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BACKGROUND: The treatment of lung cancer has made dramatic progress in the past decade, but due to the high cost of drugs, the total pharmaceutical cost has been rising explosively. There are currently no data available in Japan on which regimens are used, to what extent they are used, and what their total cost is. METHODS: Sixty Japanese centers belonging to the Lung Cancer Study Group of the Japan Clinical Oncology Group were surveyed for information about the first-line treatment for advanced lung cancer in practice from July 2021 to June 2022. Three types of cancer were included: driver gene mutation-negative NSCLC, EGFR mutation-positive NSCLC, and extensive-stage small cell lung cancer (ES-SCLC). RESULTS: Recent treatment costs for ICIs or ICI plus chemotherapy were about 20-55 times higher than those for conventional chemotherapy. Of the 3738 patients with driver gene aberration-negative NSCLC, 2573 (68.8%) received treatments with monthly cost of 500 000 Japanese yen (JPY) or more; 2555 (68.4%) received ICI therapy. Of the 1486 patients with EGFR mutation-positive NSCLC, 1290 (86.8%) received treatments with a monthly cost of 500 000 JPY or more; 1207 (81.2%) received osimertinib. ICI treatments with a monthly cost of 500 000 JPY or more were administered to 607 (56.3%) of 1079 patients with ES-SCLC. Elderly NSCLC patients received slightly more high-cost treatment than younger patients. CONCLUSION: Recent treatments cost many times more than conventional chemotherapy. This study revealed that high-cost treatments were widely used in advanced lung cancer and some of high-cost treatments were used despite the lack of clear evidence. Physicians should pay attention to the cost of treatments they use.
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BACKGROUND: Chemotherapy-induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy-induced anorexia and weight loss during platinum-based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy-induced anorexia and therapeutic outcomes in patients with stage IV non-small-cell lung cancer undergoing platinum-based chemotherapy combined with immune checkpoint inhibitors. METHODS: The study retrospectively reviewed the medical records of 106 patients with stage IV non-small-cell lung cancer treated with platinum-based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy-induced anorexia group. Chemotherapy-induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression-free and overall survival were used to measure treatment efficacy. RESULTS: Chemotherapy-induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non-chemotherapy-induced anorexia group. Progression-free and overall survival were shorter in the chemotherapy-induced anorexia group than in the non-chemotherapy-induced anorexia group, but the difference was not statistically significant. CONCLUSIONS: Chemotherapy-induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non-small-cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy-induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum-based chemotherapy combined with immune checkpoint inhibitors.
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Anorexia , Neoplasias Pulmonares , Humanos , Anorexia/induzido quimicamente , Anorexia/etiologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Resultado do TratamentoRESUMO
INTRODUCTION: The effect of polypharmacy on older patients with cancer is unclear. This study aimed to explore the effect of polypharmacy on the outcomes of treatment in older patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. MATERIALS AND METHODS: We retrospectively reviewed the records of older patients (aged ≥65 years) with advanced NSCLC who received PD-1/PD-L1 inhibitors with or without platinum-based chemotherapy as first-line treatment from March 2016 to December 2020. Patients with driver oncogenes or Eastern Cooperative Oncology Group performance status (PS) ≥2 were excluded. Polypharmacy was defined as receiving five or more oral or inhaled medications at baseline. We compared the progression-free survival (PFS), overall survival (OS), and mean cumulative length of hospital stays between the polypharmacy and non-polypharmacy groups. RESULTS: A total of 122 patients, with a median age of 72 years (range, 65-89 years), were included in the analysis. Of the patients, 34 (27.8%) had a PS of 0 and 68 (55.7%) had a PD-L1 tumor proportion score (TPS) of ≥50%. The median number of oral or inhaled medications was 4 (range, 0-12), and 60 (49.1%) patients were taking ≥5 medications (polypharmacy). Age and Charlson Comorbidity Index score were significantly higher in the polypharmacy group (P = 0.01 and P < 0.001, respectively). Compared with the non-polypharmacy group, the polypharmacy group had a similar median PFS (6.7 vs. 8.5 months, P = 0.94) and a shorter median OS (17.3 vs. 26.0 months, P = 0.04). In the polypharmacy group, the adjusted hazard ratio for OS (adjusted for age, PS, and PD-L1 TPS) was 1.65 (95% confidence interval, 1.04-2.86, P = 0.03). Patients in the polypharmacy group had longer hospital stays (46.3 ± 7.5 vs. 27.7 ± 4.1 days/person, P < 0.05) and more emergency hospitalizations (1.6 ± 0.3 vs. 0.8 ± 0.1 times/person, P < 0.05) during the first year. DISCUSSION: Polypharmacy was associated with shorter survival time and longer hospitalization in older patients with advanced NSCLC receiving first-line immunotherapy with or without chemotherapy.
