International Journal of Clinical Oncology最新文献

{"title":"Predictors of early progressive disease and antitumor effects by metastatic site in renal cell carcinoma treated with ipilimumab plus nivolumab.","authors":"Keiichiro Mori, Takafumi Yanagisawa, Tatsushi Kawada, Satoshi Katayama, Ryoichi Maenosono, Takuya Tsujino, Takeshi Hashimoto, Yosuke Hirasawa, Lan Inoki, Shingo Toyoda, Takuhisa Nukaya, Kiyoshi Takahara, Wataru Fukuokaya, Fumihiko Urabe, Takehiro Iwata, Kensuke Bekku, Yoshio Ohno, Ryoichi Shiroki, Kazutoshi Fujita, Haruhito Azuma, Motoo Araki, Takahiro Kimura","doi":"10.1007/s10147-025-02878-z","DOIUrl":"https://doi.org/10.1007/s10147-025-02878-z","url":null,"abstract":"<p><strong>Background: </strong>Despite durable benefits of ipilimumab and nivolumab in metastatic renal cell carcinoma (mRCC), early progressive disease (PD), defined as disease progression within 3 months, occurs, and its predictors remain unclear. We aimed to investigate the clinical factors associated with early PD in patients with mRCC treated with this regimen.</p><p><strong>Methods: </strong>A retrospective analysis of a multi-institutional database identified 193 patients with mRCC treated with ipilimumab plus nivolumab. Logistic regression analyses assessed associations between clinical factors and early PD.</p><p><strong>Results: </strong>During a median follow-up of 17 months, patients had median overall (OS) and progression-free survival (PFS) of 35 and 14 months, respectively. Objective response and PD rates were 49.9% and 24.9%, respectively. Patients with early PD had significantly worse OS than those with non-early PD (10 vs. 42 months; P = 0.0002). Multivariate analyses identified bone metastasis and performance status (PS) as independent indicators of early PD (P = 0.03 and 0.01, respectively). Early PD rates varied by metastatic site (lung, 19.3%; bone, 31.2%; brain, 10%; and liver, 30%). Patients with clear-cell RCC had a median OS of 48 months and PFS of 22 months. The identified variables of early PD were consistent across all patient populations evaluated.</p><p><strong>Conclusions: </strong>Bone metastasis and PS predict early PD in patients with mRCC treated with ipilimumab plus nivolumab, with antitumor effect of the regimen varying by metastatic site. Clarifying the characteristics of early PD may guide clinical decision-making in treatment selection.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000571","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":"Music therapy preferences among breast cancer patients undergoing perioperative chemotherapy: from qualitative insight to quantitative evidence.","authors":"Nanami Nakaya, Ami Yamasato, Mayu Kondo, Shigeki Okino, Atsuko Kitano, Banri Tsuda, Makoto Tokuhara, Kenji Yamamoto","doi":"10.1007/s10147-025-02872-5","DOIUrl":"10.1007/s10147-025-02872-5","url":null,"abstract":"<p><strong>Background: </strong>Patients with breast cancer (PWBC) have a high risk of developing psychological disorders, and interventions should be implemented with care. For music therapy (MT) interventions to be more effective among these patients, providing therapeutic programs tailored to their preferences is desirable. Given the limited research on the preferences for MT of PWBC undergoing chemotherapy, we had previously conducted a qualitative study to clarify their preferences, yielding the formation of related hypotheses. Building upon these hypotheses, the current quantitative study aimed to clarify the specific preferences regarding MT of PWBC, who are undergoing chemotherapy, in Japan.</p><p><strong>Methods: </strong>This quantitative study's questionnaire was created based on the results of our prior qualitative study and completed by 300 PWBC undergoing perioperative chemotherapy.</p><p><strong>Results: </strong>(a) Of all participants, 80.9% wanted MT, and there was a relationship between preferred activity type and participants' sociodemographic and clinical characteristics; (b) the expectations of participants regarding MT differed by preferred activity type; and (c) the participants' preferences regarding the frequency, timing, duration, and cost of the MT intervention were constant regardless of the preferred activity type.</p><p><strong>Conclusions: </strong>As patients' specific preferences have been clarified, we conclude that professionals may be more well-positioned and informed to devise more appropriate and effective MT programs to be incorporated into the treatment schedules of PWBC who are undergoing chemotherapy, with vital quality-of-life implications resulting.