Background Osimertinib is recommended for patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. However, there are few reports assessing the efficacy of osimertinib in elderly patients or comparing osimertinib to gefitinib, which is recommended for the elderly. Methods We retrospectively reviewed the records of elderly patients (>75 years old) who received osimertinib or gefitinib as first-line treatment for NSCLC harboring EGFR mutations between April 2010 and December 2022. Treatment efficacy and toxicities between the two treatment groups (Osimertinib group [Osime group] vs. Gefitinib group [Gef group]) were compared. Additionally, the efficacy and toxicities in patients over 80 years old were also assessed. Results A total of 204 patients (Osime group = 93 and Gef group = 111) were assessed. No significant differences in age, sex, smoking status, ECOG performance status, and EGFR mutation subtype between the two groups were found. There was no significant difference in median overall survival time (MST) (27.8 months in the Osime group and 20.6 months in the Gef group; p-value = 0.12) or frequency of treatment discontinuation, interruption, and dose reduction. For patients aged >80 years old, no significant difference in MST (24.0 months in the Osime group and 20.4 months in the Gef group; p-value = 0.12) was also observed. Conclusions In elderly NSCLC patients harboring EGFR mutations, no statistically significant differences in survival outcomes were observed between osimertinib and gefitinib, although numerically longer PFS and OS were observed with osimertinib. Gefitinib may remain a reasonable treatment option in this population.

Background For patients suffering from intractable cancer pain, which cannot be sufficiently relieved even with strong opioid analgesics, methadone is recommended in Japan. However, the real-world data on the efficacy and safety of methadone for intractable pain in patients with lung cancer remain scarce in clinical setting. The aim of this clinical study was to investigate the efficacy and safety of methadone for intractable pain in advanced lung cancer patients. Methods All the cases of advanced lung cancer patients who were administered methadone for intractable pain at the Shizuoka Cancer Center between September 2014 and December 2022 were extracted, and their medical information in the electronic medical records were examined. We investigated pain intensity in Numeric Rating Score (NRS) on the day before and 5 days after the initiation of methadone administration, when methadone blood levels were expected to reach a plateau. In addition, the adverse events possibly caused by methadone were also investigated. Results and conclusions Methadone was prescribed for intractable pain in 37 patients with advanced lung cancer during the study period. The leading cause of intractable pain was bone metastasis (including invasion). Both the pain intensity in NRS and the number of rescue doses were significantly reduced by the introduction of methadone (P < .001). In only two patients, methadone was discontinued due to the side effects thought to be caused by this drug. The results of this study indicated the favorable efficacy and safety profile of methadone for intractable pain in patients with advanced lung cancer.

BACKGROUND:Daily low-dose carboplatin with concurrent thoracic radiotherapy is the standard treatment for older patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) in Japan. METHODS:This open-label phase 3 trial was conducted at 38 institutions in Japan. Patients aged ≥ 75 years with LA-NSCLC were randomly assigned (1:1) to receive daily carboplatin (30 mg/m2) or weekly carboplatin (area under the curve, 2 mg·min/mL) plus nab-paclitaxel (30 mg/m2) with thoracic radiotherapy. Durvalumab maintenance therapy was recommended after treatment completion. The primary endpoint was overall survival, which was used to assess the non-inferiority of weekly carboplatin plus nab-paclitaxel compared to daily low-dose carboplatin. RESULTS:From December 2020 to March 2024, 124 patients were enrolled (carboplatin arm, 61 and carboplatin plus nab-paclitaxel arm, 63). In the planned interim analysis, the Bayesian predictive probability indicating the non-inferiority of carboplatin plus nab-paclitaxel compared with carboplatin in the final analysis was 8.0%, leading to early study termination for futility. The median overall survival was not estimable in the carboplatin arm; the estimated value in the carboplatin plus nab-paclitaxel arm was 26.1 months (hazard ratio, 1.56; 95% confidence interval, 0.79-3.11; p = 0.200). Two treatment-related and seven non-cancer-related deaths occurred in the carboplatin plus nab-paclitaxel arm. Patients in the carboplatin arm had better quality of life than those in the carboplatin plus nab-paclitaxel arm at 6 weeks (odds ratio, 0.39; 95% confidence interval, 0.18-0.81; p = 0.012). CONCLUSIONS:Daily low-dose carboplatin with concurrent thoracic radiotherapy remains the standard treatment for older patients with unresectable LA-NSCLC in Japan.