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BACKGROUND: The AmoyDx Pan lung cancer PCR panel (AmoyDx PLC panel) has been approved as a companion diagnostic tool for multiple anticancer agents in patients with non-small cell lung cancer (NSCLC). However, the suitability of cytology specimens as samples for the AmoyDx PLC panel remains unclear. We evaluated the performance of frozen cell pellets from cytology specimens (FCPs) in the Amoy 9-in-1 assay, a preapproval assay of the AmoyDx PLC panel. METHODS: We retrospectively collected data of NSCLC patients enrolled in LC-SCRUM-Asia from the Shizuoka Cancer Center between September 2019 and May 2021. RESULTS: A total of 49 cases submitted FCPs for evaluation of oncogenic driver alterations and were assessed using Amoy 9-in-1 and next-generation sequencing (NGS) assays. The success rates of DNA and RNA analyses using the Amoy 9-in-1 were both 100%, compared with 86% and 45%, respectively, using NGS assays. Oncogenic driver alterations were detected in 27 (55%) and 23 (47%) patients using Amoy 9-in-1 and NGS, respectively. No inconsistent results were observed among 19 cases in which both assays showed successful detection. In the remaining 30 cases, 10 had inconsistent results: nine oncogenic driver alterations (3 MET, 2 ALK, 2 ROS1, and 2 KRAS) were detectable only in Amoy 9-in-1, and one epidermal growth factor receptor (EGFR) mutation was detectable only in NGS. CONCLUSION: FCPs can be successfully used in the AmoyDx PLC panel, with higher success rate compared with the NGS assay. The AmoyDx PLC panel may be an option in cases when insufficient tissue sample is available for the NGS assay.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Estudos Retrospectivos , Técnicas CitológicasRESUMO
BACKGROUND: To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non-small cell lung cancer (NSCLC) in real-world settings. METHODS: We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first-line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow-up data were obtained using medical records from diagnosis to March 1, 2018. RESULTS: Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3-year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3-year progression-free survival (PFS) and disease-free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29-0.81]), PFS (0.62 [0.39-0.96]), and DFS (0.62 [0.39-0.97]) versus surgery alone. CONCLUSIONS: Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estadiamento de Neoplasias , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Masculino , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Idoso , Pessoa de Meia-Idade , Japão , Resultado do Tratamento , Idoso de 80 Anos ou mais , Pneumonectomia/métodos , Estudos de Coortes , Adulto , População do Leste AsiáticoRESUMO
BACKGROUND: Anamorelin is a selective ghrelin receptor agonist approved for cancer cachexia in Japan. Little is known about predictors of anamorelin efficacy. This study aimed to assess the effect of diabetes on the efficacy and safety of anamorelin in patients with cancer cachexia. METHODS: Medical records of patients with advanced non-small-cell lung, gastric, pancreatic, or colorectal cancer who received anamorelin between January 2021 and March 2023 were retrospectively reviewed. The diabetic (DM) group included patients with a confirmed diagnosis of type 2 diabetes mellitus, random plasma glucose of ≥ 200 mg/dL, or hemoglobin A1c of ≥ 6.5%. The maximum body weight gain and adverse events during anamorelin administration were compared between the DM and non-DM groups. Patients with a maximum body weight gain ≥ 0 kg were classified as the responders. RESULTS: Of 103 eligible patients, 31 (30.1%) were assigned to the DM group. The DM group gained less weight (median of -0.53% vs. + 3.00%, p < 0.01) and had fewer responders (45.2% vs. 81.9%, p < 0.01) than the non-DM group. The odds ratio for non-response in the DM group was 6.55 (95% confidential interval 2.37-18.06, p < 0.01), adjusted by age and performance status. The DM group had a higher cumulative incidence of hyperglycaemic adverse events (72.2% vs. 6.3%, p < 0.01) and more discontinuations due to hyperglycaemic adverse events (25.8% vs. 4.2%, p < 0.01) than the non-DM group. CONCLUSIONS: Patients with diabetes and cancer cachexia are less likely to gain weight with anamorelin despite a high risk of hyperglycaemic adverse events.
