Japanese journal of clinical oncology最新文献

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).

Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off). Dual primary endpoints were OS and PFS, assessed by blinded independent central review. Secondary endpoints were objective response rate (ORR) and safety.

Results: The East Asian subgroup comprised 130 patients (pembrolizumab-axitinib, n = 62; sunitinib, n = 68; 15.1% of the global intention-to-treat population). Compared with sunitinib, pembrolizumab-axitinib OS hazard ratio (HR) was 0.85 [95% confidence interval (CI) 0.50-1.44; 36-month rates, 62.9% and 58.8%, respectively] and PFS HR was 0.59 (95% CI 0.38-0.92) in favor of pembrolizumab-axitinib. ORR favored pembrolizumab-axitinib (64.5% vs 44.1% for sunitinib). The results were generally consistent with the intention-to-treat population. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 69.4% of patients on pembrolizumab-axitinib and 74.6% on sunitinib; 16 (25.8%) patients on pembrolizumab-axitinib and 17 (25.4%) patients on sunitinib discontinued due to adverse events. No deaths from TRAEs occurred.

Conclusion: Pembrolizumab-axitinib improved efficacy for East Asian patients with untreated clear cell mRCC, consistent with results from the global population. Safety was manageable. ClinicalTrials.gov identifier: NCT02853331.

Background: Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) regimen has been established as a systemic chemotherapy for patients with urothelial carcinoma. However, it is rarely used in Japan owing to the challenges associated with managing the related adverse events. This study aimed to optimize the dd-MVAC protocol for Japanese patients.

Methods: Criteria were developed to adjust the doses of anticancer drugs used in dd-MVAC. In this regimen, the initial cycle of methotrexate and cisplatin was administered at 75% of the full dose. Patients who did not experience significant toxicities during the first cycle subsequently received the full dose starting from the second cycle. Additionally, the doses of methotrexate and cisplatin were adjusted according to the Cockcroft-Gault creatinine clearance. Based on these criteria, patients with urothelial carcinoma underwent dd-MVAC between August 2018 and May 2023, and all patients were scheduled to undergo six cycles.

Results: A total of 86 patients received dd-MVAC, with 36, 15, and 35 patients receiving it as neoadjuvant, adjuvant, and salvage chemotherapy, respectively. Fifty-nine patients (68.6%) completed the six scheduled cycles. Grade ≥ 3 toxicities of Common Terminology Criteria for Adverse Events were observed in 76 (88.4%) patients; however, most were manageable. In the neoadjuvant cohort, the pathological complete response rate was 52.2% among patients with clinical N0 lower tract urothelial carcinoma. High levels of alkaline phosphatase at the initiation of treatment were correlated with failure to complete six cycles of dd-MVAC.

Conclusion: Adjusting the dd-MVAC regimen based on renal function and significant adverse events may result in a high completion rate of scheduled treatments in Japanese patients with urothelial carcinoma.

Background: In Japan, about 70%-80% of cancer deaths occur in hospitals. The actual number of cancer patients who die in hospitals where palliative care is available is not clear. This study aimed to examine whether hospitals where cancer patients died offered palliative care.

Methods: Patients aged ≥20 who died of cancer in 2018 were included. We used the Japanese death records and publicly available data on hospital functions. Cancer death numbers and hospitals were summarized according to hospital function and age group. Logistic regression analysis was performed to examine the death influence in patients with cancer in designated cancer hospitals.

Results: The study included 302 511 patients, and 168 835 patients (55.8%) died in hospitals with palliative care. In hospitals without palliative care, those with 100-199 and 200-499 beds had more deaths than hospitals not in these ranges of beds. Their median number of deaths per year was 17 and 26, respectively. Categorized by the death numbers per hospital without palliative care, hospitals with 20-49 cancer deaths were common. In the designated cancer hospitals, younger patients aged 20-29 had a higher odds ratio (OR) for death (4.28) than those aged 70-79. Blood cancer had a higher OR (2.36) than colorectal and rectal cancer.

Conclusion: Our findings suggest that outreach of palliative care to hospitals with 100-199 or 200-499 beds and 20-49 deaths lacking palliative care could effectively improve end-of-life cancer care.

