Japanese journal of clinical oncology最新文献

Objective: In Japan, selumetinib is used in pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibroma (PN). However, there have been no real-world reports on Japanese patients. In this study, we reported a single-center, short-term experience with selumetinib after its approval in Japan.

Methods: We prospectively collected data from 11 pediatric NF1 patients with symptomatic, inoperable PN who were initiated on selumetinib between November 2022 and May 2023; the selumetinib was administered by the same physician. Various patient factors, tumors, dose and efficacy of selumetinib, and adverse events (AE) were investigated.

Results: Of 11 patients included, 7 were male, with a mean age of 14 years. The sites of symptomatic main PN included the head and neck, pelvis to lower extremities, and paraspinal lesions in five, three, and three patients, respectively. The median maximum diameter of the main PN was 91 mm, and the median follow-up duration was 19 months. All patients with pain or motor dysfunction experienced symptom improvement after treatment, and the tumors tended to shrink in 7 of the 11 patients (64%). Among the six patients with disfigurements, only one experienced improvement. Of 59 AEs observed, 58 (98%) were grades 1 and 2, and 5 patients (46%) underwent temporary selumetinib withdrawal due to AEs. One patient discontinued the drug (9%) because of rash dermatitis.

Conclusions: Despite the relatively short-term results, no serious AEs were observed, and many patients benefited from selumetinib treatment. In some patients, administration was discontinued or interrupted because of the balance between benefits and AEs, and further data are needed to better understand the general safety and efficacy of selumetinib.

Objective: This study aimed to assess the oncological outcomes of the subtype of urothelial carcinoma (SUC), including divergent differentiation and histologic subtype, in comparison with those of pure urothelial carcinoma (PUC) in nonmuscle-invasive bladder cancer.

Methods: We retrospectively evaluated patients who were initially treated with transurethral resection of the bladder tumor (TURBT) between March 2005 and August 2020 at a single institution. Patients with PUC and SUC were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS).

Results: Out of 853 enrolled patients, 783 (91.8%) and 70 (8.2%) had PUC and SUC, respectively. SUC presence was significantly associated with old age, tumor size (≥3 cm), higher pT1 rate, high grade, concomitant carcinoma in situ, and lymphovascular invasion. RFS rates after TURBT did not significantly differ between the PUC and SUC groups. With a median follow-up period of 66 months (interquartile range, 38-103 months), the rates and median time of progression to muscle invasion were 6.9% and 22.5 months in the PUC group, and 22.9% and 10.0 months in the SUC group. Moreover, the incidence of progression to metastasis was 4.6% and 15.7% in the PUC and SUC groups, respectively. The 5-year PFS rates (64.5% and 81.9%, P < .001) and 5-year OS rates (71.7% and 86.2%, P = .009) were lower in the SUC group than in the PUC group. On multivariate analysis, SUC presence independently predicted progression to muscle invasion and metastasis.

Conclusion: At initial TURBT diagnosis, we must pay more attention to higher progression risk of SUC than that of PUC in nonmuscle-invasive bladder cancer.

Objective: To describe standard of care and inform the evolving unmet need among extensive stage small-cell lung cancer (ES-SCLC) patients in Japan since approval of first-line anti-PD-L1 therapies, we describe treatment patterns and overall survival by line of therapy.

Methods: We conducted a descriptive analysis of adult ES-SCLC patients in Japan using de-identified patient data within the MDV database (hospital-based claims) to describe treatment patterns and DeSC database (payer-based claims linked to mortality of municipality records) to describe both treatment patterns and real-world overall survival (rwOS).

Results: The study population of MDV and DeSC cohorts included 6302 and 903 patients, respectively. First-line anti-PD-L1 therapy-based regimens grew since their approval in 2019 and were used in ~35% and ~59% of patients in 2022, in the MDV and DeSC cohorts, respectively. Amrubicin monotherapy was the most common second-line (2 L) regimen before and after 1 L anti-PD-L1 approvals. No clear standard of care was identified in third-line (3 L) and fourth-line (4 L). Median rwOS following 1 L therapy was 10.6 months (95% CI: 9.0, 11.8) and 9.3 months (95% CI: 8.3, 10.3) in patients who did and did not receive anti-PD-L1 therapy, respectively. Following 2 L, 3 L, and 4 L therapy, median rwOS was 6.7 months (95% CI: 5.9, 7.4), 5.5 months (95% CI: 4.4, 6.4), and 4.7 months (95% CI: 3.4, 6.9), respectively.

Conclusions: Anti-PD-L1 therapies have become part of first-line standard of care but survival in treated Japanese ES-SCLC patients remains poor, highlighting the unmet medical need in the post anti-PD-L1 era.

Introduction: Osimertinib-induced interstitial lung disease in untreated EGFR-mutated, advanced non-small cell lung cancer is being reported at a higher rate in Japan than elsewhere. However, data on the interstitial lung disease incidence during first-line osimertinib therapy and the course of lung cancer treatments administered after interstitial lung disease onset in the real-world setting are scarce.