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Caquexia , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Caquexia/tratamento farmacológico , Caquexia/etiologia , Oligopeptídeos/uso terapêutico , Oligopeptídeos/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Idoso de 80 Anos ou mais , Hemoglobinas Glicadas/análise , Glicemia/análise , Aumento de Peso/efeitos dos fármacos , Receptores de Grelina/agonistas , Resultado do Tratamento , HidrazinasRESUMO
BACKGROUND: MET exon 14 skipping mutations occur in 3-4% and MET high amplifications occur in < 1% of patients with non-small-cell lung cancer (NSCLC). Crizotinib, a selective ATP-competitive small-molecule inhibitor of c-Met, ALK, and ROS1 tyrosine kinases, has shown activity in cancer models with various types of MET activation. METHODS: The Co-MET study is a single-arm phase 2 trial to assess the safety and efficacy of crizotinib in MET inhibitor-naïve patients with advanced NSCLC harboring MET exon 14 skipping mutation (cohort 1) or high MET gene copy number of ≥ 7 (cohort 2). The primary endpoint was the objective response rate (ORR) per RECIST v1.1 by independent radiology review in cohort 1. The key secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 28 patients (23 in cohort 1 and 5 in cohort 2) were enrolled between March 2018 and February 2020. The primary endpoint was met as the ORR (90% confidence interval: CI) in cohort 1 was 38.1% (20.6-58.3). Median DoR, PFS, and OS (95% CI) were 7.6 (1.9-NE), 5.7 (2.1-11.3), 9.1 (4.0-19.9) months, respectively, in cohort 1. ORR in cohort 2 was 40.0% (18.9-92.4). The safety signals were generally consistent with the known safety profile of crizotinib. CONCLUSIONS: Crizotinib showed a clinical activity similar to that of tepotinib and capmatinib in patients with NSCLC harboring MET exon 14 skipping mutations. CLINICAL TRIAL INFORMATION: UMIN000031623.
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Carcinoma Pulmonar de Células não Pequenas , Crizotinibe , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas c-met , Humanos , Crizotinibe/uso terapêutico , Proteínas Proto-Oncogênicas c-met/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Idoso , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Japão , Intervalo Livre de Progressão , Éxons , População do Leste AsiáticoRESUMO
OBJECTIVES: The main objective of this report was to detail the long-term follow-up data from the REMORA study, which investigated the safety and efficacy of lenvatinib in patients with thymic carcinoma. In addition, an exploratory analysis of the association between relative dose intensity (RDI) and the efficacy of lenvatinib is presented. MATERIALS AND METHODS: The single-arm, open-label, phase 2 REMORA study was conducted at eight Japanese institutions. Forty-two patients received oral lenvatinib 24 mg once daily in 4-week cycles until the occurrence of intolerable adverse events or disease progression. The REMORA long-term follow-up data were evaluated, including overall survival (OS). RDI was calculated by dividing the actual dose administered to the patient by the standard recommended dose. This trial is registered on JMACCT (JMA-IIA00285) and on UMIN-CTR (UMIN000026777). RESULTS: The updated median OS was 28.3 months (95 % confidence interval [CI]: 17.1-34.0 months), and the OS rate at 36 months was 35.7 % (95 % CI: 21.7 %-49.9 %). When grouped by RDI of lenvatinib, the median OS was 38.5 months (95 % CI: 31.2-not estimable) in patients with ≥ 75 % RDI and 17.3 months (95 % CI: 13.4-26.2 months) in patients with < 75 % RDI (hazard ratio 0.46 [95 % CI: 0.22-0.98]; P = 0.0406) at 8 weeks. Patients who maintained their lenvatinib dose over 8 weeks had a higher objective response rate than patients whose doses were reduced (75.0 % vs 29.4 %; P = 0.0379). No new safety concerns or treatment-related deaths were reported, and lenvatinib had a tolerable safety profile. CONCLUSION: This follow-up report updated OS in patients with metastatic or recurrent thymic carcinoma. A higher RDI of lenvatinib at 8 weeks could be associated with improved outcomes.
