Introduction: Although the efficacy of molecular targeted therapies varies across actionable genomic alterations in NSCLC, comparisons within a single real-world cohort remain limited. Methods: We conducted a retrospective multi-institutional study of 810 consecutive Japanese patients with advanced or recurrent NSCLC harboring actionable genomic alterations who received molecular targeted therapy from 2017 to 2023. Patients were classified into the following three genomic groups: EGFR mutations (group A), ALK/ROS1/RET fusion oncogenes (group B), and others, including MET exon 14 skipping, BRAF V600E, and KRAS G12C mutations (group C). Treatment efficacy and safety were compared across the groups. Results: Treatment outcomes differed between the subgroups. Group B demonstrated the highest objective response rate (85.8%) and the longest median real-world progression-free survival (rwPFS; 42.5 mo); median overall survival (OS) was not reached. Group A had intermediate outcomes. Group C exhibited the shortest rwPFS (9.2 mo), poorer OS, and higher rates of treatment discontinuation due to adverse events. Such hierarchical differences were observed in patients with baseline central nervous system metastases and in those receiving first-line treatment. In multivariate analysis, genomic subgroup remained associated with rwPFS and OS, with fusion-driven tumors maintaining superior outcomes irrespective of other factors. Conclusions: This large real-world analysis yielded a hierarchy of therapeutic benefits across actionable genomic alterations in NSCLC. Patients with fusion-driven tumors benefited from targeted therapy, whereas those with EGFR-mutated tumors had intermediate outcomes. Treatment of patients with MET exon 14 skipping, BRAF V600E, and KRAS G12C mutations had limited efficacy and higher toxicity, underscoring the need for improved therapeutic strategies.

Background:The combination of an anti-programmed death-ligand 1 (PD-L1) antibody with etoposide and either carboplatin or cisplatin (platinum-etoposide) has become the first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). Although previous studies have examined the relationship between geriatric assessments and treatment efficacy, the association with treatment tolerability in elderly patients with ES-SCLC remains insufficiently understood. We aimed to evaluate the association between low body mass index (BMI)-a component of geriatric assessment-and treatment tolerability. Methods:We conducted a retrospective analysis of patients aged ≥65 years with ES-SCLC who received anti-PD-L1 antibody plus platinum-etoposide at a single center between August 2019 and April 2024. Tolerability was defined as the completion of four cycles of anti-PD-L1 antibody combined with platinum-etoposide. We also assessed treatment efficacy and safety profiles. Results:A total of 71 patients were included, with a median age of 73 years (range: 65-91 years). Of these, 51 patients (72%) were male, and 54 (76%) had an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1. Sixteen patients (23%) showed a low BMI (<19 kg/m2), whereas 55 (77%) showed a non-low BMI. Tolerability was achieved in 8 patients (50%) with low BMI compared with 44 patients (80%) with non-low BMI. There were no significant differences in overall survival, progression-free survival, or the incidence of grade ≥3 adverse events among the two groups. In multivariate analysis, low BMI and ECOG-PS ≥2 were independently associated with reduced treatment tolerability [odds ratio (OR): 0.24, 95% confidence interval (CI): 0.06-0.88, P=0.03; OR: 0.13, 95% CI: 0.04-0.48, P<0.01, respectively]. Conclusions:Low BMI and poor performance status were independently associated with decreased tolerability to anti-PD-L1 antibody combined with platinum-etoposide in elderly patients with ES-SCLC. These findings underscore the importance of incorporating geriatric assessments into treatment decision-making for this population.

