092-642-3578

092-642-5390

Bachelor of Medicine

Respiratory medicine

00years00months

I practice at the Cancer Center and the Department of Respiratory Medicine of Kyushu University Hospital. I am involved in the operation and management of outpatient chemotherapy rooms and the reiview of chemotherapy regimens at Kyushu University Hospital. I also give lectures for 3rd year undergraduates, lectures for 5th year undergraduate ward practice, lectures for cancer professional graduate students, and guidance for interns. As clinical researches, I serve as the research office for five investigator initiated clinical trials.

Research Interests

• To develop new treatments for lung cancer and establish standard treatments through various clinical trials.
  keyword : lung cancer, clinical trial, immune checkpoint inhibitor, chemotherapy
  2022.03～2027.03.

Current and Past Project

• The standard of care for advanced non-small cell lung cancer (NSCLC) is platinum combination chemotherapy plus immune checkpoint inhibitors. Inhibition of vascular endothelial growth factor (VEGF) by bevacizumab enhances the efficacy of cytotoxic anticancer agents, but it is also expected to enhance the efficacy of immune checkpoint inhibitors via normalization of tumor vasculature, increasing T-cell infiltration, and promoting dendritic cell maturation. Therefore, we planned and performed the primary analysis of a multicenter, randomized, phase III trial to evaluate the effect of adding bevacizumab to PD-1/PD-L1 antibody and platinum-based combination chemotherapy in the treatment of advanced non-squamous NSCLC.
• It has been reported that TTF-1-negative nonsquamous non-small cell lung cancer has a poorer prognosis than TTF-1-positive nonsquamous non-small cell lung cancer and tends to respond poorly to pemetrexed-based drug therapy, which is highly effective in nonsquamous cancer. In our retrospective study, pemetrexed-based chemotherapy plus immune checkpoint inhibitors were also less effective in TTF-1-negative nonsquamous non-small cell lung cancer. Therefore, we designed and initiated a phase II study to evaluate the efficacy of carboplatin plus nab-paclitaxel plus atezolizumab as a potential alternative to pemetrexed-based regimens for TTF-1-negative nonsquamous non-small cell lung cancer.
• In advanced non-small cell lung cancer, brain metastases account for approximately 20% of patients at the time of initial diagnosis. Platinum-based chemotherapy has so far been ineffective in treating brain metastases, and radiotherapy and surgery have often been chosen as local therapies. However, radiotherapy is known to cause long-term adverse events such as cognitive decline, and surgery has the disadvantage of being invasive, which delays the introduction of systemic therapy. Therefore, it is an important clinical issue how to control brain metastases by systemic therapy. The introduction of immune checkpoint inhibitors has improved the efficacy of systemic therapy for brain metastases, and in particular, the combination of chemotherapy plus nivolumab and ipilimumab has been reported to be promising for brain metastases. Therefore, we designed and conducted a phase II study to evaluate the efficacy and safety of platinum-based chemotherapy plus nivolumab plus ipilimumab in advanced non-small cell lung cancer with untreated brain metastases.
• With the recent introduction of immune checkpoint inhibitors, combination therapy with platinum-based chemotherapy and immune checkpoint inhibitors (PD-L1 inhibitors) has been established as the standard treatment for advanced small cell lung cancer. About 25% of patients with advanced small cell lung cancer have brain metastases at the time of initial diagnosis. Brain metastases directly affect the quality of life of patients, and controlling brain metastases has been a clinically important issue for many years. However, the effects of platinumm-based chemotherapy and a PD-L1 inhibitor on brain metastasis (e.g., intracranial tumor response and duration of brain metastasis control) have not been clarified. Therefore, we designed and initiated a single-arm phase II study to evaluate the efficacy of platinum plus etoposide with durvalumab to brain metastases of small cell lung cancer.