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953139","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 talaporfin sodium photodynamic therapy as a salvage treatment for locally recurrent esophageal squamous cell carcinoma.","authors":"Mamoru Tanaka, Makiko Sasaki, Hirotada Nishie, Yuki Kojima, Yasunari Sasaki, Taketo Suzuki, Shigeki Fukusada, Naomi Sugimura, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka","doi":"10.1007/s10147-025-02864-5","DOIUrl":"https://doi.org/10.1007/s10147-025-02864-5","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) presents significant treatment challenges, with chemoradiotherapy (CRT) leading to local recurrence in 30-40% of cases. Limitations of traditional salvage therapies have driven interest in photodynamic therapy with talaporfin sodium (TS-PDT), a minimally invasive treatment with reduced phototoxicity, which has been increasingly utilized since its approval in Japan.</p><p><strong>Methods: </strong>This retrospective study at the Nagoya City University Hospital (May 2016-December 2023) assessed the efficacy of TS-PDT for esophageal cancer after CRT or radiotherapy in 29 patients who met specific inclusion criteria. The evaluated outcomes included adverse events, local complete response (L-CR), progression-free survival (PFS), and overall survival (OS).</p><p><strong>Results: </strong>Among the patients (23 men and 6 women; median age, 72 years), TS-PDT achieved an L-CR rate of 81.5% per patient and 87.8% per lesion, with a higher success rate against T1b lesions. The median local PFS was 44.1 months, and OS had not yet been reached, with a 1-year survival rate of 91.9%. The adverse events included esophageal strictures and perforations.</p><p><strong>Conclusion: </strong>TS-PDT is a potentially effective salvage treatment for ESCC, offering efficient local control and favorable survival outcomes. Despite some adverse events, its reduced phototoxicity and versatility make it a viable option, particularly for elderly patients. Further multicenter trials are warranted to validate its role in esophageal cancer management.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953218","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":"Long-term outcomes of venetoclax and ibrutinib in Japanese patients with relapsed/refractory mantle cell lymphoma.","authors":"Hideki Goto, Satoshi Ito, Masahiro Kizaki, Masaki Yamaguchi, Noriko Fukuhara, Koji Kato, Toko Saito, Yasuhito Terui, Tomomi Soshin, Natsuko Satomi-Tsushita, Hideyuki Honda, Chen Qian, Koji Izutsu","doi":"10.1007/s10147-025-02865-4","DOIUrl":"10.1007/s10147-025-02865-4","url":null,"abstract":"<p><strong>Background: </strong>Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) face a poor prognosis in the absence of effective treatment options. Ibrutinib plus venetoclax demonstrated high response rates and a tolerable safety profile in the primary analysis of the Phase 2, M20-075 study (NCT04477486) in Japanese patients with R/R MCL. We report updated efficacy and safety from this study with longer follow-up.</p><p><strong>Methods: </strong>Patients received 560 mg ibrutinib and 400 mg venetoclax (5-week ramp-up to 400 mg) once daily for up to 104 weeks followed by ibrutinib monotherapy. Primary endpoint was Independent Review Committee-assessed complete response (CR) rate. Secondary endpoints included overall response rate (ORR), duration of response (DOR), undetectable minimal residual disease (uMRD) in patients achieving CR, progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>After a median follow-up of 37.2 months, 13 patients had received ibrutinib plus venetoclax, 8 (62%) remained on ibrutinib monotherapy, and 9 (69%) completed 24 months of venetoclax. ORR was 83% (10/12 [per-protocol population]; all CR); median DOR was not reached. All 6 patients positive for MRD at baseline who achieved CR had uMRD. Median PFS and OS were not reached. Most frequent Grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (46%) and leukopenia (23%); one TEAE leading to treatment discontinuation was squamous cell carcinoma unrelated to treatment. There were no cases of tumor lysis syndrome or TEAEs leading to death.</p><p><strong>Conclusion: </strong>Long-term follow-up of ibrutinib plus venetoclax showed prolonged efficacy and a well-tolerated safety profile in Japanese patients with R/R MCL.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953174","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":"Neutrophil-to-lymphocyte ratio affects the impact of proton pump inhibitors on efficacy of immune checkpoint inhibitors in patients with non‑small-cell lung cancer.","authors":"Tomoki Hori, Kazuhiro Yamamoto, Takefumi Ito, Shigeki Ikushima, Tomohiro Omura, Ikuko Yano","doi":"10.1007/s10147-025-02859-2","DOIUrl":"https://doi.org/10.1007/s10147-025-02859-2","url":null,"abstract":"<p><strong>Background: </strong>The neutrophil-to-lymphocyte ratio (NLR) at the initiation of immune checkpoint inhibitor (ICI) therapy is a known predictor of prognosis. Proton pump inhibitors (PPIs) reportedly attenuate the therapeutic efficacy of ICIs. However, the attenuation effects are not consistently observed across all patients. This study aimed to evaluate whether NLR serves as a stratification factor to determine the impact of PPI on the efficacy of ICI.</p><p><strong>Methods: </strong>This retrospective study was conducted in patients with NSCLC treated with ICI monotherapy. Patients were stratified into two groups (higher NLR (≥ 4) and lower NLR (< 4)). PPI use was defined as the administration of PPIs within 30 days before or after ICI initiation. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS).</p><p><strong>Results: </strong>Among the 132 patients included, PPI users exhibited significantly shorter median PFS and OS than non-PPI users. In the higher NLR group (n = 61), PPI users had a markedly shorter PFS and OS than non-PPI users (median PFS: 1.6 vs. 8.2 months; p < 0.01, median OS: 3.3 vs. 19.6 months; p = 0.015). Conversely, in the lower NLR group (n = 71), no significant difference in PFS and OS was observed between PPI users and non-PPI users (median PFS: 2.8 vs. 7.3 months, p = 0.83, median OS: 17.6 vs. 24.4 months, p = 0.40).</p><p><strong>Conclusion: </strong>NLR may be a significant stratification factor for evaluating the impact of PPI on PFS and OS in patients with NSCLC undergoing ICI monotherapy.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953122","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":"Current and emerging systemic treatment options for malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma.","authors":"Shinji Miwa, Norio Yamamoto, Katsuhiro Hayashi, Yuta Taniguchi, Hirotaka Yonezawa, Sei Morinaga, Satoru Demura","doi":"10.1007/s10147-025-02712-6","DOIUrl":"10.1007/s10147-025-02712-6","url":null,"abstract":"<p><p>Undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous histiocytoma (MFH) is the second most common soft-tissue sarcoma. The standard treatment options for UPS/MFH include tumor excision with appropriate surgical margins, radiation therapy, and chemotherapy. Preferable clinical outcomes can be expected in patients with resectable disease, whereas the clinical outcomes in patients with metastatic disease are unsatisfactory despite multidisciplinary treatment. Although patients with metastatic diseases require chemotherapy, the response rate to conventional chemotherapy has been reported to be only 27-33% in previous reports. Systemic treatment is required to eliminate metastatic disease and improve clinical outcomes in patients with UPS/MFH. Recent clinical studies have investigated the optimal period of conventional chemotherapy and the efficacy of various combinations of anticancer agents. Furthermore, molecular targeted drugs and immune checkpoint inhibitors have shown superior outcomes compared to standard treatments for various types of malignancies. Therefore, these anticancer agents are considered as new treatment options for patients with UPS/MFH. Recent clinical trials have demonstrated the safety and efficacy of these agents in patients with soft-tissue sarcomas, including UPS/MFH. In particular, a high response rate to immune checkpoint inhibitors combined with doxorubicin has been reported in recent clinical trials; however, combination therapy needs to be assessed in a large number of patients with UPS/MFH. In this review article, recent clinical studies on the systemic treatment of UPS/MFH are discussed.