Materials and methods: The present study reviewed the data from the Reiwa study, a multicentric, observational study examining the efficacy and safety of first-line osimertinib therapy in the clinical setting. Patients with EGFR-mutated non-small cell lung cancer who began osimertinib therapy between September 2018 and August 2020 were enrolled and followed until August 2022.

Results: Among 583 patients receiving first-line osimertinib therapy, 75 (12.8%) had interstitial lung disease development, and 18 (3.0%) had at least grade 3 interstitial lung disease. Fifty-nine patients (78%) received some form of treatment following interstitial lung disease onset. An epidermal growth factor receptor-tyrosine kinase inhibitor rechallenge was performed in 31 patients (41%), with 18 (24%) receiving osimertinib again. Interstitial lung disease recurred in five (28%) of these 18 patients, none of 13 patients receiving another type of tyrosine kinase inhibitor, and seven (25%) of 28 patients receiving chemotherapy and/or immune checkpoint inhibitor therapy. The median overall survival after the initial osimertinib therapy was 38.4 months and 12.2 months for patients with interstitial lung disease grade 1-2 and grade 3-4, respectively (hazard ratio: 0.37; 95% confidence interval: 0.20-0.70; P = 0.002).

Conclusion: Patients with interstitial lung disease grade 3-4 had poorer survival during the first-line osimertinib therapy. A substantial risk of interstitial lung disease recurrence was associated with post-osimertinib therapy. Trial registration code: UMIN000038683.

Objectives: The introduction of novel drugs for metastatic castration-sensitive prostate cancer has expanded treatment options for patients. Associated changes in healthcare resource utilization may have occurred in tandem, but nationwide information is limited. This study aimed to describe initial treatment patterns and healthcare resource utilization (including costs) for patients with metastatic castration-sensitive prostate cancer in routine clinical practice in Japan.

Methods: This retrospective, longitudinal cohort study used a large-scale claims database covering acute care hospitals of various sizes. Included were men who received first medical treatment for metastatic castration-sensitive prostate cancer between January 2015 and July 2021 (identification period). The primary endpoint was the initial treatment pattern for metastatic castration-sensitive prostate cancer.

Results: Among 7665 men with metastatic castration-sensitive prostate cancer, the median (Q1, Q3) duration of first-line therapy was 8.2 (3.4, 17.3) months. During the overall period between 2015 and 2021, the most common initial pharmacotherapy (88.1% of treatment regimens) was 'combined androgen blockade or androgen deprivation therapy only or first-generation anti-androgen only'. Use of androgen receptor signaling inhibitors increased following their introduction in 2018, reaching 26.6% of treatments started in 2021 (abiraterone + androgen deprivation therapy 9.4%, apalutamide + androgen deprivation therapy 9.2%, enzalutamide + androgen deprivation therapy 8.0%). Median total healthcare-related cost per person-year was JPY 244 479, with metastatic castration-sensitive prostate cancer drugs accounting for approximately one-third of the cost (JPY 396 620).

Conclusions: Since androgen receptor signaling inhibitors were introduced, treatment patterns in patients with metastatic castration-sensitive prostate cancer in Japan have shifted, with an increased trend toward prescription of these agents. However, the most frequently used regimen for first-line treatment continues to be 'combined androgen blockade or androgen deprivation therapy only or first-generation anti-androgen only'.

Introduction: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is a first-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, including both sensitizing and T790M resistance mutations. Its real-world efficacy against uncommon EGFR mutations remains under-researched.

Methods: The REIWA study, a multicentric, prospective, observational study conducted in Japan from September 2018 to August 2020, enrolled patients with advanced or recurrent EGFR mutation-positive NSCLC receiving osimertinib. Data on clinical outcomes, safety, disease progression, and subsequent treatments were collected for patients with uncommon EGFR mutations.

Results: Of 583 patients receiving osimertinib, 39 (6.7%) had an uncommon EGFR mutation. The present study included 32 of these patients after excluding seven patients with an exon 20 insertion mutation. The overall objective response rate was 53.1% [95% confidence interval (CI): 36.4-69.1], and the disease control rate was 78.1% (95% CI: 61.0-89.3). The median progression-free survival was 9.4 months (95% CI: 5.0-20.0), and the median overall survival (OS) was 21.8 (95% CI: 14.4-NA) months. Notably, patients with an exon21 L861Q mutation had a significantly longer OS than those with an exon18 G719X mutation, the respective values being 37.8 and 9.7 months (hazard ratio: 0.29; 95% CI: 0.10-0.85; P = 0.02). The rate of grade 3 or worse adverse events was 10.3%. Seven out of 32 (21.9%) patients showed progression involving only the central nervous system.

Conclusions: Osimertinib demonstrated efficacy and tolerability in the clinical setting in patients with uncommon EGFR mutation-positive NSCLC.