• The first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) is combination therapy with an immune checkpoint inhibitor (ICI) and platinum-based chemotherapy. However, phase III trials of combination therapy with platinum-based chemotherapy and ICI have only included patients with preserved organs function, and there is no information on efficacy and safety in patients with impaired renal function. Therefore, we designed and initiated a phase II study to evaluate the efficacy and safety of carboplatin plus nab-paclitaxel with atezolizumab, a combination of platinum and ICI that may be feasible to administer in patients with impaired renal function.
• 　Non-small cell lung cancer is the leading cause of cancer death, accounting for 85% of all lung cancer cases, and more than half of these cases have advanced disease with distant metastasis at diagnosis. The introduction of molecular-targeted therapies has led to a dramatic improvement in treatment outcomes. On the other hand, for untreated advanced non-small cell lung cancer patients with negative driver gene mutations, platinum-based chemotherapy plus pembrolizumab (anti-PD-1 antibody) was shown to significantly improve survival compared to platinum-based chemotherapy, which has been the standard of care. At the American Society of Clinical Oncology meeting in 2020, a four-drug combination immunotherapy consisting of platinum-based chemotherapy (two cycles) plus nivolumab (anti-PD-1 antibody) plus ipilimumab (anti-CTLA-4 antibody) significantly extended survival compared to platinum-based combination therapy. The results of this study have attracted much attention, as they show that combined immunotherapy using four drugs (anti-PD-1 antibody + ipilimumab (anti-CTLA-4 antibody)) significantly prolongs survival compared to platinum combination therapy, and also shows promise in providing the long-term survival expected of immunotherapy.
  　In this randomized, controlled phase III trial, we tested the superiority of the investigational combination platinum therapy (2 cycles) plus nivolumab plus ipilimumab over standard therapy (platinum combination therapy plus pembrolizumab) in overall survival in patients with untreated advanced non-small cell lung cancer with negative or unknown driver genes. The study (JCOG 2007) was conducted in Japan. The study (JCOG 2007) was conducted by the Japan Clinical Oncology Group (JCOG) as a multicenter study at 55 centers nationwide, with a planned enrollment of 422 patients and a planned enrollment period of 3 years.
  　Although enrollment exceeded the planned pace, more treatment-related deaths (TRD) occurred in the nivolumab plus ipilimumab arm than expected. To ensure the safety of enrolled patients, we revised eligibility criteria (e.g., excluding patients with white blood cell counts > 8,600/mm3 and NLR (neutrophil to lymphocyte ratio) > 5). However, TRD continued to occur in the nivolumab plus ipilimumab group, ultimately resulting in a TRD rate of 11/148 patients (7.5%), with the main causes of TRD being cytokine release syndrome, myocarditis and pneumonia. Since no reliable strategy to predict and prevent TRD in the nivolumab plus ipilimumab arm was found, we prematurely terminated this study on March 30, 2023, when 295 patients had been enrolled.
  　The National Cancer Center announced a press release on April 28, 2023 regarding the TRD that occurred in the nivolumab + ipilimumab arm.
  In addition, the TRD and cytokine release syndrome, a characteristic adverse event in this study, were reported in international journals as a letter and a case report, respectively. We prioritized the immediate publication of the efficacy as well as the safety of this study and conducted the primary analysis. The median overall survival for chemotherapy plus nivolumab plus ipilimumab was 23.7 months (95% CI 17.6 months to not reached), and for chemotherapy plus pembrolizumab was 20.5 months (95% CI 17.6 months to not reached), with a hazard ratio of 0.98 (90% CI 0.72-1.34). 72 to 1.34), one-sided P value 0.46 (>0.05), and there was no difference in overall survival between the two groups. With regard to toxicity, not only TRD but also Grade 3 or higher non-hematologic toxicity occurred more frequently in the nivolumab + ipilimumab group. Considering the risk-benefit profile, we concluded that platinum plus pembrolizumab remains the standard of care in untreated advanced non-small cell lung cancer with negative or unknown driver genes. The results of the main analysis are being submitted for publication. An updated analysis will be performed in April 2026.

Academic Activities

Educational Activities