Publications by authors named "Hiroaki Akamatsu"

Background: Chemoimmunotherapy is the standard first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC); however, its real-world long-term outcomes associated with patient backgrounds are still unclear. We explored this association using an updated large real-world prospective cohort with a minimum follow-up of 3 years.

Methods: This prospective cohort study, conducted across 32 hospitals, enrolled patients with ES-SCLC receiving carboplatin, etoposide, and atezolizumab between September 1, 2019 and September 30, 2020.

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Background: Lung mucinous adenocarcinoma has various genetic alterations, but there are no reported cases with exon 14 skipping mutations. Multiplex genetic testing is commonly assessed in non-small cell lung cancer (NSCLC) and treatment usually comprises molecular targeted drugs. However, the efficacy of molecular targeted drugs in lung mucinous adenocarcinoma is not reported.

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Objectives: Programmed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting.

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What Is This Summary About?: This is a summary of a phase 2 clinical study called DeLLphi-301. The study looked at how effective and safe a medicine called tarlatamab was in participants with small cell lung cancer (SCLC). Participants previously received at least two other treatments for their SCLC.

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Objectives: The impact of cGAS/STING tumor expression on PD-1/L1 inhibitor efficacy and the tumor microenvironment remain to be elucidated.

Methods: In a post-hoc analysis of a prospective biomarker study with 106 advanced NSCLC patients treated with PD-1/L1 inhibitors from December 2015 to September 2018, tumor tissue before treatment from 68 patients was analyzed. cGAS and STING expression were measured using immunohistochemical staining and H-scores.

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Article Synopsis
  • The study aimed to investigate the relationship between immune-related adverse events (irAEs) and the effectiveness of immune checkpoint inhibitor therapy in cancer patients, particularly focusing on overall and progression-free survival.
  • In a cohort of 1,002 Japanese patients with advanced non-small cell lung cancer treated with atezolizumab, 19% experienced irAEs, predominantly skin disorders and interstitial lung disease.
  • Results showed that patients with irAEs had better overall survival compared to those without, especially those with low-grade irAEs, indicating potential clinical benefits from irAEs in real-world settings, except for high-grade events unrelated to skin or endocrine disorders.
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Several predictive factors of immune checkpoint inhibitor response have been reported, but there has not been sufficient exploration of which patients benefit from immune checkpoint inhibitor rechallenge. We report the case of a patient with non-small cell lung cancer who had 6 years of complete response with initial nivolumab treatment. After relapse, however, rechallenge with nivolumab did not result in tumour shrinkage or long-term response.

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Neoadjuvant therapy with nivolumab improves event-free survival (EFS) in patients with resectable non-small cell lung cancer, and a pathological complete response is a predictor of longer EFS. We assessed metabolic responses using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) before and after neoadjuvant treatment to explore its surrogacy for pathological complete response (pCR). We describe three patients with squamous cell lung carcinoma who underwent neoadjuvant therapy with nivolumab plus chemotherapy, followed by surgery.

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  • A phase 3 trial evaluated the effectiveness of adding a CTLA-4 inhibitor to standard platinum-based chemotherapy and PD-1/PD-L1 inhibitors for patients with advanced non-small-cell lung cancer, as no prior studies had focused on this combination's survival benefits.
  • Conducted across 48 hospitals in Japan, the trial involved patients aged 20+ with untreated NSCLC, but had to stop recruitment early due to a concerning number of treatment-related deaths in the nivolumab-ipilimumab group.
  • The final results indicated no significant difference in overall survival between those receiving pembrolizumab and those receiving nivolumab-ipilimumab, with median survival rates of 23.7 months and 20.5
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  • This study analyzed pharmacokinetic (PK) data for atezolizumab, an immunotherapy drug, in Japanese patients with non-small cell lung cancer (NSCLC), focusing on a dosing regimen of 1200 mg every three weeks.
  • Researchers evaluated data from 262 patients, measuring plasma drug levels before the third treatment cycle and examining how these levels correlated with treatment effectiveness and the occurrence of adverse events (AEs).
  • Findings indicated that lower plasma levels of atezolizumab were linked to shorter overall survival, while higher drug concentrations were associated with increased AEs, suggesting the importance of monitoring PK levels for better treatment outcomes.
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  • A Phase III study tested the efficacy of subcutaneous versus intravenous amivantamab for patients with advanced non-small cell lung cancer (NSCLC) who had progression after prior treatments.
  • Results showed that the subcutaneous form maintained efficacy, with fewer side effects and a significantly longer overall survival, while also being more convenient to administer.
  • Patients receiving subcutaneous amivantamab had less infusion-related reactions and faster administration times, with 85% finding the treatment convenient compared to only 35% in the intravenous group.
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The standard treatment for resectable non-small cell lung cancer (NSCLC) located in the superior sulcus is neoadjuvant chemoradiotherapy followed by highly invasive resection. Based on the results of the CheckMate 816 trial, which showed a marked improvement in the efficacy of neoadjuvant chemo-immunotherapy, we report a case of minimally invasive resection after neoadjuvant nivolumab plus chemotherapy for superior sulcus NSCLC, resulting in a pathologic complete response. The patient was a 76-year-old man with a 65-mm right superior sulcus tumour diagnosed as squamous cell carcinoma with 95% PD-L1.