Pain intensity is typically assessed using qualitative scales, including the numerical rating scale (NRS), which has limitations in quantifying pain intensity. PainVision® PS-2100 (Nipro Corporation, Osaka, Japan) was developed to quantify pain as pain degree (PD); however, its ability to assess acute postoperative pain remains unclear. This prospective single-center pilot study aimed to evaluate the performance of PainVision® by comparing PD with NRS scores after lung resection surgery. Fifty patients who underwent lobectomy or segmentectomy for lung tumors were enrolled. PD and NRS scores were measured twice daily, at rest and during mobilization, on postoperative days (PODs) 1, 2, 5, and 7. The correlation coefficient between PD and NRS scores on POD 1 was the primary endpoint. Secondary endpoints included the correlation coefficients on PODs 2, 5, and 7; the overall correlation coefficient across all measured data; and a comparison of postoperative trends in PD and NRS scores. On POD 1, statistically significant weak-to-moderate positive correlations were observed between PD and NRS scores (r = 0.363–0.634, p < 0.05). Similar results were observed on PODs 2, 5, and 7 in most measurement conditions (r = 0.274–0.664). A statistically significant moderate correlation was observed across all measurements (n = 736; r = 0.575, p < 0.001). PD and NRS scores showed similar trends: values on POD 2 were comparable to POD 1, whereas PODs 5 and 7 were significantly lower. PainVision® may be a feasible tool for quantifying acute postoperative pain following lung resection.

Abstract Background & Aims: The BRAF V600E mutation occurs in approximately 8-12% of colorectal cancers (CRC) and confers poor prognosis and therapeutic resistance. Despite the clinical success of combined BRAF and EGFR inhibition in the BEACON trial, resistance rapidly develops. Adenosine-to-inosine RNA editing, which is a post-transcriptional modification driven by adenosine deaminase acting on RNA (ADAR), promotes tumor malignancy and the acquisition of metastatic potential. We previously reported that ADAR1-high macrophages act as mediators of drug resistance and proposed ADAR1-targeted therapy as a potential new approach (Molecular Cancer, 2025). However, the specific patient population likely to benefit from ADAR1-targeted therapy remains unclear. This study investigated whether secreted BRAF V600E protein induces ADAR1-dependent RNA editing to promote tumor progression and therapeutic resistance, and whether JAK inhibition can enhance the efficacy of BRAF/EGFR-targeted therapy. Methods: We combined analysis of clinical CRC tissues, spatial transcriptomics, and RNA sequencing with functional in vitro and in vivo models to characterize BRAF V600E secretion, intracellular distribution, and downstream molecular effects. Pharmacologic inhibition using JAK, EGFR, and BRAF inhibitors was used to evaluate their effects on the ADAR1-RNA editing pathway and associated tumor phenotypes. Results: BRAF V600E-mutant CRC cells secreted the mutant BRAF protein through extracellular vesicles and soluble forms that were detectable in systemic circulation and distant tissues. ADAR1 expression was significantly higher in BRAF-mutant vs. BRAF-wild CRC (p<0.001). Stromal macrophages and fibroblasts internalizing extracellular BRAF V600E exhibited robust ADAR1 induction and hyper-RNA editing via type I interferon-JAK/STAT signaling, promoting immunosuppressive and tumor-supportive phenotypes. Wild-type tumor cells exposed to BRAF V600E protein upregulated ADAR1 and displayed enhanced proliferation and invasion, suggesting horizontal transfer of malignant traits. While combined BRAF/EGFR inhibition in HT29 and Colo205 cells suppressed direct oncogenic signaling, it paradoxically activated the JAK/STAT-ADAR1 axis, increasing RNA editing and resistance. Co-treatment with JAK inhibitors mitigated this effect, restored sensitivity, and suppressed tumor growth in preclinical models. Conclusions: Our findings define a novel circulating ‘BRAF-ADAR1-RNA editing’ axis that contributes to immune evasion and resistance in BRAF-mutant CRC. Dual targeting of this pathway, through JAK or ADAR1 inhibition in combination with BRAF/EGFR blockade, represents a rational therapeutic strategy to overcome refractory, mutation-driven colorectal cancer. Citation Format: Toshiaki Takahashi, Kunitoshi Shigeyasu, Kazuya Moriwake, Masashi Kayano, Hibiki Umeda, Kazuhiro Yoshida, Sho Takeda, Yuki Matsumi, Hiroyuki Kishimoto, Tomokazu Fuji, Kazuya Yasui, Hideki Yamamoto, Kosei Takagi, Hiroyuki Michiue, Yoshiko Mori, Fuminori Teraishi, Hiroshi Tazawa, Yuzo Umeda, Ajay Goel, Toshiyoshi Fujiwara. Secreted BRAF V600E drives ADAR1-dependent RNA editing and defines a therapeutic vulnerability in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3193.

