International Journal of Clinical Oncology最新文献

{"title":"Investigation of tumor mutation burden using the comprehensive genomic profiling data of vulvar and vaginal malignant tumors: an observational study using C-CAT database.","authors":"Manabu Seino, Shiori Sano, Yuta Gonai, Shota Horikawa, Fumihiro Nakamura, Yosuke Okui, Jun Matsukawa, Hirotsugu Sakaki, Norikazu Watanabe, Keiko Yamauchi, Tsuyoshi Ohta, Yuki Hoshi, Shuhei Suzuki, Masaaki Kawai, Satoru Nagase","doi":"10.1007/s10147-025-02730-4","DOIUrl":"https://doi.org/10.1007/s10147-025-02730-4","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to reveal the gene alteration and tumor mutation burden (TMB) statuses of vulvar and vaginal malignant tumors in Japan.</p><p><strong>Methods: </strong>We investigated the cancer genomic profiling (CGP) data of 79 patients with vulvar and vaginal cancers. These data were obtained from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT).</p><p><strong>Results: </strong>None of the patients had high microsatellite instability. Although 21.9% of the patients with vulvar and vaginal squamous cell carcinoma (SCC) had high TMB, those with other histological types did not. The top single-nucleotide variants (SNVs) in SCC were TERT, TP53, CDKN2A, KMT2D, and NOTCH1. The frequencies of ATRX and PBRM1 were significantly higher in TMB-high SCC than in non-TMB-high SCC.</p><p><strong>Conclusion: </strong>SCC of the vulva and vagina is expected to have high TMB, and gene alteration status differed between TMB-high and non-TMB-high groups.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanoma skin cancer statistics derived from 7442 Japanese patients: Japanese melanoma study.","authors":"Yasuhiro Fujisawa, Shusuke Yoshikawa, Tatsuya Takenouchi, Shoichiro Mori, Jun Asai, Hisashi Uhara, Yuki Ichigosaki, Taku Fujimura, Yoshiyuki Nakamura, Yasuhiro Nakamura, Fumitaka Ohno, Takeshi Fukumoto, Toshiyuki Ozawa, Kenjiro Namikawa, Satoru Sugihara, Toshihiko Hoashi, Takatoshi Shimauchi, Yu Sawada, Hiroaki Iwata, Taku Maeda, Takuya Miyagawa, Yoshitsugu Shibayama, Naohito Hatta, Akiko Kishi, Masashi Ishikawa, Hisao Kawahira, Norito Katoh, Ryuhei Okuyama","doi":"10.1007/s10147-025-02747-9","DOIUrl":"https://doi.org/10.1007/s10147-025-02747-9","url":null,"abstract":"<p><strong>Background: </strong>Malignant melanoma (MM) is a rare but aggressive cutaneous cancer, accounting for only 2% of skin cancers in Japan but nearly half of skin cancer-related deaths. While the global incidence of MM is rising, its epidemiology varies significantly by ethnicity and geographic region. In Japan, melanoma incidence remains lower than in Western countries, with acral lentiginous melanoma (ALM) being the most prevalent subtype. However, comprehensive epidemiological and clinical data remain limited.</p><p><strong>Methods: </strong>We analyzed data from 7442 Japanese melanoma patients collected between 2005 and 2022 through the Japanese Melanoma Study (JMS). Demographic, clinical, and survival data were evaluated, including subtype distribution, TNM staging, and treatment outcomes.</p><p><strong>Results: </strong>ALM was the most common subtype (40.8%), followed by superficial spreading melanoma (20.2%). Lymph node metastasis was observed in 28.6% of cases, and distant metastasis in 10.9%. The BRAF mutation rate was 27.2%, with significantly lower frequencies in ALM (8.5%) and mucosal melanoma (4.8%). Among Stage IV patients, those treated with both immune checkpoint inhibitors (ICIs) and BRAF(+ MEK) inhibitors demonstrated significantly improved survival compared to chemotherapy alone (P < 0.05). Adjuvant BRAF(+ MEK) inhibitor therapy also resulted in superior relapse-free survival compared to those who did not receive adjuvant therapy (P < 0.005).</p><p><strong>Conclusion: </strong>This study provides the largest dataset of Japanese melanoma patients to date, highlighting distinct epidemiological and clinical characteristics. Given their lower BRAF mutation rates and the limited efficacy of current ICI treatments, these findings emphasize the urgent need for optimize immunotherapy strategies in Japanese melanoma patients.