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Recidiva Local de Neoplasia , Compostos de Fenilureia , Quinolinas , Timoma , Humanos , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Seguimentos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Timoma/tratamento farmacológico , Timoma/mortalidade , Timoma/patologia , Adulto , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/patologia , Neoplasias do Timo/mortalidade , Metástase Neoplásica , Idoso de 80 Anos ou mais , Resultado do TratamentoRESUMO
The efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) is unclear. This study aimed to evaluate the efficacy of second-line chemotherapy in patients with pulmonary LCNEC. We retrospectively reviewed patients with pulmonary LCNEC or possible LCNEC (pLCNEC) who received platinum-based chemotherapy as the first-line treatment. Among these patients, we evaluated the efficacy of second-line treatment by comparing patients with small cell lung cancer (SCLC group). Of the 61 patients with LCNEC or pLCNEC (LCNEC group) who received first-line chemotherapy, 39 patients were treated with second-line chemotherapy. Among the 39 patients, 61.5% received amrubicin monotherapy. The median progression-free survival (PFS) and overall survival (OS) in the LCNEC groups were 3.3 and 8.3 months, respectively. No significant differences in the PFS (hazard ratio [HR]: 0.924, 95% confidence interval [CI] 0.647-1.320; P = 0.664) and OS (HR: 0.926; 95% CI 0.648-1.321; P = 0.670) were observed between the LCNEC and SCLC groups. In patients treated with amrubicin, the PFS (P = 0.964) and OS (P = 0.544) were not different between both the groups. Second-line chemotherapy, including amrubicin, may be considered as a treatment option for patients with pulmonary LCNEC.
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Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Antraciclinas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/patologiaRESUMO
BACKGROUND: DESTINY-Lung01 is a multicentre, open-label, phase 2 study evaluating the antitumour activity and safety of trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate, in patients with HER2-overexpressing or HER2 (ERBB2)-mutant unresectable or metastatic non-small-cell lung cancer (NSCLC). The results of the HER2-mutant cohort (cohort 2) have been reported elsewhere. Herein, we report the primary analysis of cohorts 1 and 1A, which aimed to evaluate the activity and safety of trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg in patients with HER2-overexpressing NSCLC. METHODS: Patients aged 18 years or older with unresectable or metastatic (or both unresectable and metastatic) non-squamous NSCLC who had relapsed following or were refractory to standard treatment or for whom no standard treatment was available, with an HER2 immunohistochemistry score of 3+ or 2+ (without known HER2 mutations) and an Eastern Cooperative Oncology Group performance status score of 0 or 1, were enrolled at 20 specialist hospitals in France, Japan, the Netherlands, Spain, and the USA. Patients were assigned to cohorts sequentially, first to cohort 1, to receive trastuzumab deruxtecan 6·4 mg/kg (cohort 1), then to cohort 1A, to receive trastuzumab deruxtecan 5·4 mg/kg, both administered intravenously once every 3 weeks. The primary endpoint was confirmed objective response rate by independent central review and was assessed in the full analysis set, which included all patients who signed an informed consent form and were enrolled in the study. Safety was assessed in all enrolled patients who received at least one dose of trastuzumab deruxtecan. This trial is registered with ClinicalTrials.gov, NCT03505710, and is ongoing (closed to recruitment). FINDINGS: Between Aug 27, 2018, and Jan 28, 2020, 49 patients were enrolled in cohort 1 (median age 63·0 years [IQR 58·0-68·0], 30 [61%] male, 19 [39%] female, and 31 [63%] White), and from June 16 to Dec 9, 2020, 41 patients were enrolled in cohort 1A (median age 62·0 years [IQR 56·0-66·0], 22 [54%] male, 19 [46%] female, and 31 [76%] White). As of data cutoff (Dec 3, 2021), the median treatment duration was 4·1 months (IQR 1·4-7·1) in cohort 1 and 5·5 months (1·4-8·7) in cohort 1A, and median follow-up was 12·0 months (5·4-22·4) in cohort 1 and 10·6 months (4·5-13·5) in cohort 1A. Confirmed objective response rate by independent central review was 26·5% (95% CI 15·0-41·1; 13 of 49, all partial responses) in cohort 1 and 34·1% (20·1-50·6; 