Dysferlinopathy is an adult-onset form of muscular dystrophy caused by mutations in the dysferlin gene and is inherited in an autosomal recessive manner. Dysferlin is primarily known for its role in plasma membrane repair. Although several proteins associated with dysferlin have been identified, many aspects of its signaling pathways and protein-protein interactions remain unclear. Here, we focused on the region between the third and fourth C2 domains, where frequent genetic mutations occur and functional domains are concentrated, and identified the protein kinase CK2α (formerly known as casein kinase 2) as a novel dysferlin-binding protein. CK2α was found to accumulate at membrane injury sites along with dysferlin in mouse skeletal muscle, and membrane repair was delayed in CK2α knockout cells. Furthermore, overexpression of CK2α in dysferlin-deficient mouse muscle led to improved membrane repair. Additionally, we revealed that CK2α plays a role in phosphorylating annexin A1, which is known to bind to dysferlin and is involved in plasma membrane repair. Our results indicated that CK2α controls membrane repair by participating in the phosphorylation of annexin A1. The molecular interplay among dysferlin, CK2α, and phosphorylated annexin A1 represents a novel therapeutic target for promoting membrane repair.

ABSTRACT Background The efficacy of osimertinib in patients with postoperative recurrent non–small‐cell lung cancer (NSCLC) compared to those with Stage IV NSCLC harboring epidermal growth factor receptor (EGFR) mutations remains unclear. Methods This study evaluated the efficacy of osimertinib in patients with postoperative recurrent EGFR‐mutated NSCLC. We retrospectively evaluated patients with NSCLC harboring EGFR mutations (exon 19 deletion or L858R mutation) who received osimertinib between September 2018 and July 2022 at a single institution. The efficacy of osimertinib was compared between patients with postoperative recurrent NSCLC (postoperative group) and those with Stage IV NSCLC (Stage IV group). Results Among a total of 172 patients treated with osimertinib, 52 were classified into the postoperative group and 120 into the Stage IV group. The response rate (58.1% vs. 61.8%, p = 0.836) and progression‐free survival (hazard ratio [HR]: 0.854, 95% confidence interval [CI]: 0.558–1.306, p = 0.465) were not significantly different between the postoperative and Stage IV groups. Overall survival (OS) was significantly longer in the postoperative group than in the Stage IV group (median: 39.2 months and 28.5 months, respectively; HR: 0.521, 95% CI: 0.293–0.927, p = 0.024). In the multivariable analysis of OS, postoperative recurrent disease and performance status were independent favorable prognostic factors. Conclusions Postoperative recurrent disease was an independent favorable prognostic factor in patients with NSCLC harboring EGFR mutations treated with osimertinib.