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a comprehensive set of fact sheets for cancer predisposition genes for medical oncologists practicing cancer genome profiling.","authors":"Manami Matsukawa, Chikako Tomozawa, Yoshiaki Nakamura, Takao Fujisawa, Kaori Kimura, Yumie Hiraoka, Riu Yamashita, Shinji Kosugi, Akihiro Sakurai, Issei Imoto, Masakazu Nishigaki, Makoto Hirata, Takeshi Kuwata, Takayuki Yoshino","doi":"10.1007/s10147-025-02746-w","DOIUrl":"https://doi.org/10.1007/s10147-025-02746-w","url":null,"abstract":"<p><strong>Background: </strong>Comprehensive genomic profiling (CGP) is widely performed worldwide, increasing opportunities for medical oncologists to explain cancer predisposition at the time of informed consent and return of results. How medical oncologists communicate about (suspected) cancer predisposition genes is a key factor in referring patients for consultation with genetic services. In this study, we developed a set of fact sheets on cancer predisposition genes to support medical oncologists in their practice under the nationwide cancer genome screening project MONSTAR-SCREEN-2 study in Japan.</p><p><strong>Methods: </strong>The Genetic Specialist Committee, comprising clinical geneticists, genetic counselors, bioinformaticians, and medical oncologists, drafted the fact sheet and external Genetic Experts reviewed its elements and contents. A fact sheet evaluation survey was conducted one year after the fact sheet was completed and distributed to medical oncologists at the National Cancer Center Hospital East.</p><p><strong>Results: </strong>The content of the fact sheet included an overview of diseases, inheritance, family impact, lifetime risk, and surveillance. In the evaluation survey, 83.3% of respondents rated it as \"useful.\" Notably, the sections \"What is genetic counseling\" (100%) and \"Lifetime risk\" (94.4%) received high ratings.</p><p><strong>Conclusion: </strong>Our study suggests that a fact sheet developed by the Genetic Specialist Committee may help medical oncologists explain CGP results and connect patients to genetic services. It also functions as an educational resource that requires periodic updates and is in line with revisions to the guidelines.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum amylase level as a predictive biomarker for persistent grade 1 chemotherapy-associated oral mucositis: a retrospective cross-sectional study.","authors":"Nursema Ozdemir, Ali Alkan, Ozgur Tanriverdi","doi":"10.1007/s10147-025-02749-7","DOIUrl":"https://doi.org/10.1007/s10147-025-02749-7","url":null,"abstract":"<p><strong>Background: </strong>This study aims to determine the relationship between persistent grade 1 chemotherapy-related oral mucositis and serum amylase level.</p><p><strong>Methods: </strong>The study was conducted as a retrospective cross-sectional study. Among the patients diagnosed with cancer whose file information was available, the files of those whose chemotherapy-related oral mucositis status was recorded after the first cycle treatment were examined. Among these patients, those whose serum amylase levels were checked for any reason and those who did not meet the exclusion criteria were included in the study.</p><p><strong>Results: </strong>A total of 376 patients were analyzed. It was observed that grade 1 oral mucositis persisted in 44% of the patients. With the ROC curve, the cut-off value for serum amylase level before the second cycle treatment was determined to be 69.5 U/L (AUC 0.771, 95% CI 0.720-0.821, p = 0.00011). The sensitivity rate of serum amylase levels above this value in predicting chemotherapy-associated oral mucositis was 68.29% and the specificity rate was 100%. In univariate and multivariate logistic (binary) regression analysis, it was concluded that high serum amylase level was an independent factor affecting the presence of oral mucositis (OR 3.37, 95% CI 1.94-9.66; p = 0.00014).</p><p><strong>Conclusion: </strong>It was concluded that serum amylase level may be an independent predictive factor for determining persistent grade 1 chemotherapy-induced oral mucositis. Original.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of dose-dense chemotherapy for early-stage breast cancer under prophylactic pegfilgrastim administration: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022.","authors":"Takamichi Yokoe, Tetsuhiro Yoshinami, Kazuki Nozawa, Yukinori Ozaki, Hiroshi Nishio, Kenji Tsuchihashi, Eiki Ichihara, Yuji Miura, Makoto Endo, Shingo Yano, Dai Maruyama, Nobuyuki Susumu, Munetaka Takekuma, Takashi Motohashi, Mamoru Ito, Eishi Baba, Nobuaki Ochi, Toshio Kubo, Keita Uchino, Takahiro Kimura, Yutaro Kamiyama, Shinji Nakao, Shinobu Tamura, Hitomi Nishimoto, Yasuhisa Kato, Atsushi Sato, Toshimi Takano","doi":"10.1007/s10147-025-02716-2","DOIUrl":"10.1007/s10147-025-02716-2","url":null,"abstract":"<p><strong>Background: </strong>In early-stage breast cancer, dose-dense chemotherapy, which involves the administration of standard doses at shorter intervals, is safer when administered with granulocyte colony-stimulating factor (G-CSF) to mitigate chemotherapy-induced neutropenia. This study aimed to thoroughly evaluate the advantages and disadvantages of dose-dense regimens based on the use of G-CSF.