14 of 41; two complete responses and 12 partial responses) in cohort 1A. The most common treatment-emergent adverse events of grade 3 or worse were neutropenia (12 [24%] of 49 in cohort 1, none in cohort 1A), pneumonia (six [12%] and two [5%], respectively), fatigue (six [12%] and three [7%], respectively), and disease progression (six [12%] and four [10%], respectively). Drug-related treatment-emergent adverse events of grade 3 or worse occurred in 26 (53%) of 41 patients in cohort 1 and nine (22%) of 49 patients in cohort 1A. Drug-related serious adverse events were reported in ten (20%) patients and three (7%) patients, respectively. Deaths due to treatment-emergent adverse events occurred in ten (20%) patients in cohort 1 (disease progression in six (12%) patients and bronchospasm, hydrocephalus, respiratory failure, and pneumonitis in one [2%] patient each), and in seven (17%) patients in cohort 1A (due to disease progression in four (10%) patients and dyspnoea, malignant neoplasm, and sepsis in one (2%) patient each). One death due to a treatment-emergent adverse event was determined to be due to study treatment by the investigator, which was in cohort 1 (pneumonitis). Independent adjudication of interstitial lung disease or pneumonitis found that drug-related interstitial lung disease or pneumonitis occurred in ten (20%) patients in cohort 1 (two [4%] grade 1, five [10%] grade 2, and three [6%] grade 5) and two (5%) patients in cohort 1A (one [2%] grade 2 and one [2%] grade 5). An additional patient in cohort 1A had grade 4 pneumonitis after the data cutoff, which was subsequently adjudicated as drug-related grade 5 interstitial lung disease or pneumonitis. INTERPRETATION: Given the low antitumour activity of existing treatment options in this patient population, trastuzumab deruxtecan might have the potential to fill a large unmet need in HER2-overexpressing NSCLC. Our findings support further investigation of trastuzumab deruxtecan in patients with HER2-overexpressing NSCLC. FUNDING: Daiichi Sankyo and AstraZeneca.
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Camptotecina , Carcinoma Pulmonar de Células não Pequenas , Imunoconjugados , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Pneumonia , Trastuzumab , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Progressão da Doença , Imunoconjugados/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pneumonia/induzido quimicamente , Receptor ErbB-2/genética , Receptor ErbB-2/análise , Trastuzumab/efeitos adversos , Trastuzumab/uso terapêuticoRESUMO
BACKGROUND: Which patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)-SCLC, to assess whether conventional NE markers are predictive of ICIs. METHODS: Patients with untreated ED-SCLC who received first-line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first-line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI-chemo group) and with chemotherapy alone (chemo group). RESULTS: A total of 227 patients were included in the ICI-chemo and chemo groups, respectively. The progression-free survival (PFS) tended to be better in patients in the ICI-chemo group than those treated with chemotherapy alone in patients with NE marker-positive SCLC. In particular, it was statistically significant in patients with chromogranin A-positive SCLC (p = 0.036). In patients with NE marker-negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker. CONCLUSION: Our study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker-negative SCLC.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Cromogranina A , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Inibidores de Checkpoint ImunológicoRESUMO
BACKGROUND: Although various companion diagnostic tests of ALK fusion gene-rearrangement are approved, few reports have assessed the concordance of ALK fusion gene-rearrangement in two companion diagnostic tests: next-generation sequencing (NGS) testing and immunohistochemistry (IHC). METHODS: The samples evaluated for gene alterations using NGS testing between May 2019 and November 2021 were included in this study. The inclusion criteria were as follows: samples were diagnosed with non-small cell lung cancer; the results of the NGS analysis were informative; and samples had residual specimens for IHC. We performed IHC on the residual specimens and retrospectively collected sample characteristics from medical records. RESULTS: A total of 185 samples were analyzed using NGS. Twenty-six samples