8559 Background: Pembrolizumab plus platinum-based chemotherapy is a standard first-line treatment for previously untreated advanced squamous non-small cell lung cancer (NSCLC) based on the KEYNOTE-407 trial. Ubenimex, an oral CD13/aminopeptidase inhibitor, has immunostimulatory and antitumor activity. We conducted a phase II trial to assess the safety and efficacy of ubenimex in combination with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. Methods: This study was a prospective, multicenter, single-arm phase II trial. Eligible patients with previously untreated advanced squamous NSCLC received ubenimex orally plus 4 cycles of pembrolizumab, nab-paclitaxel, and carboplatin, followed by continuous administration of ubenimex and pembrolizumab for a maximum of 2 years. To confirm tolerability, the daily dose of ubenimex started at level 1 (30mg/day), which was increased to levels 2 (60 mg/day) and 3 (120 mg/day) according to the escalation criteria, with a standard 3 + 3 design for achieving the target dose-limiting toxicity (DLT) rate of 33%. The efficacy, safety, and tolerability of ubenimex at the determined dose level were analyzed. The primary efficacy endpoint was objective response rate (ORR) by independent central review, estimated descriptively with a 90% confidence interval; the ORR in the KEYNOTE-407 (62.6%) served as a reference value for study design. Results: No DLTs were observed across dose levels 1–3. Therefore, level 3 was selected as the recommended dose. From January 2024 to January 2025, 28 patients were enrolled from 18 institutions, and all patients were evaluable for efficacy and safety. Baseline characteristics were male/female 25/3; median age 72 (range, 40-86); ECOG PS 0/1 12/16. The ORR was 71.4% (90% CI, 54.3-84.9). With a median follow-up of 12.8 months, median progression-free survival (PFS) was 16.8 months (95% CI, 5.6-not reached); median overall survival (OS) was not reached. Grade 3/4 adverse events included pneumonitis (3.6%), anemia (46.4%), febrile neutropenia (10.7%). There was no treatment-related death. Conclusions: Ubenimex with 120 mg/day (60 mg twice daily) combined with pembrolizumab, nab-paclitaxel, and carboplatin was feasible and showed encouraging antitumor activity with manageable safety in previously untreated advanced squamous NSCLC, supporting further randomized evaluation. Clinical trial information: jRCT2031210707.

Background:Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and an independent determinant of prognosis. Increases in pulmonary vascular resistance often precede overt elevation of pulmonary arterial pressure, but early pulmonary vascular involvement remains difficult to detect noninvasively. Conventional echocardiographic assessment in COPD focuses mainly on right ventricular systolic indices, which may remain preserved despite increased pulmonary vascular load. Methods:We conducted a single-center retrospective observational study of 58 patients with stable COPD who underwent right heart catheterization and comprehensive transthoracic echocardiography during the same hospitalization. Right ventricular isovolumetric relaxation time (IRT), a Doppler-derived index of diastolic timing, was evaluated in relation to invasively measured pulmonary vascular resistance, dyspnea severity, exercise capacity, and pulmonary function. Results:A total of 58 patients were included. Patients meeting hemodynamic criteria for pulmonary hypertension exhibited lower diffusing capacity, more severe dyspnea, and reduced exercise capacity despite similar airflow limitation. Pulmonary vascular resistance was significantly higher, while cardiac index remained preserved. IRT was significantly prolonged in patients with pulmonary hypertension and showed a moderate correlation with pulmonary vascular resistance (ρ = 0.56, p < 0.001), six-minute walk distance (ρ = -0.46, p < 0.001), and dyspnea severity (ρ = 0.36, p = 0.006). In contrast, conventional right ventricular systolic indices showed no significant associations with pulmonary vascular resistance. Conclusion:Echocardiographic assessment of IRT may provide a physiologically grounded, noninvasive parameter associated with early right ventricular diastolic response to pulmonary vascular load.