</p><p><strong>Methods: </strong>A systematic review was conducted according to the \"Minds Handbook for Clinical Practice Guideline Development\" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing dose-dense chemotherapy with prophylactic pegfilgrastim administration in early-stage breast cancer were included. Outcomes included overall survival, event-free survival, incidence of febrile neutropenia, quality of life (QOL), and pain. Meta-analyses were performed on outcomes with sufficient data.</p><p><strong>Results: </strong>Our literature search identified 23 RCTs. Overall survival and event-free survival showed a trend favoring dose-dense therapy (hazard ratio, 0.90, 0.90; 95% confidence interval [CI] 0.78 - 1.03, 0.80 - 1.01; p = 0.13; 0.07, respectively). The incidence of febrile neutropenia was similar between the groups (odds ratio, 0.90; 95% CI 0.58 - 1.40; p = 0.65). Mortality due to infection could not be compared owing to the small number of events. Pain increased with dose-dense therapy (odds ratio 2.57; 95% CI 1.00 - 6.62; p = 0.05), likely from G-CSF-induced bone pain. Only one study examined QOL, showing a decline with chemotherapy that recovered after treatment.</p><p><strong>Conclusions: </strong>Dose-dense chemotherapy trended toward improved survival outcomes without increasing the risk of infection, although pain increased. Further research should identify the specific subgroups that most benefit from dose-dense regimens. More data are needed on the impact on QOL.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"674-683"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world outcomes with avelumab + axitinib in patients with advanced renal cell carcinoma in Japan: subgroup analyses from the J-DART2 study by International Metastatic Renal Cell Carcinoma Database Consortium risk classification.","authors":"Junya Furukawa, Taigo Kato, Toshinari Yamasaki, Keisuke Monji, Toshiaki Tanaka, Norihiko Tsuchiya, Tomoaki Miyagawa, Hiroshi Yaegashi, Tomoyasu Sano, Takashi Karashima, Kazutoshi Fujita, Jun-Ichi Hori, Takayuki Ito, Masahiro Kajita, Yoshihiko Tomita, Nobuo Shinohara, Masatoshi Eto, Mototsugu Oya, Hirotsugu Uemura","doi":"10.1007/s10147-024-02655-4","DOIUrl":"10.1007/s10147-024-02655-4","url":null,"abstract":"<p><strong>Background: </strong>Avelumab + axitinib was approved for the treatment of advanced renal cell carcinoma (aRCC) in Japan in December 2019. We report long-term real-world subgroup analyses with first-line avelumab + axitinib in patients with aRCC by International Metastatic RCC Database Consortium (IMDC) risk classification from the J-DART2 study in Japan.</p><p><strong>Methods: </strong>J-DART2 was a multicenter, noninterventional, retrospective study examining characteristics, treatment patterns, and outcomes in patients with aRCC who started first-line avelumab + axitinib in Japan between December 2019 and October 2022.</p><p><strong>Results: </strong>Data from 150 patients across 19 sites were analyzed. IMDC risk was favorable in 39 patients (26.0%), intermediate (1 risk factor) in 46 (30.7%), intermediate (2 risk factors) in 36 (24.0%), and poor in 29 (19.3%). Baseline characteristics were generally consistent across IMDC risk subgroups. In subgroups with favorable, intermediate (1 risk factor), intermediate (2 risk factors), and poor risk, median progression-free survival was 31.0, 15.3, 16.4, and 8.1 months; median overall survival (OS) was not reached, but 24-month OS rates were 95.2%, 91.3%, 85.3%, and 57.6%, respectively. Objective response rates were 54.5%, 56.8%, 47.1%, and 54.2%, respectively. High-dose corticosteroid treatment for immune-related adverse events was administered in 5.1%, 8.7%, 8.3%, and 6.9% of patients, respectively.