were excluded because of failure to analyze gene alterations using NGS, no residual samples, and inadequate IHC. We analyzed 159 samples. The major histological type was adenocarcinoma (115 samples). The number of surgical and transbronchial lung biopsy specimens was 59 and 56, respectively. ALK fusion gene-rearrangement was detected in four samples using NGS, and five were detected using IHC. The sensitivity and specificity of IHC referred to by NGS were 75.0% and 98.7%, respectively. The concordance rate between IHC and NGS was 98.1%. ALK rearrangement was detected in two patients using IHC but not using NGS. In addition, ALK rearrangement was detected in one patient using NGS but not using IHC. CONCLUSION: Our results suggest that IHC and NGS might be complementary tests. In patients suspected of harboring ALK fusion gene-rearrangement, it should be analyzed using another diagnostic method.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Imuno-Histoquímica , Estudos Retrospectivos , Quinase do Linfoma Anaplásico/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
BACKGROUND: Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P-PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P-PEG as second-line chemotherapy for SCLC. METHODS: We retrospectively reviewed patients with SCLC who received AMR as second-line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P-PEG in their regimen, patients (n = 60) were divided into P-PEG (n = 21) and non-P-PEG groups, and their clinical outcomes were evaluated. RESULTS: Median of AMR treatment cycles was five (range: 1-39 cycles) in P-PEG group and four (range: 1-15 cycles) in non-P-PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P-PEG group than in the non-P-PEG group. The objective response rates were 52.4% and 30.8%, and median progression-free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P-PEG and non-P-PEG groups, respectively. CONCLUSIONS: AMR with P-PEG as second-line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P-PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
INTRODUCTION/BACKGROUND: The proper duration of immune checkpoint inhibitor (ICI) treatment for patients with advanced non-small cell lung cancer (NSCLC) remains unclear. Previously, sponsor-initiated clinical trials have more often used either a maximum 2-year fixed duration of ICI treatment or continuous treatment until documented disease progression. The study aimed to evaluate the association between ICI treatment duration (2-year fixed or continuous) and prognosis in patients with advanced NSCLC. PATIENTS AND METHODS: The medical records of 425 patients with NSCLC who received ICI before August 31, 2019 were retrospectively reviewed. RESULTS: No differences in time to treatment failure > 24 months (TTF-24) were detected between patients who underwent ICI treatment for > 2 years and patients who stopped ICI treatment at 2 years. Treatment-related adverse events tended to be higher in the patients with ICI treatment > 2 years. CONCLUSION: ICI treatment > 2 years did not significantly prolong the TTF compared with ICI treatment = 2 years, but it did increase the incidence of treatment-related adverse events.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Duração da Terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
B7 homolog 3 protein (B7-H3), an immune checkpoint molecule belonging to the B7 family, has been studied as a target for the development of anti-cancer treatment; however, changes in B7-H3 expression during the clinical course remain unknown. This retrospective study aimed to investigate changes in B7-H3 expression of lung cancer specimens in patients with advanced lung cancer following various anti-cancer treatments. The immunohistochemistry (IHC) score was evaluated on a 0-3 scale, and B7-H3 expression was considered positive for grade ≥ 2. The difference in IHC scores before and after anti-cancer treatment was defined as the change in B7-H3 expression. Among 160 patients with lung cancer who received anti-cancer treatment, 88 (55%) and 101 (63%) had B7-H3 expression before and after anti-cancer treatment, respectively. Before treatment, B7-H3 expression was significantly more common in squamous cell carcinoma specimens than in adenocarcinoma specimens (95% vs. 49%, P < 0.001). Of the 19 patients with squamous cell carcinoma, 18 (95%) continued to have high (IHC score: 3) B7-H3 expression following treatment. In contrast, of the 130 patients with adenocarcinoma, 46 (35%) and 17 (13%) showed an increased and a decreased expression, respectively. Patients who received targeted therapy had a significant increase in B7-H3 expression compared with those who received chemotherapy alone (P = 0.015). Overall, squamous cell carcinoma specimens maintained high B7-H3 expression during the clinical course, whereas adenocarcinoma specimens showed changes in expression following anti-cancer treatments. Our results provide the basis for further studies on the development of anti-cancer treatments targeting B7-H3.