Background: JCOG1113 is a randomized phase III trial that showed non-inferiority of gemcitabine plus S-1 to gemcitabine plus cisplatin in patients with advanced biliary tract cancer. Assessment of inter-institutional heterogeneity in chemotherapy contributes to confirm generalizability and reliability of the study itself. However, there have been no studies conducted to assess the heterogeneity among participating centers in randomized phase III trials for biliary tract cancer.

Methods: The objective of this post-hoc analysis was to assess the inter-institutional heterogeneity in the overall survival and progression-free survival of patients with advanced biliary tract cancer treated with first-line chemotherapy in the JCOG1113 trial. The heterogeneity in the overall survival and progression-free survival was assessed according to three factors: hospital volume, experience in medical oncology and experience in biliary intervention. A total of 300 advanced biliary tract cancer patients were analyzed. There were no statistically significant trends observed between hospital volume, experience in medical oncology, or experience in biliary intervention and overall survival (hospital volume: adjusted trend P value = 0.6796; experience in medical oncology: adjusted trend P value = 0.4092; experience in biliary intervention: adjusted trend P value = 0.6112). Similarly, no statistically significant trends were observed between these factors and progression-free survival (hospital volume: adjusted trend P value = 0.3000; experience in medical oncology: adjusted trend P value = 0.1108; experience in biliary intervention: adjusted trend P value = 0.2898).

Conclusions: This study revealed no inter-institutional heterogeneity in the overall survival and progression-free survival in the JCOG1113 study population of advanced biliary tract cancer patients.

Objective: This research aimed to establish the inaugural evidence-based cancer survivorship guidelines for Japan, with a particular focus on exercise and physical activity, in order to enhance health outcomes for cancer survivors.

Methods: A panel of experts, including oncologists, physicians, exercise scientists, epidemiologists and patient advocates, utilized a modified Delphi process and systematic reviews to establish consensus on exercise recommendations for cancer survivors. The panel focused on setting the objectives of the Clinical Practice Guidelines and addressing crucial clinical issues in Japan. Recommendations were formulated based on the strength and certainty of evidence, the benefit-harm balance and patient values and preferences.

Results: The panel formulated exercise recommendations for cancer survivors of two age groups: 18-64 years and ≥65 years. The recommendations for both age groups are consistent, emphasizing the importance of regular exercise and physical activity tailored to individual capabilities and health conditions. The guidelines underline the benefits of exercise in improving the overall health and quality of life of cancer survivors. This consensus on exercise recommendations marks a significant step in the development of comprehensive cancer survivorship guidelines in Japan, with potential implications for improving clinical outcomes and advancing research in cancer survivorship.

Conclusions: These guidelines will serve as a critical resource for cancer survivors, highlighting exercise as a key component of survivorship care, and for clinicians, in recommending appropriate physical activities to improve survivor health and well-being.

Background: Prognostic predictors of immunotherapy in patients with advanced endometrial cancer remain unclear. The potential role of inflammatory predictors, including pretreatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet scores, was investigated.

Methods: Between August 2018 and December 2023, 35 patients were retrospectively analyzed. Prognostic predictors were compared, and optimal cut-off values that exhibited the greatest discrimination for overall response, disease control, progression-free survival and overall survival were determined. Multivariate analysis was used to assess the prognostic significance of the predictors.

Results: The greatest discrimination for overall response, progression-free survival and overall survival included platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet; the areas under the curve were 0.638, 0.649 and 0.641, respectively. The precise cut-off values of neutrophil-to-lymphocyte ratio for progression-free survival and overall survival were 4.92 and 5.40, respectively. The lower neutrophil-to-lymphocyte ratio group had a significantly longer progression-free survival (P = 0.001, median survival; 4.0 months vs. 19 months) and longer overall survival (P = 0.002, median survival; 5.0 months vs. 21 months). Of the risk factors assessed, neutrophil-to-lymphocyte ratio (hazard ratio = 4.409; 95% CI = 1.10-17.64; P = 0.036) and regimen (hazard ratio = 5.559; 95% CI = 1.26-24.49; P = 0.023) were independently correlated with overall survival.

Conclusion: In patients with advanced endometrial cancer, pretreatment neutrophil-to-lymphocyte ratio may be a prognostic predictor of those who would benefit from immunotherapy.