</p><p><strong>Conclusion: </strong>Subgroup analyses from J-DART2 confirm the long-term real-world effectiveness of first-line avelumab + axitinib across IMDC risk groups in patients with aRCC in Japan. Our findings were consistent with previous analyses by IMDC risk and support the favorable benefit-risk profile of avelumab + axitinib in clinical practice in Japan.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"749-760"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective observational study on the relationships between genetic alterations and survival in Japanese patients with metastatic castration-sensitive prostate cancer: the impact of IDC-P.","authors":"Masashi Kato, Hiroyuki Sato, Yushi Naito, Akiyuki Yamamoto, Hideji Kawanishi, Yojiro Nakano, Toshinori Nishikimi, Masataka Kobayashi, Atsuya Kondo, Hiroki Hirabayashi, Satoshi Katsuno, Fumitoshi Sakamoto, Tohru Kimura, Shigeki Yamamoto, Hidemori Araki, Kosuke Tochigi, Fumihiro Ito, Hatsuro Hatsuse, Naoto Sassa, Akihiro Hirakawa, Shusuke Akamatsu, Toyonori Tsuzuki","doi":"10.1007/s10147-025-02707-3","DOIUrl":"10.1007/s10147-025-02707-3","url":null,"abstract":"<p><strong>Background: </strong>Intraductal Carcinoma of the Prostate (IDC-P) is a significant prognostic indicator for prostate cancer, which demonstrates significant associations with homologous recombination repair gene mutations (HRRm) and alterations in tumor suppressor genes. However, no study in Japan has investigated the association between IDC-P and genetic mutations in men with metastatic castration-sensitive prostate cancer (mCSPC).</p><p><strong>Methods: </strong>This prospective observational study enrolled 102 de novo mCSPC (LATITUDE high-risk) patients diagnosed between 2018 and 2021, with subsequent monitoring of survival outcomes. A single genitourinary pathologist evaluated all needle biopsy slides. Genetic analyses were performed using the Myriad myChoice HRD plus™. These genetic analyses covered 108 genetic loci, including 15 HRRm genes, with a success rate of 91%.</p><p><strong>Results: </strong>Genetic alterations were observed in 79 patients (77.5%), with 20 exhibiting HRRm (19.6%). Common genetic alterations included FOXA1 (29.4%) and TP53 (17.6%) mutations; BRCA (9.8%) mutations were the most frequent HRRm (BRCA1:2 cases, BRCA2:8 cases, including 6 biallelic). IDC-P-positive patients demonstrated a significantly higher frequency of genetic aberrations (82.6% vs. 50%, p = 0.0082). Patients with biallelic BRCA2, TP53, and PTEN mutations exhibited significantly poorer cancer-specific survival. Multivariate analysis identified lactate dehydrogenase (LDH) (HR 1.005, p = 0.035), TP53 mutations (HR 5.196, p < 0.001), biallelic BRCA2 mutations (HR 10.686, p = 0.005), and IDC-P as independent predictors of poor cancer-specific survival. No cancer-related deaths occurred in IDC-P-negative cases.</p><p><strong>Conclusion: </strong>Our study emphasizes the significant association between IDC-P and an elevated incidence of genetic alterations in Japanese mCSPC patients, emphasizing the need for early genetic testing to guide therapeutic decision-making.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"789-796"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of patients with metastatic renal cell carcinoma who do not respond to axitinib treatment.","authors":"Kojiro Ohba, Takahiro Osawa, Takahiro Kojima, Tomohiko Hara, Mikio Sugimoto, Masatoshi Eto, Keita Minami, Yasutomo Nakai, Kosuke Ueda, Sei Naito, Norio Nonomura, Sachiyo Murai, Hiroyuki Nishiyama, Hiromi Nakanishi, Yuta Mukae, Kensuke Mitsunari, Tomohiro Matsuo, Ryoichi Imamura, Nobuo Shinohara","doi":"10.1007/s10147-025-02715-3","DOIUrl":"10.1007/s10147-025-02715-3","url":null,"abstract":"<p><strong>Background: </strong>Axitinib is a widely used tyrosine kinase inhibitor (TKI) in metastatic renal cell carcinoma (mRCC) treatment. Here, we analyzed the characteristics of patients who did not respond to axitinib and evaluated alternative options for their treatment.</p><p><strong>Methods: </strong>We retrospectively analyzed data for 449 patients with mRCC who were administered axitinib following another TKI as initial therapy. Patients with progressive disease (PD) at their first assessment were defined as showing early-PD. We analyzed the characteristics of patients at risk of early-PD and evaluated the relationship between the treatment following axitinib and their prognosis.