The standard approach for stage IV gastric cancer is palliative chemotherapy. However, despite the advancements in various chemotherapy regimens, the prognosis remains poor, highlighting the urgent need to develop more effective treatment strategies. The controversy persists regarding the integration of a local therapy including surgery in the management of unresectable stage IV gastric cancer. This randomized phase III trial aims to confirm the additional benefit of conversion surgery following palliative chemotherapy compared with palliative chemotherapy alone with respect to overall survival in patients initially diagnosed with unresectable clinical stage IVB or pathological stage IV gastric cancer after a remarkable response to chemotherapy. This study plans to enroll 126 patients from 63 institutions in Japan for 5 years, and it has been registered in the Japan Registry of Clinical Trials as jRCTs031240340 (https://jrct.niph.go.jp/latest-detail/jRCTs031240340).

Background: Osimertinib is effective in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC). However, some patients require osimertinib dose reduction because of adverse events. This study assessed the characteristics of osimertinib dose reduction and compared the efficacies of reduced-dose and regular-dose osimertinib.

Methods: This multicenter, prospective, observational study enrolled patients with EGFR mutation-positive NSCLC who started first-line osimertinib treatment between September 2018 and August 2020. We categorized the patients into two groups: those who required dose reduction during osimertinib treatment (reduction group) and those who continued osimertinib treatment at a dose of 80 mg/day without dose reduction (nonreduction group). The primary endpoints were progression-free survival (PFS) and pattern of progression, whereas the secondary endpoints included overall survival (OS) and reasons for osimertinib dose reduction.

Results: Of the included 575 patients, 175 (30.4%) and 400 (69.6%) were classified into the reduction and nonreduction groups, respectively. PFS was significantly better in the reduction group than in the nonreduction group [hazard ratio (HR) = 0.67, 95% confidence interval (CI) = 0.54-0.84; P <0.001]. Meanwhile, the pattern of progression and OS (HR = 0.82, 95% CI = 0.62-1.08; P = 0.15 ) did not differ significantly between the two groups. Osimertinib was reduced due to physician's decision or adverse events and the main reasons were rash and gastrointestinal symptoms such as nausea and diarrhea.

Conclusions: Many patients require osimertinib dose reduction due to adverse events, but this process does not adversely affect the drug efficacy.

Background: Intake of branched-chain amino acids (BCAA) has been suggested to have a prophylactic effect against carcinogenesis in colorectal cancer (CRC). However, the possible effect of plasma BCAA concentration has not been fully evaluated.

Methods: We conducted a prospective case-control study within a cohort of four public health center areas for which blood sample and questionnaire data from a 5-year follow-up survey were available. We identified 360 newly diagnosed CRC cases during the follow-up period and selected two matched controls for each case. We estimated odds ratio (OR) and 95% confidence intervals (CI) for CRC using conditional logistic regression models adjusted for potential confounding factors.

Results: Increased plasma concentrations of BCAAs were not inversely associated with CRC risk after adjustment for potential confounders. Compared with the lowest quartile, ORs in the highest quartile of leucine, isoleucine, valine, and total BCAA were 0.74 (95% CI, 0.49-1.12), 0.85 (0.56-1.29), 0.75 (0.50-1.13), and 0.70 (0.47-1.05), respectively. After excluding cases diagnosed within the first 6 years of follow-up, total BCAA and leucine were significantly related to a decreased risk of CRC, with ORs in the highest quartile of total BCAA and leucine of 0.58 (0.35-0.96) and 0.56 (0.33-0.93), respectively.

Conclusions: We found no statistically significant inverse association between plasma BCAA concentrations and CRC risk in overall analyses, whereas on 6-year exclusion, total BCAA and leucine were associated with decreased CRC risk. Plasma BCAA concentrations may play a prophylactic role in colorectal carcinogenesis, and further investigation is warranted.

Objectives: This study aimed to compare the surgical outcomes of simple hysterectomy with sentinel lymph node biopsy for low-risk endometrial cancer performed using the hinotori™ Surgical Robot System and the da Vinci® Xi system.

Materials and methods: We retrospectively analyzed the data of 234 patients who underwent simple hysterectomy with sentinel lymph node biopsy at Kagoshima University Hospital between January 2017 and June 2024. Amongst them, 20 patients underwent surgery using the hinotori™ Surgical Robot System and 214 using the da Vinci® Xi. Surgical factors, including operative time, cockpit/console time, blood loss and sentinel lymph node detection, were evaluated. Statistical analyses included chi-square and Wilcoxon tests, with significance set at P < 0.05.

Results: The median operative and cockpit/console times were comparable between the two systems. However, the time from roll-in to the start of cockpit/console surgery was significantly longer for the hinotori™ Surgical Robot System than for the da Vinci® Xi (P = 0.0039). No significant differences were observed for blood loss, length of hospital stay, or complication rates. The sentinel lymph node detection rates and number of sentinel lymph nodes resected were similar between the two systems, with metastatic sentinel lymph node rates of 6% in both groups.

Conclusion: Simple hysterectomy with sentinel lymph node biopsy performed using the hinotori™ Surgical Robot System demonstrated outcomes comparable with those using the da Vinci® Xi system, with no significant differences in key surgical factors. These results suggest that the hinotori™ Surgical Robot System is a viable alternative for minimally invasive surgery in low-risk endometrial cancer. Further studies with larger sample sizes are required to validate these findings.