Introduction Quantitative assessment of the pathologic response (pR) in the eyeball approach remains challenging. Few studies have clearly defined viable tumor cell regions (VTRs). We defined VTRs using AE1/AE3 (AE1/3) staining and examined the usefulness of computational pathology (CP) assessment of the pR after preoperative therapy (PT) in non-small cell lung cancer (NSCLC). Methods Among 50 NSCLC patients administered PT at our hospital between October 2002 and April 2021, we selected 31 cases that received PT and evaluated the correlations between AI-based and manual assessments of pR on a slide-by-slide in AE1/3 and hematoxylin and eosin (HE) stained slides. A total of 406 virtual slides (vs) were generated and divided into a training set (300 vs) and a test set (58 vs) without case duplication. pR was defined as the percent area of VTRs relative to the total tumor bed (TB) area. An experienced pathologist manually assessed the pR on HE slides and annotated TB regions, which were used to train a TB model. A VTR model was first developed on AE1/3 vs using an algorithm (AE1/3-trained VTR model), and the resulting labels were transferred to the HEvs to train a HE based VTR model (HE-trained VTR model). Results In the test set, AI assessed pR was strongly correlated with the manually assessed pR in the AE1/3 (Spearman’s ρ, 0.87, 95%CI, 0.74–0.94) and HE vs. (ρ 0.71, 95%CI, 0.49–0.86). Conclusion The AI-based CP platform appears to be feasible for quantitative evaluation of the pR following PT in cases of NSCLC.

The adverse prognostic impact of cancer cachexia is well recognized. We aimed to evaluate the prognostic impact of weight loss during first-line platinum-based chemo(immuno)therapy in patients with extensive-disease small-cell lung cancer (ED-SCLC). We retrospectively reviewed 187 of 346 ED-SCLC patients (54

TPS8676 Background: While EGFR tyrosine kinase inhibitors (TKIs) such as afatinib are standard treatments for patients with advanced non-small cell lung cancer (NSCLC) harboring uncommon or compound EGFR mutations (excluding exon 20 insertions and T790M), the duration of response is often limited, with a median progression-free survival (PFS) of approximately 8 to 10 months. Amivantamab is an EGFR mesenchymal–epithelial transition factor (MET) bispecific antibody with immune cell–directing activity that has multiple mechanisms of action as defined in preclinical models. For common EGFR mutated NSCLC, combination therapy with lazertinib has been approved in several countries based on its superiority in Phase III trial. Although a phase I study of amivantamab plus lazertinib combination therapy showed promising efficacy with a median PFS of 19.5 months in treatment-naïve patients with uncommon or compound EGFR mutations, this was a small-scale non-comparative study where efficacy was not the primary endpoint. The AGEHA study (WJOG17323L) is designed to prospectively evaluate whether amivantamab + lazertinib provides superior efficacy and acceptable safety compared to afatinib in patients with treatment-naïve, uncommon or compound EGFR mutated NSCLC. Methods: This multicenter, randomized, open-label, phase II trial is conducted by the West Japan Oncology Group (WJOG). Eligible patients are randomized in a 1:1 ratio to receive either combination therapy with amivantamab plus lazertinib in Arm A, or afatinib monotherapy in Arm B. The primary objective is to compare PFS between the two treatment arms. Secondary objectives include safety, overall response rate, and overall survival. Additionally, mandatory blood samples are collected at baseline and at the time of disease progression for comprehensive biomarker analysis using the Guardant Health platform to identify molecular predictors of response and resistance mechanisms, including approximately 740 gene alterations and methylation abnormalities. The target sample size is 70 patients (35 per arm). This study is designed with a one-sided alpha of 0.1 and a power of 80% to detect the superiority of amivantamab plus lazertinib over afatinib monotherapy. The primary analysis will compare PFS using a stratified log-rank test, and hazard ratios will be estimated using a Cox proportional hazards model. Key Eligibility Criteria: Patients must be histologically confirmed advanced or recurrent non-squamous NSCLC harboring uncommon or compound EGFR mutations, excluding exon 20 insertions and T790M. Participants must be treatment-naïve for advanced disease with an ECOG performance status of 0–1. Patient enrollment began in January 2026, with a recruitment period of two years and a total study duration of five years. Clinical trial information: jRCTs031250560 .