Background:Previous studies have reported an association between expression of thyroid transcription factor 1 (TTF-1) and the efficacy of immune checkpoint inhibitors (ICIs), cytotoxic chemotherapy, and immunochemotherapy in patients with advanced non-squamous non-small cell lung cancer (NS-NSCLC). However, the relationship between TTF-1 expression and the efficacy of cytotoxic chemotherapy in patients with NS-NSCLC with idiopathic interstitial pneumonias (IIPs) remains unclear. This study aimed to evaluate the relationship TTF-1 expression and the efficacy of platinum-doublet chemotherapy in patients with NS-NSCLC with coexisting IIPs. Methods:This retrospective study reviewed 120 patients with NSCLC complicated by IIPs who were treated at Nippon Medical School Hospital in Japan between January 2010 and December 2024. We analyzed the efficacy and safety of carboplatin and either paclitaxel or nanoparticle albumin-bound (nab-) paclitaxel for NS-NSCLC with IIPs. Results:In the total cohort, 51 patients were evaluated for TTF-1 expression status and administered carboplatin plus (nab-) paclitaxel as first-line therapy. TTF-1 expression was observed in 32 patients (63%). Twenty-five patients (49%) exhibited a usual interstitial pneumonia (UIP) pattern. The overall response rate (ORR) was significantly higher in the TTF-1-positive group compared to the TTF-1-negative group (62.4% vs. 31.6%, P=0.045). Median overall survival (OS) and progression-free survival (PFS) were also significantly longer in the TTF-1-positive group than in TTF-1-negative group (11.3 vs. 8.2 months, P=0.007; 8.4 vs. 4.4 months, P<0.001). TTF-1 negativity was identified as an independent prognostic factor associated with inferior OS and PFS in multivariate analysis. Furthermore, the TTF-1-negative group had a significantly higher incidence of lung cancer development in the setting of underlying interstitial pneumonia (IP) (P<0.001), suggesting that decreased TTF-1 expression may be involved in the pathogenesis of lung cancer arising from IIPs. Conclusions:TTF-1 expression is an independent prognostic factor in patients with NS-NSCLC complicated by IIPs who received carboplatin plus (nab-) paclitaxel. TTF-1 expression may represent a valuable biomarker for characterizing the disease subtypes and guiding therapeutic strategies in lung cancer with coexisting IIPs.

BACKGROUND:Non-invasive methods for detailed evaluation of airway pathology in asthma, including structural airway abnormalities, remain limited, and accurate assessment is still insufficient. The MostGraph, which utilizes the impulse oscillation system (IOS), allows non-invasive measurement of airway resistance and reactance. This study evaluated its utility in distinguishing airway pathology between bronchial asthma (BA) and cough variant asthma (CVA), with a focus on peripheral airway involvement. METHODS:In this cross-sectional study, 383 patients with stable respiratory symptoms for over three months were enrolled (203 BA, 180 CVA). All patients underwent spirometry, IOS assessment using the MostGraph, blood tests, and fractional exhaled nitric oxide (FeNO) measurement. RESULTS:Body composition was comparable between groups, although BA patients were older. BA showed significantly greater airway obstruction (%FEV1/predicted FEV1) and peripheral impairment (V50/V25, MMF). R5-R20 values were higher in BA than CVA before and after bronchodilator use. In BA, R5, R20, and R5-R20 correlated significantly with %FEV1; in CVA, only R5 and R20 did. R5-R20 showed no correlation (R = -0.11, P = 0.14). Inspiratory R5-R20 was not correlated in CVA (Pre-BD: R = -0.048, P = 0.53; Post-BD: R = -0.13, P = 0.091), while all parameters correlated in BA. Fres was significantly higher in BA both pre- and post-bronchodilator (P < 0.0001). CONCLUSION:MostGraph indices, when integrated with spirometry, may offer a valuable non-invasive approach for characterizing peripheral airway abnormalities that may reflect remodeling-related changes in BA and support airway monitoring in asthma management. TRIAL REGISTRATION:UMIN-CTR Clinical Trial (UMIN000054006). (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000061647).

BACKGROUND:Pulmonary hypertension (PH) complicates chronic obstructive pulmonary disease (COPD) and is associated with adverse outcomes. However, the clinical relevance of pulmonary vascular resistance (PVR) in non-hypoxemic COPD patients without severe PH remains unclear. METHODS:This pre-specified secondary analysis of a prospectively registered cohort (UMIN000042159) included non-hypoxemic COPD patients who underwent right heart catheterization and were managed without PH-targeted therapy. Patients were classified as having preliminary pulmonary vascular abnormality (resting mean pulmonary artery pressure [mPAP] ≤ 20 mmHg with exercise-related elevation during a study-specific exercise protocol) or mild-to-moderate PH (20 < resting mPAP <35 mmHg). The primary outcome was two-year overall survival. Secondary outcomes included home-stay survival and functional capacity assessed by 6-min walk distance (6MWD), metabolic equivalents (MET), and modified Medical Research Council (mMRC) dyspnea score. RESULTS:Thirty-seven patients were analyzed. During follow-up, 18 patients lost independent living and 11 died. Higher PVR and mPAP were associated with reduced home-stay survival and overall survival. PVR demonstrated the strongest association with mortality (hazard ratio 1.45, p = 0.0007). PVR was correlated with mMRC (ρ = 0.65), 6MWD (ρ = -0.62), and MET (ρ = -0.49). Spirometric indices were not predictive of survival. CONCLUSIONS:In non-hypoxemic COPD patients without severe PH, pulmonary vascular resistance was associated with functional limitation and two-year prognosis. suggesting that pulmonary vascular burden is an important determinant of near-term outcomes. CLINICAL TRIAL REGISTRATION:UMIN-CTR (UMIN000042159).

