PURPOSE: Newer-generation tyrosine kinase inhibitors (TKIs) for non–small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR ) mutations and anaplastic lymphoma kinase ( ALK ) rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited. MATERIALS AND METHODS: Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States. Time-to-CNS progression and overall survival (OS) were analyzed, with multivariable adjustment in Fine & Gray and Cox proportional hazards models for clinically relevant factors. RESULTS: From 2013 to 2022, 317 patients were identified (200 TKI-only and 117 TKI + SRS). Two hundred fifty (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients receiving TKI + SRS were more likely to have BM ≥1 cm ( P < .001) and neurologic symptoms ( P < .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41 v 40 months, respectively; P = .5). On multivariable analysis, TKI + SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR], 0.63 [95% CI, 0.42 to 0.96]; P = .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55]; P < .001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI + SRS in patients with BM ≥1 cm in diameter for time-to-CNS progression and CNS progression-free survival. CONCLUSION: The addition of up-front SRS to CNS-penetrant TKI improved time-to-CNS progression and local CNS control, but not OS, in patients with BM from EGFR - and ALK-driven NSCLC. Patients with larger BM (≥1 cm) may benefit the most from up-front SRS.

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.

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.

E18692 Background: Immunotherapy (IO) has become an essential component in the treatment of NSCLC. However, there is limited data on the clinical impact of IO in distinct ethnic minorities who have been greatly under-represented in previous IO trials. It remains unclear whether Black patients carry similar characteristics and responses compared to Non-Black patients. Methods: Patients who were diagnosed with NSCLC from 1/1/2013 to 12/31/18 and confirmed to have received IO were identified from the Montefiore cancer network. Black and Non-Black patients’ characteristics were compared in patient clinical and socioeconomic variables by chi-squared, Mann-Whitney tests and two sample t-tests. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier survival analysis and log-rank analysis using R 4.1.2 version. Results: Of the 108 patients that were analyzable, overall median age was 67 (range 45-86) years old, 35% were Black, 80% smokers/former smokers, 73% were metastatic, 53% treated with PD-l/PD-L1 inhibitor-based IO alone and 65% on first-line immunotherapy regimens. PD-L1 testing were performed in 88 (81%) of patients, including 33 (87%) Black and 55 (79%) Non-Blacks. PD-L1 TPS≥1% was found in 26 (68%) of Blacks and 42 (60%) of Non-Blacks but no significant difference between the two groups (p = 0.792). Overall, median follow-up time was 19.7 months, 50% of patients had disease control with either a complete/partial response or stable disease within 3 months of starting IO but again was not significantly different between Black and Non-Black patients (p = 0.591). Furthermore, there was no significant difference in PFS (8.2 vs. 6.2 months, p = 0.210) and OS (10.9 vs. 9.8 months, p = 0.438). Nevertheless, there was a significantly longer duration of IO in the Blacks (median 7.4 months) compared to the Non-Blacks (3.9 months) (p = 7.17E-07) (Table). Conclusions: Although the response and survival outcomes of IO were not significantly different between Black and Non-Black patients, the duration of IO is significantly longer in Black patients. This finding warrants further exploration on the reasoning behind this which may include different toxicity, tolerability or physiological characteristics.