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CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear.

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Background: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification.

Methods: This is a prospective, single-centered, open-label, noninferiority phase II study.

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Background: In small-cell lung cancer (SCLC), the tumor immune microenvironment (TIME) could be a promising biomarker for immunotherapy, but objectively evaluating TIME remains challenging. Hence, we aimed to develop a predictive biomarker of immunotherapy efficacy through a machine learning analysis of the TIME.

Methods: We conducted a biomarker analysis in a prospective study of patients with extensive-stage SCLC who received chemoimmunotherapy as the first-line treatment.

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Article Synopsis
  • Biomarker testing for driver mutations in non-small cell lung cancer (NSCLC) is crucial for treatment selection, yet current practices in Japan reveal limitations.
  • The REVEAL cohort study involved data collection from 29 institutions, examining 1479 patients diagnosed with advanced or recurrent NSCLC to assess biomarker testing and treatment issues.
  • The study found that while 86.1% of patients had confirmed biomarker status, there were varying positivity rates among different gene tests, indicating challenges in effective treatment decisions based on biomarker testing.
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Background: An association exists among the diagnostic yield of transbronchial biopsy using endobronchial ultrasonography with a guide sheath (EBUS-GS-TBB) and several factors, such as simple within or adjacent endobronchial ultrasonography (EBUS) findings. Here, we aimed to investigate whether more detailed EBUS findings affect the diagnostic yield of lung cancer in EBUS-GS-TBB.

Methods: We conducted this retrospective single-center cohort study, enrolling consecutive patients with lung cancer who underwent EBUS-GS-TBB.

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Context: The efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation.

Objectives: The primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care.

Methods: In this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled.

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Background: Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes.

Methods: We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the ) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles.

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  • The phase III IMPACT study evaluated the effectiveness of adjuvant gefitinib compared to cisplatin plus vinorelbine (cis/vin) for patients with completely resected EGFR-mutated non-small cell lung cancer (NSCLC).
  • Although the study didn't meet its main goal of improving disease-free survival (DFS), researchers focused on identifying molecular predictors of gefitinib's effectiveness among 202 patients analyzed for cancer-related gene mutations.
  • Key findings revealed that NOTCH1 co-mutations indicated a poorer overall survival in the gefitinib group, while CREBBP co-mutations suggested better outcomes in terms of DFS and overall survival for the cis/vin group.
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  • Tarlatamab is a bispecific T-cell engager immunotherapy that showed promising results in a phase 1 trial for patients with previously treated small-cell lung cancer.
  • In a phase 2 trial involving 220 patients, tarlatamab was administered intravenously every 2 weeks at doses of 10 mg or 100 mg, with an objective response rate of 40% and 32% respectively.
  • The study found that common side effects included cytokine-release syndrome, decreased appetite, and fever, with overall survival rates at 9 months being 68% for the 10-mg group and 66% for the 100-mg group.
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Background: The ALTA-1L study compared brigatinib with crizotinib in untreated ALK-rearranged non-small cell lung cancer (NSCLC) patients, demonstrating the efficacy of brigatinib. Although the median progression-free survival (PFS) of brigatinib group was 24.0 months, the one-year PFS rate was 70%.

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  • The ONO-4538-52/TASUKI-52 study evaluated the effectiveness and safety of nivolumab combined with chemotherapy and bevacizumab for treating advanced non-squamous non-small cell lung cancer (nsNSCLC) in Japan, Korea, and Taiwan.
  • At the interim analysis, patients receiving nivolumab showed significantly longer progression-free survival compared to those who received a placebo, although overall survival data was still early.
  • An updated analysis revealed that patients in the nivolumab group had a median overall survival of 30.8 months versus 24.7 months for the placebo group, suggesting that the nivolumab regimen could be a standard first-line treatment for this type of lung cancer.
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