Background:Managing malignant pleural effusion (MPE) with pleurodesis is essential for symptom relief and minimizing the need for repeated thoracentesis. Interstitial lung disease (ILD) is one of the most common complications associated with advanced lung cancer. However, the efficacy and safety of pleurodesis for MPE secondary to lung cancer with ILD remains unclear. This study aimed to evaluate the efficacy and safety of pleurodesis in this population. Methods:This study was a single-center retrospective analysis. The cases of pleurodesis in patients with MPE secondary to lung cancer complicated with ILD at Nippon Medical School Hospital (Tokyo, Japan) between January 2010 and December 2022 were included. Results:Of the 26 lung cancer patients with ILD who underwent pleurodesis were analyzed. Fourteen patients received talc and 12 patients received minocycline, respectively. Talc was used in 10 out of 14 patients with drug-induced ILD and radiation-induced lung injury (RILI). In contrast, minocycline was used in 10 out of 12 patients with idiopathic interstitial pneumonias (IIPs). One month after pleurodesis, the efficacy for pleural adhesions was 64.3% and 50.0% in the talc and minocycline groups. The presence of a partially expanded lung before pleurodesis was a predictive factor for failure [odds ratio: 7.00, 95% confidence interval (CI): 1.20-40.83, P=0.04]. When excluding the patients presenting partially expanded lung, the efficacy rate was 77.8% and 71.4% in the talc and minocycline groups. One case of grade 5 acute respiratory distress syndrome (ARDS) was observed in each group. All cases developing ARDS had been treated with systemic prednisolone against ILDs presenting ground glass opacity and consolidation within 6 months before pleurodesis. Conclusions:Pleurodesis is considered to be one of the treatment options against MPE in patients with ILD. However, two cases of ARDS were observed; thus, clinicians should carefully consider the indication of pleurodesis in the patients who had the recent onset of ILD and were treated with systemic prednisolone.

Acute exacerbation (AEx) of interstitial pneumonia is the most common lethal adverse event related to the pharmacological treatment of patients with lung cancer complicated with interstitial pneumonia. Although small cell lung cancer (SCLC) is linked to poor prognosis, it exhibits good response to chemotherapy. Few previous research studies have investigated the safety and efficacy of treatment for advanced SCLC complicated with idiopathic interstitial pneumonia (IIP). We conducted a single-arm phase II study to evaluate the safety and efficacy of carboplatin plus etoposide for the treatment of patients with SCLC complicated with IIP. Chemotherapy-naïve patients with advanced SCLC complicated with IIP were enrolled. Patients received carboplatin every 21–28 days at a dose of area under the curve 4–6 on day 1 and etoposide at a dose of 80–100 mg/m2 on days 1–3. Thirty-one patients were enrolled between December 2009 and December 2022. A median of four cycles of carboplatin plus etoposide were administered. Acute exacerbation of idiopathic interstitial pneumonia was not observed; the rate of AEx was 0