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Antígenos B7 , Neoplasias Pulmonares/patologia , Carcinoma de Células Escamosas/patologia , Adenocarcinoma/patologia , Progressão da DoençaRESUMO
PURPOSE: The initial brain metastasis velocity (iBMV) was recently reported as a survival predictor after brain metastases (BM) in patients treated by stereotactic radiosurgery. In this study, we validated whether iBMV is a prognostic tool, regardless of treatment modality, in patients with non-small cell lung cancer (NSCLC) with metachronous BM. METHODS: We retrospectively reviewed consecutive 3,792 new lung cancer cases in which no BM was found on magnetic resonance (MR) screening between February 2014 and December 2019, and enrolled 176 NSCLC patients with subsequent BM. Overall survival (OS) was calculated from the date of MR to identify the time from BM to death. RESULTS: The median iBMV score was 1.9. We used an iBMV score of 2.0 as the cutoff level, as previously reported. An iBMV score ≥ 2.0 was significantly associated with older age, high neutrophil-to-lymphocyte ratio, and Stage IV (P = 0.04, 0.02, and 0.02, respectively). The median OS was 0.92 years. The median OS for patients with iBMV score ≥ 2.0 and < 2.0 were 0.59 years and 1.33 years, respectively (P < 0.001). Multivariate analysis showed that an iBMV score ≥ 2.0, ECOG performance status score of 1-3, Stage IV, and non-adenocarcinoma histology were independent poor prognostic factors (hazard ratio (HR), 1.94; P = 0.0001; HR, 1.53; P = 0.04; HR, 1.45; P = 0.04; and HR, 1.14; P = 0.03, respectively). Patients with iBMV scores of < 2.0 were more likely to undergo craniotomy or stereotactic irradiation. CONCLUSIONS: An iBMV score ≥ 2.0 is an independent predictor of survival in NSCLC patients with metachronous BM, regardless of the treatment modality.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , PrognósticoRESUMO
Purpose: This study aimed to clarify the characteristics of and evaluate the risk factors for radiation pneumonitis (RP) induced by chemoradiation therapy (CRT) using accelerated hyperfractionated (AHF) radiation therapy (RT) in patients with limited-stage small cell lung cancer (LS-SCLC). Methods and Materials: Between September 2002 and February 2018, 125 patients with LS-SCLC were treated with early concurrent CRT using AHF-RT. Chemotherapy was comprised of carboplatin/cisplatin with etoposide. RT was administered twice daily (45 Gy/30 fractions). We collected data regarding onset and treatment outcomes for RP, and analyzed the relationship between RP and total lung dose-volume histogram findings. Uni- and multivariate analyses were performed to assess patient- and treatment-related factors for grade ≥2 RP. Results: The median age of patients was 65 years, and 73.6% of participants were men. In addition, 20% and 80.0% of participants presented with disease stage II and III, respectively. The median follow-up time was 73.1 months. Grades 1, 2, and 3 RP were observed in 69, 17, and 12 patients, respectively. Grades 4 to 5 RP were not observed. RP was treated with corticosteroids in patients with grade ≥2 RP, without recurrence. The median time from initiation of RT to onset of RP was 147 days. Three patients developed RP within 59 days, 6 within 60 to 89 days, 16 within 90 to 119 days, 29 within 120 to 149 days, 24 within 150 to 179 days, and 20 within ≥180 days. Among the dose-volume histogram parameters, the percentage of lung volume receiving >30 Gy (V30) was most strongly related to the incidence of grade ≥2 RP, and the optimal threshold to predict RP incidence was V30 ≥20%. On multivariate analysis, V30 ≥20% was an independent risk factor for grade ≥2 RP. Conclusions: The incidence of grade ≥2 RP correlated strongly with a V30 of ≥20%. Contrarily, the onset of RP induced by concurrent CRT using AHF-RT may occur later. RP is manageable in patients with LS-SCLC.