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"1734-1742"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005209","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":"A perspective on patient-derived orthotopic xenograft (PDOX) mouse models for identification of novel and individualized treatment for sarcoma.","authors":"Takashi Higuchi, Kentaro Igarashi, Shinji Miwa, Hiroaki Kimura, Katsuhiro Hayashi, Satoru Demura, Sei Morinaga, Yohei Asano, Norio Yamamoto, Francis J Hornicek, Hiroyuki Tsuchiya, Robert M Hoffman","doi":"10.1007/s10147-025-02801-6","DOIUrl":"10.1007/s10147-025-02801-6","url":null,"abstract":"<p><p>Sarcomas, including osteosarcoma and soft tissue sarcoma, are heterogeneous and rare diseases with limited treatment options and a high metastatic potential. Despite advancements in immunotherapy and targeted therapies, many sarcoma patients have limited durable responses to these treatments. Therefore, individualized precision medicine and novel drug discovery are greatly needed. To address this unmet need, we have developed a patient-derived orthotopic xenograft (PDOX) mouse model of sarcomas using surgical orthotopic implantation. The PDOX models more accurately recapitulate the complex characteristics of human tumors compared to traditional subcutaneous xenografts. This enhanced fidelity is due to the preservation of the original tumor's histology and the accurate representation of the tumor microenvironment within the orthotopic implantation site. The present report summarizes our research group's experience with the sarcoma PDOX model and underscores its significant potential for identifying effective therapeutics. We have obtained numerous promising and unexpected results, including the identification of active chemotherapy drugs, novel drug combinations, and experimental therapeutics tailored to individual patients. In the current era of growing advancements in precision medicine, PDOX models offer a unique opportunity for developing individualized and innovative therapy specifically tailored to the individual needs of sarcoma patients.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"1707-1721"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258047","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":"Celecoxib has less aggravating effect on cisplatin-induced nephrotoxicity in comparison with non-selective cyclooxygenase inhibitors: a retrospective multi-institutional study.","authors":"Keisuke Okamoto, Yoshitaka Saito, Kenta Takahashi, Yoh Takekuma, Jun Sakakibara-Konishi, Katsuya Narumi, Mitsuru Sugawara, Masaki Kobayashi","doi":"10.1007/s10147-025-02810-5","DOIUrl":"10.1007/s10147-025-02810-5","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin (CDDP)-induced nephrotoxicity (CIN) is one of its most serious adverse effects. Although we previously demonstrated that celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, attenuates CIN in a basic study, there are no reports that have evaluated its clinical impact on CIN. Therefore, we aimed to determine the effect of celecoxib on CIN compared with that of non-selective COX inhibitors.</p><p><strong>Methods: </strong>Patients with lung cancer receiving CDDP (≥ 60 mg/m²)-containing regimens with regular administration of loxoprofen or naproxen (COX-1 group), or celecoxib were evaluated in this retrospective, multi-institutional study. The primary endpoint was the evaluation of CIN incidence in all treatment cycles between the groups. In addition, the variance in creatinine clearance (CCr) and the incidence of gastrointestinal adverse effects were evaluated.</p><p><strong>Results: </strong>CIN occurred in 24.2% of patients in the COX-1 group (n = 33) and 0% of those in the celecoxib group (n = 15) in all cycles, showing a significant difference (P = 0.04). In addition, the variance in CCr was significantly smaller in the celecoxib group than in the COX-1 group in all cycles, as well as at the primary endpoint (P = 0.02). However, there was no difference in the incidence of CIN or variance in CCr in the first cycle between the two groups. The incidences of nausea, vomiting, and anorexia were similar between the groups, implying a similar amount of oral hydration.</p><p><strong>Conclusion: </strong>These findings suggest that celecoxib is less aggravating on CIN than non-selective COX inhibitors.