Recently, immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of small cell lung cancer (SCLC). While their development has enhanced treatment options for SCLC, the effectiveness of immunotherapy remains limited due to the low expression of Programmed Cell Death Ligand 1 (PD-L1) and the emergence of immunotherapy resistance. As a result, there is a pressing need for new biomarkers to guide SCLC treatment. We obtained four microarray datasets from GEO (Gene Expression Omnibus) database and screened differentially expressed genes (DEGs). After the establishment of protein-protein interaction network through Cytoscape, key hub genes were selected via a volcano plot. To validate these results, we used an independent dataset as a test cohort. We also analyzed differences in immune cell infiltration between normal and SCLC samples. Lastly, we identified a marker gene associated with immune cell infiltration and validated its role in SCLC through in vitro experiments. We screened GEO gene expression database for DEGs, which are immune-related genes, in SCLC. A PPI network analysis revealed seven overexpressed hub genes (AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, AURKA) in the SCLC cohort, which were significantly more expressed than in normal cells. Correlation analysis between immune cells and the seven hub genes showed that BIRC5 expression was inversely correlated with monocytes. In SCLC cell lines such as SBC5 and SBC3, downregulation of BIRC5 using siRNA induced apoptosis and inhibited cell activity, tumor invasiveness and proliferative potential. Furthermore, treatment with a BIRC5 inhibitor (YM155) reduced SCLC cell viability and increased apoptosis. Co-culture experiments with SBC3 and monocytes (e.g., THP1) led to decreased BIRC5 expression in SBC3 cells. We identified AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, and AURKA genes as potential immune-related therapeutic targets for SCLC. In particular, high BIRC5 expression promotes SCLC progression and may influence the immune microenvironment of the tumor by affecting monocytes. Akihiko Miyanaga, Yang Yunchu, Kuniko Matsuda, Takehiro Tozuka, Aya Fukuizumi, Kakeru Hisakane, Naomi Onda, Susumu Takeuchi, Koichiro Kamio, Kazuo Kasahara, Masahiro Seike. Immune-associated genes as potential therapeutic targets in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5687.

Background/Aim: Chemoresistance to paclitaxel (PTX) significantly ameliorates therapeutic efficacy in patients with non-small cell lung cancer (NSCLC), especially in advanced stages, deteriorating the progression free and overall survival rates. One of the critical mechanisms contributing to drug resistance is the excretion of PTX from target cells via efflux pumps. Ivermectin was developed as a bactericidal agent against parasites; however, it has recently been shown to inhibit the proliferation of human cancer cells. Hence, we aimed to evaluate the therapeutic potential of ivermectin in combination with PTX and investigate the molecular mechanisms by which ivermectin overcomes PTX resistance. Materials and Methods: We assessed the antitumor effects of ivermectin in A549 cells treated with or without PTX. We also established PTX-resistant cells using this cell line and explored the underlying mechanisms. Additionally, we evaluated whether ivermectin attenuates PTX-resistance with the retrieval of drug sensitivity. Results: Combined treatment of A549 cells with PTX and ivermectin inhibited cell growth. These cells acquired chemoresistance upon long-term exposure to gradually increasing PTX concentrations, which was accompanied by ABCB1 mRNA up-regulation, and subsequent overproduction of P-glycoprotein (P-gp). Consistent with this, P-gp overexpression resulted in a PTX-resistant phenotype. Notably, the simultaneous ivermectin treatment during the gradual exposure completely abolished P-gp expression, leading to an increased intracellular PTX concentration and sustained PTX sensitivity. Ivermectin was found to regulate P-gp expression via the EGFR/ERK/Akt/NF-& kgreen;B pathway. Conclusion: Combined highlighting a novel therapeutic avenue for drug repurposing.

AbstractIntroductionA neurotrophic tropomyosin receptor kinase (NTRK)‐tyrosine kinase inhibitor (TKI) has shown dramatic efficacy against malignant tumors harboring an NTRK fusion gene. However, almost all tumors eventually acquire resistance to NTRK‐TKIs.MethodTo investigate the mechanism of resistance to NTRK‐TKIs, we established cells resistant to three types of NTRK‐TKIs (larotrectinib, entrectinib, and selitrectinib) using KM12 colon cancer cells with a TPM3‐NTRK1 rearrangement.ResultOverexpression of 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (HMGCS2) was observed in three resistant cells (KM12‐LR, KM12‐ER, and KM12‐SR) by microarray analysis. Lower expression of sterol regulatory element‐binding protein 2 (SREBP2) and peroxisome proliferator activated receptor α (PPARα) was found in two cells (KM12‐ER and KM12‐SR) in which HMGCS2 was overexpressed compared to the parental KM12 and KM12‐LR cells. In resistant cells, knockdown of HMGCS2 using small interfering RNA improved the sensitivity to NTRK‐TKI. Further treatment with mevalonolactone after HMGCS2 knockdown reintroduced the NTRK‐TKI resistance. In addition, simvastatin and silibinin had a synergistic effect with NTRK‐TKIs in resistant cells, and delayed tolerance was observed after sustained exposure to clinical concentrations of NTRK‐TKI and simvastatin in KM12 cells. In xenograft mouse models, combination treatment with entrectinib and simvastatin reduced resistant tumor growth compared with entrectinib alone.ConclusionThese results suggest that HMGCS2 overexpression induces resistance to NTRK‐TKIs via the mevalonate pathway in colon cancer cells. Statin inhibition of the mevalonate pathway may be useful for overcoming this mechanistic resistance.

