MedPub Date : 2025-05-09DOI: 10.1016/j.medj.2025.100674
Enrico Heffler, Giovanni Paoletti
{"title":"Depemokimab in chronic rhinosinusitis with nasal polyps: A turning point or a missed opportunity?","authors":"Enrico Heffler, Giovanni Paoletti","doi":"10.1016/j.medj.2025.100674","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100674","url":null,"abstract":"<p><p>The ANCHOR-1 and ANCHOR-2 trials of the long-acting anti-interleukin (IL)-5 monoclonal antibody depemokibab in chronic rhinosinusitis with nasal polyposis demonstrated the safety and statistical efficacy of the drug compared to placebo.<sup>1</sup> However, its clinical benefits appear limited compared to other biologic therapies. The reduced dosing interval may improve adherence, but further research is needed to identify the most responsive patients.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 5","pages":"100674"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-05-09Epub Date: 2025-04-28DOI: 10.1016/j.medj.2025.100675
Jeanette Bresson Ladegaard Knox, Mie Seest Dam, Sara Green, Daniel E Stange, Franziska Baenke, Bon-Kyoung Koo, Steffen Rulands, Tim Schmäche, Vivian Mittné, Ivan Terlizzi, Beatrix Jahnke, Mette N Svendsen
{"title":"Navigating ethical challenges across professions: Insights from an Ethics Lab on patient-derived organoids.","authors":"Jeanette Bresson Ladegaard Knox, Mie Seest Dam, Sara Green, Daniel E Stange, Franziska Baenke, Bon-Kyoung Koo, Steffen Rulands, Tim Schmäche, Vivian Mittné, Ivan Terlizzi, Beatrix Jahnke, Mette N Svendsen","doi":"10.1016/j.medj.2025.100675","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100675","url":null,"abstract":"<p><p>In translational medicine, ethics is often treated as a question of approval and something to overcome to be allowed to do research. