Therapeutic Advances in Medical Oncology最新文献

{"title":"Molecular features of NSCLC patients with liver metastasis.","authors":"Jun Zhao, Jia Zhong, Yujie Chen, Zipei Chen, Huan Yin, Yuange He, Rongrong Chen, Renhua Guo","doi":"10.1177/17588359241275421","DOIUrl":"https://doi.org/10.1177/17588359241275421","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is the primary cause of lung cancer-related death. Primary cancer cells invade through the lymphatic or blood vessels to distant sites. Recently, it was proposed that lymphatic metastasis was more a hallmark of tumor aggressiveness or metastatic potential than a gateway to metastases. Therefore, the underlying molecular mechanism of metastasis is not entirely clear.</p><p><strong>Objectives: </strong>This study aimed to explore the genetic mechanisms underlying liver metastases from lung cancer and to evaluate the efficacy of different therapies in these patients.</p><p><strong>Design: </strong>We retrospectively analyzed the mutation spectrum of different biopsy samples including primary lung tumors, liver, lymph node metastasis, and circulating tumor DNA (ctDNA) from 1090 non-small-cell lung cancer (NSCLC) patients with liver metastasis between the years 2017 and 2022.</p><p><strong>Methods: </strong>Demographic and disease characteristics were summarized using descriptive parameters. Time to treatment discontinuation was used to analyze the clinical outcome.</p><p><strong>Results: </strong>More liquid biopsies were performed than tissue biopsies, especially in the treated advanced NSCLC patients. Liver metastasis before treatment was associated with poor response to immune checkpoint inhibitors and targeted therapy. Liver and lymph node metastasis had higher levels of single nucleotide variants and copy number variants than primary lung tumors. In paired lung and liver, lymph nodes, and simultaneous ctDNA, we found actionable mutations were always shared, while metastasis samples had multiple private mutations. Serial ctDNA analysis identifies potential resistant mutations and describes the evolution of tumor cells.</p><p><strong>Conclusion: </strong>Liver and lymph node metastasis in NSCLC showed shared actionable mutations. Of note, the discrepancy of private mutations in liver and lymph node metastases indicated that liver metastases are mainly seeded by the primary tumor rather than the earlier colonized lymph node metastases.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241275421"},"PeriodicalIF":4.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of neoadjuvant chemotherapy response and prognosis among pegylated liposomal doxorubicin, epirubicin and pirarubicin in HR ⩽ 10%/HER2-negative breast cancer: an exploratory real-world multicentre cohort study.","authors":"Yue Hong, Jing Peng, Qitong Chen, Qin Zhou, Feng Xu, Jia Yao, Qiongyan Zou, Liqin Yuan, Lun Li, Qian Long, Liqiu Liao, Mingwen Liu, Xuan Liu, Danhua Zhang, Shouman Wang, Wenjun Yi","doi":"10.1177/17588359241279695","DOIUrl":"https://doi.org/10.1177/17588359241279695","url":null,"abstract":"<p><strong>Background: </strong>Pegylated liposomal doxorubicin (PLD), epirubicin and pirarubicin are the main anthracyclines widely used in China. PLD demonstrates therapeutic response comparable to epirubicin and pirarubicin in neoadjuvant chemotherapy (NAC) of breast cancer.</p><p><strong>Objectives: </strong>The objectives of our study were to retrospectively assess the real-world effectiveness and prognostic characteristics of PLD as NAC for HR ⩽ 10%/human epidermal growth factor receptor 2 (HER2)-negative breast cancer.</p><p><strong>Design: </strong>This was a retrospective study.</p><p><strong>Methods: </strong>Our study enrolled patients with HR ⩽ 10%/HER2-negative breast cancer who received PLD-, epirubicin- or pirarubicin-based NAC from three centres in Hunan Province, China, between 2015 and 2022. We employed inverse probability of treatment weighting to balance the differences in patients' characteristics among the PLD, epirubicin, and pirarubicin groups. The endpoints were pathological complete response (pCR), event-free survival (EFS), and overall survival (OS).</p><p><strong>Results: </strong>A total of 267 patients were included. After NAC, the pCR rates in PLD group were superior to epirubicin group (PLD, 34.1%; epirubicin, 20.8%, <i>p</i> = 0.038). The differences in EFS (log-rank <i>p</i> = 0.99) and OS (log-rank <i>p</i> = 0.33) among the three groups were not statistically significant. Among the three groups, non-pCR patients had worse EFS than pCR patients (log-rank <i>p</i> = 0.014). For patients with pCR, the differences in EFS (log-rank <i>p</i> = 0.47) and OS (log-rank <i>p</i> = 0.38) were not statistically significant among the three groups, and the EFS (log-rank <i>p</i> = 0.59) and OS (log-rank <i>p</i> = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups.</p><p><strong>Conclusion: </strong>PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241279695"},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival predictors in patients with pancreatic cancer on liposomal irinotecan plus fluorouracil/leucovorin: a multicenter observational study.","authors":"Jiyoung Keum, Hee Seung Lee, Chan Su Park, Jeehoon Kim, Wonjoon Jang, Kyung In Shin, Huapyong Kang, Sang Hoon Lee, Jung Hyun Jo, Sung Ill Jang, Moon Jae Chung, Jeong Youp Park, Seung Woo Park, Jae Hee Cho, Seungmin Bang","doi":"10.1177/17588359241279688","DOIUrl":"https://doi.org/10.1177/17588359241279688","url":null,"abstract":"<p><strong>Background: </strong>Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure.</p><p><strong>Objectives: </strong>We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC.</p><p><strong>Design: </strong>Multicenter, retrospective cohort study.</p><p><strong>Methods: </strong>This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes.</p><p><strong>Results: </strong>Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0-8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9-3.2). An albumin level of<4.0 g/dL, neutrophil-to-lymphocyte ratio (NLR) of ⩾3.5, liver or peritoneal metastasis, and a history of >3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, <i>p</i> = 0.388; PFS: 3.6 vs 2.6 months, <i>p</i> = 0.126).</p><p><strong>Conclusion: </strong>An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241279688"},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody drug conjugates in recurrent or metastatic cervical cancer: a focus on tisotumab vedotin state of art.","authors":"Floriana Camarda, Mariachiara Paderno, Maria Chiara Cannizzaro, Camilla Nero, Ilaria Sabatucci, Giovanni Fucà, Lucia Musacchio, Vanda Salutari, Giovanni Scambia, Domenica Lorusso","doi":"10.1177/17588359241277647","DOIUrl":"https://doi.org/10.1177/17588359241277647","url":null,"abstract":"<p><p>Cervical cancer (CC) is still characterized by a poor prognosis despite the progress made in its treatment in recent years. Although immunotherapy has improved outcomes for advanced/recurrent disease, there is a significant gap in addressing patients' needs when they progress after platinum and immunotherapy treatments. In this setting, traditional chemotherapy showed limited effectiveness. In this context, antibody-drug conjugates (ADCs) emerged as a promising tool within targeted cancer therapies. Tisotumab vedotin (TV), an ADC targeting tissue factor, represents the first ADC approved by the US Food and Drug Administration for the treatment of recurrent or metastatic CC with disease progression on or after chemotherapy. In phase I-III published trials, TV has already demonstrated an advantage in terms of objective response rate (17.8%-54.4%) and progression-free survival (3.1-6.9 months) in patients who progressed to the first-line standard therapy. Data concerning the addition of TV to platinum/pembrolizumab first-line chemotherapy are still under analysis and strongly expected. However, several questions are still unresolved: (1) the identification of the most suitable timing for ADCs administration in the treatment sequence of advanced/recurrent CC; (2) the evaluation of combination therapies as a tool to minimize the emergence of resistant clones and to enhance overall effectiveness; and (3) the assessment of tolerability and correct management of special toxicities (e.g. ocular and neurological adverse events). In the near future, an improvement in patient selection via biomarker-driven strategies should be crucial for optimizing both treatment benefits and maintaining an acceptable toxicity profile.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241277647"},"PeriodicalIF":4.3,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of carboplatin-etoposide rechallenge after first-line chemo-immunotherapy in ES-SCLC: an international multicentric analysis.","authors":"Igor Gomez-Randulfe, Sofía Silva Díaz, Carles Escriu, Saara Mohammed, Riyaz Shah, Javier David Benitez Fuentes, Samantha Cox, Federico Monaca, Emilio Bria, María Rosario García-Campelo, Benjamin Crook, Toby Talbot, Rita Leporati, Kirsty Balachandran, Tom Newsom-Davis, Sarah Hughes, Laura Cove-Smith, Paul Taylor, Fiona Blackhall, Raffaele Califano","doi":"10.1177/17588359241272957","DOIUrl":"10.1177/17588359241272957","url":null,"abstract":"<p><strong>Background and objectives: </strong>Second-line treatment for small-cell lung cancer (SCLC) is primarily guided by the time elapsed since the last platinum dose. Rechallenge with carboplatin and etoposide has demonstrated superior outcomes compared to topotecan if the platinum-free interval (PFI) is longer than 90 days and is considered the standard of care. However, these findings predate the chemo-immunotherapy era. This study investigates the effectiveness of the rechallenge strategy after chemo-immunotherapy in a real-world setting.</p><p><strong>Design and methods: </strong>We retrospectively reviewed patients with the extensive stage (ES)-SCLC who received rechallenge with carboplatin and etoposide after first-line chemoimmunotherapy between September 2020 and August 2023 in nine European centres. Demographic and clinical data were collected and analysed.</p><p><strong>Results: </strong>A total of 93 patients were included. Sixty-six (71%) patients had a PFI between 3 and 6 months. Consolidation thoracic radiotherapy and prophylactic cranial irradiation had been administered in 31 (33.3%) patients and 20 (21.5%) patients, respectively. Overall response rate was 59.1%. Median progression-free survival (PFS) was 5 months (95% confidence interval (CI) 4.3-5.7) and median overall survival (OS) was 7 months (95% CI 5.7-8.3). Notably, PFS and OS were not different according to PFI (3-6 m vs > 6 m).</p><p><strong>Conclusion: </strong>Rechallenge with carboplatin and etoposide is a valid second-line option in patients with ES-SCLC whose disease progresses after first-line chemoimmunotherapy. Our analysis shows similar results to previous studies. Furthermore, outcomes were consistent across patients with different PFIs, confirming its efficacy in patients with a PFI longer than 3 months.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241272957"},"PeriodicalIF":4.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness analysis of durvalumab plus tremelimumab as first-line therapy in patients with unresectable hepatocellular carcinoma.","authors":"Weiting Liao, Huiqiong Xu, David Hutton, Qiuji Wu, Yang Yang, Mingyang Feng, Wanting Lei, Liangliang Bai, Junying Li, Qiu Li","doi":"10.1177/17588359241274625","DOIUrl":"https://doi.org/10.1177/17588359241274625","url":null,"abstract":"<p><strong>Background: </strong>The HIMALAYA trial found that durvalumab plus tremelimumab significantly prolonged progression-free survival and overall survival in patients with unresectable hepatocellular carcinoma (HCC) compared with sorafenib.</p><p><strong>Objective: </strong>This study aimed to investigate the cost-effectiveness of durvalumab plus tremelimumab compared with sorafenib in the first-line HCC setting.</p><p><strong>Design: </strong>A Markov model-based cost-effectiveness analysis.</p><p><strong>Methods: </strong>We created a Markov model to compare healthcare costs and clinical outcomes of HCC patients treated with durvalumab plus tremelimumab in the first-line setting compared with sorafenib. We estimated transition probabilities from randomized trials. Lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated for first-line durvalumab plus tremelimumab compared with sorafenib from a US payer's perspective.</p><p><strong>Results: </strong>In the base case, first-line durvalumab plus tremelimumab was associated with an improvement of 0.29 QALYs compared with sorafenib. While both treatment strategies were associated with considerable lifetime expenditures, first-line durvalumab plus tremelimumab was less expensive than sorafenib ($188,405 vs $218,584). The incremental net monetary benefit for durvalumab plus tremelimumab versus sorafenib was $72,762 (valuing QALYs at $150,000 each). The results of durvalumab plus tremelimumab were better in terms of costs and health outcomes in patients with HBV-related HCC and high alpha-fetoprotein levels.</p><p><strong>Conclusion: </strong>First-line durvalumab plus tremelimumab was estimated to be dominant for the treatment of unresectable HCC compared with sorafenib from a US payer's perspective.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241274625"},"PeriodicalIF":4.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastatic perirectal PEComa treated by checkpoint inhibitor immunotherapy and multimodal treatment: case report and review of the literature.","authors":"Maxime Rémond, Atanas Pachev, Maxime Battistella, Camille Gandon, Samia Mourah, Isabelle Madelaine, Léon Maggiori, Bethsabée Benadon, Nassim Hammoudi, Nelson Lourenço, Thomas Aparicio","doi":"10.1177/17588359241280541","DOIUrl":"10.1177/17588359241280541","url":null,"abstract":"<p><p>Malignant PEComas are an extremely rare subtype of soft tissue sarcomas. Here, we report the case of a man presenting with a perirectal PEComa and liver metastasis. Since the tumor harbored a tumor mutational burden of 23/Mb and a programmed death-ligand 1 tumor positivity score of 50%, the patient was treated with pembrolizumab as a second line of systemic therapy, in combination with everolimus. This combined therapy led to a near-complete response of the primary tumor and a partial response of the metastasis. Radioembolization of the liver metastasis was performed due to isolated liver progression, and the pelvic tumor was treated by radiotherapy because of pelvic symptoms. The disease is still stable after 13 months of pembrolizumab plus everolimus and multimodal treatment. This case shows that malignant PEComas can display molecular features associated with sensitivity to checkpoint inhibitors. The use of checkpoint inhibitors may be a relevant therapeutic strategy in these patients. It is also the first report on selective internal radiation therapy in PEComas.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241280541"},"PeriodicalIF":4.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting mTOR signaling for the treatment of intrahepatic cholangiocarcinoma with TSC1/ARID1A mutations: a case report with an unexpected response.","authors":"Clémentine Daugan,Romain Boidot,François Ghiringhelli,Christophe Borg,Angélique Vienot","doi":"10.1177/17588359241271793","DOIUrl":"https://doi.org/10.1177/17588359241271793","url":null,"abstract":"Biliary tract cancer incidence is increasing and the prognostic remains dismal. The development of personalized medicine is a pivotal issue in proposing therapeutic options for biliary tract cancer patients. Whole exome sequencing identifies approximately 15% of IDH1 mutations and 15% of FGFR2 fusions in intrahepatic cholangiocarcinoma. Other patients are not currently eligible for targeted therapy. Here, we present a patient treated for a metastatic cholangiocarcinoma with an unexpected response to a mammalian target of rapamycin (mTOR) targeting agent. Whole exome sequencing enabled the identification of TSC1 and ARID1A mutations. Reintroduction of mTOR inhibitors with similar results sustains the main role of these targeted agents in the control of the disease. These results suggest the existence of an mTOR oncogenic addiction in biliary tract cancer. Our results support the interest in performing exome sequencing in liver cancers and the potential to identify actionable mutations with important therapeutic issues.","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"197 1","pages":"17588359241271793"},"PeriodicalIF":4.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, safety, and efficacy of an alternative dosing regimen of sasanlimab in participants with advanced NSCLC and other malignancies.","authors":"Konstantin Penkov,Igor Bondarenko,Daria Viktorovna Saenko,Yaroslav Kulyaba,Jun Guo,Yi Gong,Noboru Yamamoto,Yevhen Stepanovych Hotko,Vasyl Boyko,Natalya Vladimirovna Fadeeva,Grygorii Mykolaiovych Ursol,Hee Kyung Ahn,Nikolay Viktorovich Kislov,Chia-I Shen,Craig Davis,Karey Kowalski,Elisabete Michelon,Dmitri Pavlov,Tomoko Hirohashi,Byoung Chul Cho","doi":"10.1177/17588359241274592","DOIUrl":"https://doi.org/10.1177/17588359241274592","url":null,"abstract":"BackgroundSasanlimab (PF-06801591), a humanized immunoglobulin G4 monoclonal antibody, binds to programmed cell death protein-1 (PD-1), preventing ligand (PD-L1) interaction.ObjectivesTo evaluate pharmacokinetics (PK), safety, tolerability, and efficacy of two subcutaneous sasanlimab dosing regimens.DesignAn open-label study consisting of phases Ib and II. Phase Ib: non-randomized, dose escalation, and expansion study in Asian participants with advanced malignancies.Phase IIconducted globally in participants with non-small-cell lung cancer with PD-L1 positive or PD-L1 status unknown tumors; participants were randomized 1:2 to receive subcutaneous sasanlimab 300 mg once every 4 weeks (300 mg-Q4W) or 600 mg once every 6 weeks (600 mg-Q6W).MethodsPrimary endpoint in phase Ib: dose-limiting toxicity (DLT) occurring in first treatment cycle; in phase II: C trough and AUC.ResultsA total of 155 participants (phase Ib, n = 34; phase II, n = 121) received sasanlimab. Phase Ib: no DLT reported. Phase II: ratio of adjusted geometric mean for AUCtau was 231.2 (90% CI, 190.1-281.2) and C trough was 111.5 (90% CI, 86.3-144.0) following 600 mg-Q6W (test) versus 300 mg-Q4W (reference). Phase Ib: grade 3 treatment-related adverse events (TRAEs) occurred in 1/4 (25%) and 3/12 (25%) participants treated in 300 mg-Q4W dose escalation and expansion cohorts, respectively. Phase II: grade 3 TRAEs occurred in 3/41 (7.3%) and 3/80 (3.8%) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively; no grade 4/5 TRAEs. Phase II: confirmed objective response was observed in 11/41 (26.8% (95% CI, 14.2-42.9)) and 12/80 (15.0% (95% CI, 8.0-24.7)) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively.ConclusionsPhase Ib regimens were considered safe with no DLTs reported. In phase II, 600 mg-Q6W regimen criteria were met for AUCtau and C trough metrics to support PK-based extrapolation of efficacy of alternative regimen. Regimens were well tolerated, showing anti-tumor activity in participants with advanced solid tumors. Administration of sasanlimab at a dose of 600 mg-Q6W subcutaneously may serve as a convenient alternative to 300 mg-Q4W administration.Trial registrationNCT04181788 (ClinicalTrials.gov); 2019-003818-14 (EudraCT).","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"24 1","pages":"17588359241274592"},"PeriodicalIF":4.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing treatment efficacy: combined therapy of eribulin, anlotinib, and camrelizumab in advanced or metastatic retroperitoneal liposarcoma.","authors":"Weiwei Jia,Jianhui Wu,Hongtao Zhang,Yan Wu,Daoning Liu,Zhen Wang,Xiaopeng Wang,Chengpeng Li,Chunyi Hao","doi":"10.1177/17588359241276968","DOIUrl":"https://doi.org/10.1177/17588359241276968","url":null,"abstract":"BackgroundRetroperitoneal liposarcoma (RLPS) typically shows limited response to standard chemotherapy, presenting a challenge in treating advanced or metastatic RLPS.ObjectiveThis study aimed to evaluate the potential advantages of a combined therapeutic strategy utilizing eribulin, anlotinib, and camrelizumab.DesignBetween December 2020 and March 2023, this retrospective study enrolled patients with advanced or metastatic RLPS who received treatment at Peking University Cancer Hospital Sarcoma Center. The treatment regimen involved eribulin plus anlotinib and camrelizumab administered every 3 weeks (Q3W).MethodsEfficacy was assessed following the Response Evaluation Criteria in Solid Tumors version 1.1, while safety was evaluated using the Common Terminology Criteria for Adverse Events version 5.0.ResultsThe study included 47 patients with RLPS with a median age of 55.5 years. Patients received a median of 4.5 (range, 2-21) cycles of treatment. Notably, partial response was observed in 8 patients (18.2%), while 25 (56.8%) exhibited stable disease. The objective response rate (ORR) and disease control rate were 18.2% and 75%, respectively. Significant differences in ORR were observed among histological subtypes (well-differentiated vs de-differentiated vs myxoid: 0 vs 17.9% vs 50%; p = 0.039). Six patients underwent surgery before disease progression, and one patient with myxoid liposarcoma (MLPS) had a pathological complete response. With a median follow-up of 21.8 (range, 2.7-30.7) months, the median progression-free survival (mPFS) was 6.9 (95% confidence interval (CI), 4.7-9.1) months, and the 6-month PFS rate was 60.5%. Based on various histological subtypes, the mPFS was 8.4 (95% CI, 4.1-12.7) months with well-differentiated liposarcoma, 5.8 (95% CI, 3.3-8.3) months with de-differentiated liposarcoma and not reached with MLPS, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 36 (76.6%) patients, with grade 3 or higher TRAEs in 21 (44.7%) patients. The most common TRAEs were neutropenia (53.2%), proteinuria (21.3%), and anorexia (21.3%).ConclusionThe combined treatment strategy involving eribulin, anlotinib, and camrelizumab showed promising efficacy and manageable safety in patients with advanced or metastatic RLPS, particularly in those with MLPS.","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"3 1","pages":"17588359241276968"},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}