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are commonly used to manage diabetes and are known to cause weight loss. This study aimed to clarify whether SGLT2i-induced weight loss influences survival or toxicity during systemic therapy in patients with advanced non-small cell lung cancer (NSCLC) and comorbid diabetes. We conducted a retrospective analysis of patients with advanced NSCLC and diabetes who received first-line systemic therapy. Patients with an Eastern Cooperative Oncology Group performance status (PS) ≥ 3, driver mutations, interstitial lung disease, untreated diabetes, or missing data were excluded. We compared weight changes, progression-free survival (PFS), overall survival (OS), and adverse events between patients with and without SGLT2i. We defined cachexia as either 5

BACKGROUND:The LAURA study in unresectable stage III EGFR-mutated NSCLC without progression during/after chemoradiotherapy demonstrated significantly improved progression-free survival (PFS) with osimertinib versus placebo after definitive chemoradiotherapy. We report patient-reported outcomes (PROs) from LAURA. PATIENTS AND METHODS:Score changes from baseline (mixed model for repeated measures analysis) and time to confirmed deterioration in health-related quality of life (HRQoL), functioning and symptoms per EORTC QLQ-C30/LC13 questionnaires were analyzed. Tolerability was assessed using the PRO-CTCAE v1.0. RESULTS:Baseline EORTC scores were comparable between treatment arms. Risk of confirmed deterioration in key scales was generally not substantially different between arms (HR [95% CI], global health status/QoL 1.14 [0.74-1.78]; physical function 1.06 [0.65-1.71]; fatigue 1.23 [0.85-1.80]; appetite loss 1.00 [0.63-1.58]; dyspnea 1.30 [0.91-1.86]; coughing 1.17 [0.81-1.71]; pain in chest 1.46 [0.95-2.23]). Over 40 weeks, minimal changes from baseline were observed for key functioning/symptoms in both arms. PRO-CTCAE responses indicated similar tolerability of osimertinib versus placebo for symptom frequency and severity, except for loose/watery stools ("never"/"rarely" frequency vs. "never") and dry skin ("mild" severity vs. "none"). CONCLUSIONS:PRO scores were maintained during osimertinib treatment of unresectable stage III EGFR-mutated NSCLC after definitive chemoradiotherapy. Together with significant PFS benefit and expected, manageable safety, the PRO data support osimertinib treatment in this setting. TRIAL REGISTRATION NUMBER:NCT03521154.

This mini-review discusses the emerging role of the gut microbiome as an active driver of colorectal cancer initiation, progression, and therapeutic response. Key mechanisms include microbiome-induced genomic instability, modulation of host immune responses, and epigenetic reprogramming mediated by tumor-associated bacteria such as Fusobacterium nucleatum. Emerging evidence suggests that specific microbial signatures are not only associated with disease but can functionally shape tumor behavior, influence treatment sensitivity, and serve as clinically actionable biomarkers. These insights highlight the potential of integrating microbiome profiling into precision oncology and underscore the need for mechanistic and translational studies to harness host-microbe interactions for improved cancer prevention and therapy.

ABSTRACT Background Malignant pleural effusion (MPE) is associated with a poor prognosis and quality of life in patients with non‐small cell lung cancer (NSCLC). Additionally, cerebral edema can lead to neurological symptoms that adversely affect activities of daily living. While bevacizumab has demonstrated efficacy in treating both MPE and cerebral edema, there is limited research on ramucirumab, an angiogenesis inhibitor. Therefore, this study aimed to evaluate the efficacy of docetaxel combined with ramucirumab for the management of MPE and cerebral edema. Methods We retrospectively analyzed medical records of patients with advanced NSCLC who received docetaxel in conjunction with ramucirumab at Shizuoka Cancer Center between August 2016 and March 2023. The primary endpoints were pleural effusion progression‐free survival (PE‐PFS) and the cerebral edema control rate. Secondary endpoints included response rate, progression‐free survival (PFS), overall survival (OS), and the incidence of toxicities. Results A total of 163 patients were included. The median PE‐PFS was 8.1 months (95% CI: 4.8–12.0 months). The pleural effusion control rate was 87%, whereas the cerebral edema control rate was 26%. The response rate was 26%, with a median PFS of 4.4 months (95% confidence interval [CI]: 3.7–5.1 months) and a median OS of 11.1 months (95% CI: 9.2–16.0 months). Adverse events leading to discontinuation of treatment occurred in 30% of patients for docetaxel and 33% for ramucirumab, with fatigue being the most common reason for discontinuation. Conclusion Docetaxel plus ramucirumab was effective in controlling pleural effusion but showed limited effects on cerebral edema.

