%, 93.9%, 84.1%, respectively [Adjusted HR = 0.95 (95% CI, 0.37-2.44; p < 0.9128]. CONCLUSION: Osimertinib demonstrated greater 12 and 18 month PFS compared to other EGFR TKIs. This finding is consistent with results of the FLAURA trial. However, unlike FLAURA, there were no differences in estimated OS between the two groups in our study. Further research to evaluate optimal sequencing strategies in the real world of first, second and third generation TKIs is needed.

Clinical efficacy with dabrafenib and trametinib in a T599_V600insT poorly differentiated metastatic thyroid carcinoma.

BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen-activated protein kinase kinase) inhibitors have been shown to improve clinical outcomes in tumours presenting with mutations in the BRAF gene. The most common form of BRAF mutation is V600E/K and has been shown to occur in thyroid cancers. Treatment data for patients harbouring less frequent BRAF mutations are limited. In vitro studies have shown that mutations in codons 599-601 increase kinase activity similar to that in V600E mutations, which suggests that BRAF and MEK inhibitors could be an effective treatment option. Here, we report a case of a patient with thyroid carcinoma harbouring a rare amino acid insertion in codon 599 of the BRAF gene (T599_V600insT) treated with a BRAF and MEK inhibitor.

Impact of Tyrosine Kinase Inhibitor Starting Dose on Outcomes in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) can cause intolerable adverse events in patients with non-small cell lung cancer (NSCLC) and may be prescribed at a lower dose. OBJECTIVE: Our objective was to analyze the starting doses of oral EGFR and ALK TKIs in patients diagnosed with NSCLC at our institution. METHODS: We conducted a retrospective chart review with patients on EGFR and ALK TKIs for NSCLC. Patients were categorized into 2 groups: patients initiated on Food and Drug Administration (FDA) standard dose (SD) and patients initiated on a reduced dose (RD). Progression-free survival (PFS), overall survival (OS) and other treatment outcomes were compared between both groups. RESULTS: Ninety patients were included for analysis. The median time-to-progression for the SD group (n = 67) and RD group (n = 23) were 13.4 months (95% confidence interval [CI]:8.9-15.6) and 15.1 months (95%CI: 5.6-21.5), respectively. Median time-to-death was not estimable for OS. The predicted OS probability at approximately 15 months post treatment initiation for the SD group and RD group was 81.8% and 80.5%, respectively. CONCLUSION: Patients who initiated TKI therapy at a RD did not have different PFS and 15-month survival outcomes than patients who initiated TKI therapy at the FDA SD.

A Comprehensive Review of Contemporary Literature for Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer and Their Toxicity.

Mutations in the epidermal growth factor receptor (EGFR) are common amongst those with non-small cell lung cancer and represent a major factor in treatment decisions, most notably in the advanced stages. Small molecule tyrosine kinase inhibitors (TKIs) that target the EGFR, such as erlotinib, gefitinib, icotinib, afatinib, dacomitinib and osimertinib, have all shown to be effective in this setting. Osimertinib, a third-generation EGFR TKI, is a favorable option, but almost all patients develop resistance at some time point. There are no effective treatment options for patients who progress on osimertinib, but ongoing trials will hopefully address this unmet need. The aim of this review is to provide a comprehensive review of the data with EGFR TKIs, management of the toxicities and the ongoing trials with this class of agents.