</p><p><strong>Results: </strong>Early-PD was diagnosed in 102 patients, and was more common in those who had not undergone nephrectomy (p < 0.001), those treated with a TKI for a short period (p < 0.001), and those in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) poor risk category for mRCC (p < 0.001). Multivariate analysis showed that these were independent risk factors for early-PD (all p < 0.001). Of those with early-PD, 52 changed to next-line treatment. The progression-free survival periods were 5.5 (95% confidence interval (CI) 2.4-8.6) months for patients administered TKIs, 4.2 (95% CI 0.3-8.1) months for those on nivolumab, and 2.2 (1.8-2.6) months for those on mammalian target of rapamycin inhibitors (p = 0.030).</p><p><strong>Conclusion: </strong>Patients who have not undergone nephrectomy, those previously treated with another TKI for a short period, and those in the IMDC poor risk category are more likely to experience early-PD when taking axitinib. Furthermore, TKIs are the best treatment for patients with early-PD who have previously been administered axitinib.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"781-788"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib enhances antitumor immunity of anti-PD-1 antibody.","authors":"Yu Kato","doi":"10.1007/s10147-025-02721-5","DOIUrl":"10.1007/s10147-025-02721-5","url":null,"abstract":"<p><p>Lenvatinib is an orally available multi-tyrosine kinase inhibitor that mainly targets vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling. These inhibitory activities of lenvatinib exhibit antitumor efficacy, mainly due to their repressive effects on angiogenesis. In addition, a recent non-clinical evaluation using mouse tumor models revealed that lenvatinib causes immunomodulatory effects, including activation of effector T-cells and regulation of tumor-associated macrophages (TAMs). Combined treatment with lenvatinib and anti-programmed cell death-1 antibody (anti-PD-1) resulted in enhanced antitumor activity relative to monotreatment with anti-PD-1 or lenvatinib. This review summarizes the antitumor mechanisms of lenvatinib and of lenvatinib plus anti-PD-1 combination therapy.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"666-673"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-marketing surveillance of encorafenib in combination with binimetinib in Japanese patients with BRAF-mutant melanoma.","authors":"Naoya Yamazaki, Hidenori Sakata, Osamu Iida, Teruaki Katayama, Hisashi Uhara","doi":"10.1007/s10147-025-02693-6","DOIUrl":"10.1007/s10147-025-02693-6","url":null,"abstract":"<p><strong>Background: </strong>A BRAF inhibitor, encorafenib, combined with a MEK inhibitor, binimetinib, was approved in Japan in early 2019 for the treatment of BRAF V600-mutant, unresectable malignant melanoma based on results of the global phase III trial, COLUMBUS, conducted in various countries including Japan. This post-marketing surveillance (PMS) assessed the combination in real-world clinical practice in Japan.</p><p><strong>Methods: </strong>We performed a prospective, multicentre, 12-month PMS of the safety and effectiveness of encorafenib plus binimetinib for radically unresectable, BRAF-mutant malignant melanoma in Japan.</p><p><strong>Results: </strong>Among 174 survey forms collected from 85 centres between February 2019 and August 2020, 172 were included for safety and effectiveness analysis. Patients (male [52.3%], median age 62.0 years) had Eastern Cooperative Oncology Group Performance Status 0 or 1 (91.8%) and comorbidities (55.2%). Respective encorafenib and binimetinib median dosages were 450 mg/day and 90 mg/day; median treatment duration, 24.1 and 24.2 weeks, and discontinuation, 71.5% for each, primarily for disease progression (56.9%) and adverse drug reactions (ADRs, 38.2%). Safety assessment ADRs occurred in 99 patients (57.6%), including eye disorders (40.7%), hepatic dysfunction (20.3%), rhabdomyolysis (4.7%), haemorrhage (2.3%), palmar-plantar erythrodysaesthesia syndrome (1.7%), and hypertension (1.7%); 19.8% were grade ≥ 3, none were grade 5, most resolved with/without treatment modification. At 12 months, the objective response rate was 48.8% (95% CI 41.2, 56.6; complete [19.2%], partial [29.7%]), overall survival was 40.1%.</p><p><strong>Conclusion: </strong>The safety and effectiveness of encorafenib plus binimetinib in Japanese patients with BRAF-mutant malignant melanoma were similar to data reported in COLUMBUS; no new safety concerns were identified.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"814-823"},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}