Colorectal cancer (CRC) is traditionally considered a "cold tumor" characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair-proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair-deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations-including RNA editing-act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy.

Objective:This study aimed to evaluate the feasibility and safety of combining touch care with aromatherapy in hospitalized patients with thoracic malignancies. Methods:Patients hospitalized in the thoracic oncology department at Shizuoka Cancer Center who had undergone chemotherapy, radiotherapy, or best supportive care were considered eligible for this prospective single-arm feasibility study. The intervention involved 20 minutes of touch care applied to the feet, following a manual from the Japan Sweden Care Institute, combined with aromatherapy, using a sachet of aroma beads soaked in essential oil placed on the chest of each patient throughout the session. The feasibility was assessed based on the proportion of patients completing the intervention. Safety was monitored by reporting adverse events, intervention-related discomfort, and abstention. Changes in subjective physical and emotional status before and after the intervention were assessed using questionnaires, while changes in physiological parameters were evaluated through heart rate variability frequency analysis and salivary stress hormone levels. Results:Among the 90 enrolled patients, 87 were evaluable and all completed the intervention. Regarding safety, intervention-related adverse event or discomfort was observed in 5 patients (5.7%), all of which were minor. Five of the six subjective physical and emotional status items significantly improved before and after the intervention. Physiological assessments showed an increase in parasympathetic nervous system activity, with significant reductions in salivary α-amylase and cortisol levels. No exacerbation of preexisting symptoms was observed. Conclusions:The combined intervention of touch care and aromatherapy was feasible and safe for hospitalized patients with thoracic malignancies undergoing cancer treatment.

e22585 Background: Epidermal Growth Factor Receptor (EGFR) mutation analysis in non-small cell lung cancer (NSCLC) is crucial for navigating treatment decision-making and improving survival outcomes. EGFR mutations are more prevalent among Asian Americans at 38.8% as compared to 17.4% in whites (REF). Hawaii has the highest proportion of Asian Americans and Native Hawaiian/Pacific Islanders (NH/PI) in the USA. Among this diverse population of Asian Americans, Native Hawaiians, and Pacific Islanders, the . Here, we present an analysis of EGFR-mutated NSCLC across diverse patient populations in Hawaii. Methods: This study included patients aged 18 years and older diagnosed with NSCLC at Hawaii Pacific Health between January 1, 2021, and December 31, 2023, and at Queen’s Medical Center between July 1, 2016, and December 31, 2022, in Hawaii (n = 281). Clinical data, including sex, race and ethnicity (whites, Filipino, Japanese American, other Asian American, NH/PI, and Other ethnicities), smoking status, and histological subtypes were also collected. Fisher’s exact test was used to analyze associations between EGFR mutations and patient characteristics. Results: Among 1028 NSCLC patients screened, 281 patients were appropriate for EGFR testing based on stage, histology, and clinical characteristics, of which 126 patients (44.8%) were positive. Female, Never-smokers, and adenocarcinoma histology were significantly associated with a higher prevalence of EGFR mutations (54.2%, 68.5%, and 54.3%, respectively; p < 0.05). As compared to whites, EGFR mutations were significantly more prevalent among Filipinos (OR 3.45; 95% CI: 1.52–8.10; p = 0.01), Japanese Americans (OR 2.42; 95% CI: 1.02–5.90; p = 0.03), and other Asian (OR 2.70; 95% CI: 1.13–6.68; p = 0.01). The prevalence of EGFR mutations among NH/PI was 42.3 %. No significant differences in EGFR mutation prevalence were observed among NH/PI patients with unknown/other races as compared to whites. Conclusions: To our knowledge, this is the first study to investigate the prevalence of EGFR mutations among various race and ethnic groups in Hawaii. Novel findings include: Filipino NSCLC cases having the highest prevalence of EGFR mutations and defining the prevalence of EGFR mutations in the NH/PI population (42.3%). Additional studies will explore the association between EGFR-mutant NSCLC and survival outcomes in this unique Hawaiian population.