A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors.

Introduction: Osimertinib is a standard treatment for patients with EGFR -mutant NSCLC. Although some osimertinib resistance mechanisms have been identi fied, nearly 50% of the mechanisms remain to be elucidated. This study was aimed at identifying non -genetic mechanisms underlying osimertinib resistance. Methods: We established two osimertinib-resistant cell lines from EGFR mutation -positive PC -9 and HCC827 NSCLC cell lines (PC-9OR and HCC827OR, respectively) using a stepwise method. We compared the phosphoproteomic pro files of the osimertinib-resistant and parental cells using mass spectrometry. Upstream kinases were identi fied using the application Kinase Enrichment Analysis version 3. Results: Phosphoproteomic analysis revealed 80 phosphorylation sites that were mutually up -regulated in PC9OR and HCC827OR cells. The Kinase Enrichment Analysis version 3 analysis identi fied focal adhesion kinase (FAK) and proto-oncogene tyrosine -protein kinase Src (Src) as upstream kinases of these up -regulated phosphoproteins. The small -interfering RNA -mediated knockdown of FAK reduced Src phosphorylation and that of Src reduced FAK phosphorylation in both cell lines. Furthermore, FAK- or Src-speci fic small -interfering RNA treatments restored EGFR phosphorylation in PC-9OR and HCC827OR cells. The combination of FAK and Src inhibitors inhibited PC-9OR and HCC827OR cell proliferation in vitro and suppressed tumor growth in a xenograft mouse model. Immunohistochemistry of tumors from patients with EGFR -mutant NSCLC suggested that phosphorylated FAK and Src are involved in initial and acquired resistance to osimertinib. Conclusions: Phosphoproteomic analysis may help elucidate the mechanisms of resistance to molecular -targeted therapies in lung cancer. Mutual phosphorylation of FAK and Src is involved in osimertinib resistance. Thus, FAK and Src inhibition may be novel treatment strategies for osimertinib-resistant NSCLC. Copyright (c) 2024 by the International Association for the Study of Lung Cancer. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

BACKGROUND:In recent years, as the availability of precision therapies expands, there is increasing reliance on genomic profiling assays to help identify the most appropriate treatment options for patients with advanced cancers. We retrospectively investigated the results of comprehensive genomic profiling tests from the time insurance coverage began until recently and examined the status of genetic analysis. METHODS:We retrospectively reviewed the analysis results of 300 patients with advanced solid tumors who consented to comprehensive genomic profiling tests from October 2019 to December 2022. RESULTS:Of the 300 patients who underwent comprehensive genomic profiling tests, analysis results for 274 patients were obtained, and were reviewed by the Clinical Genome Expert Panel. Six specimens (2%) were discontinued due to patient deaths and deteriorations in general condition. The three most frequently occurring actionable genomic alterations observed were TP53 (47.4%), KRAS (28.1%) and CDKN2A (20.4%). The most common druggable variant was CDKN2A, which was noted in 52 (19%) of 274 patients. The next most common were PIK3CA, BRAF, KRAS and PTEN. The cancer types that showed a greater median number of actionable alterations comprised thyroid cancer, pancreatic cancer and colorectal cancer. CONCLUSIONS:In conclusion, comprehensive genomic profiling tests have the potential to be valuable in identifying genomic abnormalities. Even if there is no effective treatment at present, it may lead to a treatment in the future. Comprehensive genomic profiling tests should be considered for any cancer.