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"1757-1763"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575390","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 trends in the use and outcomes of novel androgen receptor signaling inhibitor therapy in patients with non-metastatic castration-resistant prostate cancer: a multicenter retrospective study.","authors":"Fumiya Yoneyama, Naoki Fujita, Yohei Kawashima, Masanao Shinohara, Ryuji Tabata, Ryuma Tanaka, Takuya Oishi, Hikari Miura, Kyo Togashi, Kazutaka Okita, Hirotaka Horiguchi, Toshikazu Tanaka, Daisuke Noro, Yuichiro Suzuki, Satoshi Sato, Chikara Ohyama, Shingo Hatakeyama","doi":"10.1007/s10147-025-02827-w","DOIUrl":"10.1007/s10147-025-02827-w","url":null,"abstract":"<p><strong>Background: </strong>Although three phase III trials demonstrated significant oncological benefits of novel androgen receptor signaling inhibitors (ARSIs) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC), trends in novel ARSI use have been sparsely documented. Moreover, the safety and oncological benefits of novel ARSIs in real-world nmCRPC settings remain unclear.</p><p><strong>Methods: </strong>This multicenter retrospective study evaluated 318 consecutive patients with nmCRPC treated between 2001 and 2024. Trends in the use of novel ARSIs were analyzed. Adverse events associated with novel ARSIs were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox proportional hazards regression analyses were conducted to evaluate the effects of novel ARSIs on metastasis-free survival (MFS) and overall survival (OS).</p><p><strong>Results: </strong>The median age and follow-up period after nmCRPC diagnosis were 77 years and 46 months, respectively. Of the 318 patients, 231 (73%) received novel ARSI treatment at some point during nmCRPC management. First-line use of novel ARSIs gradually increased following their initial approval for nmCRPC in 2014. The rate of first-line novel ARSI use was significantly higher in 2020-2024 than in 2014-2019 (68% vs. 33%, P < 0.001). The incidence rates of any-grade and grade ≥ 3 adverse events associated with novel ARSIs were 23% and 2.2%, respectively. After adjusting for confounding variables, novel ARSIs were independently and significantly associated with prolonged MFS and OS.</p><p><strong>Conclusions: </strong>Novel ARSIs have become a primary treatment strategy for nmCRPC in real-world settings, demonstrating both safety and significant oncological benefits.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"1858-1865"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583853","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":"Phase II study of afatinib for advanced non-small cell lung cancer with uncommon epidermal growth factor receptor mutations, including compound mutations detected by next-generation sequencing.","authors":"Nobuaki Mamesaya, Keita Mori, Haruki Kobayashi, Shota Omori, Ryo Ko, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Toshiaki Takahashi","doi":"10.1007/s10147-025-02826-x","DOIUrl":"10.1007/s10147-025-02826-x","url":null,"abstract":"<p><strong>Background: </strong>There are no prospective clinical data on the efficacy of afatinib in patients with non-small cell lung cancer (NSCLC) harboring various uncommon epidermal growth factor receptor (EGFR) mutations detected using next-generation sequencing. We aimed to report the efficacy and safety of afatinib in patients with NSCLC harboring uncommon EGFR mutations detected using next-generation sequencing.</p><p><strong>Methods: </strong>This was a prospective single-center single-arm phase II study. Patients with histologically confirmed metastatic or recurrent NSCLC harboring uncommon EGFR mutations, excluding exon 20 insertion and T790M mutations detected using next-generation sequencing, were eligible. Patients received oral afatinib (40 mg once daily). The primary endpoint was the objective response rate. The secondary endpoints were progression-free survival, overall survival, and safety.</p><p><strong>Results: </strong>Between August 2019 and September 2022, 17 patients were enrolled. The median age was 71 years (range, 59-80 years; 9 males). The uncommon mutations identified were G719X (n = 4; 24%), S768I (n = 3; 17.6%), and L861Q (n = 6; 35%), and 13 other rare EGFR mutations were detected in 10 patients. These mutations were identified as single or compound mutations. The objective response rate for all patients was 82.4%, median progression-free survival was 11.3 months, and median overall survival was 27.8 months. Grade 3 or higher adverse events were diarrhea (n = 5; 29%), paronychia (n = 2; 12%), and decreased appetite (n = 2; 12%). All adverse events were manageable, and there were no treatment-related deaths.</p><p><strong>Conclusions: </strong>Afatinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"1787-1796"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567402","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}