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Carboplatin plus etoposide is a standard treatment for older extensive-stage small-cell lung cancer (ES-SCLC) patients with performance status (PS) 2. However, older patients often exhibit poor PS (3, 4), and the treatment effect in them is poorly understood. To determine the therapeutic efficacy and safety of carboplatin plus etoposide therapy for this population, we retrospectively analyzed 63 patients with ES-SCLC with PS ≥2, aged ≥71 years, who had received first-line carboplatin plus etoposide therapy. We compared the treatment efficacy and safety in patients with baseline PS 2 versus those with PS 3-4. In the PS 2 (38 patients) and PS ≥3 (25 patients) groups, the overall response rate was 71.1% and 72.0%, median progression-free survival was 4.6 and 3.1 months, and overall survival was 7.7 and 5.1 months, respectively. PS improved to 0-1 post-treatment in 65.8% and 48.0% of the patients in the PS 2 and PS ≥3 groups, respectively. Patients with PS ≥3 showing improved PS had a progression-free survival of 6.1 months. A higher incidence of grade ≥3 decreased neutrophil counts, febrile neutropenia, and treatment-related death was observed in the PS ≥3 group. The progression-free survival of patients administered prophylactic granulocyte colony-stimulating factor (G-CSF) was 5.2 and 6.1 months in the PS2 and PS ≥3 groups. Overall, carboplatin plus etoposide therapy provided comparable tumor shrinkage, but shorter progression-free and overall survival in older ES-SCLC patients with PS ≥3 than in those with PS 2. Thus, supportive care, such as prophylactic G-CSF administration, may be necessary to ensure safety and survival.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Idoso , Carboplatina , Etoposídeo , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/patologia , Fator Estimulador de Colônias de GranulócitosRESUMO
BACKGROUND: Tyrosine kinase inhibitors (TKIs) are effective for the treatment of non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR), but responses are not durable as tumors develop resistance. DS-1205c is a novel, specific, orally bioavailable, small-molecule AXL receptor TKI. In preclinical studies, DS-1205c restored TKI antitumor activity in a TKI acquired-resistance EGFR-mutant NSCLC tumor xenograft model. METHODS: This first-in-human, multicenter, open-label Phase 1 study (registered at ClinicalTrials.gov: NCT03599518) primarily evaluated the safety and tolerability of combination therapy with DS-1205c and gefitinib in Japanese patients with metastatic or unresectable EGFR-mutant NSCLC and tumor progression during treatment with EGFR-TKIs. Patients (n = 20) received DS-1205c monotherapy (200-1200 mg twice daily [BID]) in a 7-day safety monitoring period before combination DS-1205c/gefitinib (250 mg once daily) in 21-day cycles. RESULTS: The observed common treatment-emergent adverse events (TEAEs) were increased aspartate aminotransferase (35%), increased alanine aminotransferase (30%), rash maculo-papular (30%), and diarrhea (25%). No serious TEAEs were reported. Plasma concentrations and pharmacokinetic parameters of DS-1205a (free form of DS-1205c) were unaffected by concomitant administration of gefitinib. No patient achieved a complete or partial response and 5 patients (25%) had stable disease. CONCLUSION: DS-1205c was generally safe and well tolerated at all dose levels, but the safety profile of ≤800 mg BID was more favorable than 1200 mg BID. The recommended dose for dose-expansion cohorts of DS-1205c in combination therapy with gefitinib was 800 mg BID.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Mutação , Receptores ErbB/genéticaRESUMO
BACKGROUND: Programmed cell death 1 (PD-1)/programmed cell death ligand (PD-L1) inhibitors plus chemotherapy (ICI + Chemo) is the standard treatment for advanced non-small-cell lung cancer (NSCLC). However, the impact of tumour burden on the efficacy of ICI + Chemo remains unknown. METHODS: We retrospectively evaluated 92 patients with advanced NSCLC treated with ICI + Chemo. Tumour burden was assessed as the sum of the longest diameter of the target lesion (BSLD) and number of metastatic lesions (BNMLs). We categorised the patients into three groups based on the combined BSLD and BNML values. RESULTS: Sixty-eight patients (74%) had progressive disease or died. Forty-four patients (48%) in the low-BSLD group had a median progression-free survival (PFS) of 9.5 months, whereas patients in the high-BSLD group had a median PFS of 4.6 months (hazard ratio [HR] = 0.54, p = 0012). Twenty-five patients (27%) in the low-BNML group had a median PFS of 9.6 months, whereas patients in the high-BNML group had a median PFS of 6.5 months (HR = 0.51, p = 0.029). Low-BSLD and low-BNML were associated independently with improved PFS in multivariate analysis. Analysis of the tumour burden combined with BSLD and BNML revealed a trend towards improved PFS as the tumour burden decreased, with median PFS of 22.3, 8.7, and 3.9 months in the low- (N = 13), medium- (N = 42) and high-burden (N = 37) groups respectively. CONCLUSIONS: Our findings demonstrated that a high tumour burden negatively impacts the efficacy of ICI + Chemo in patients with advanced NSCLC.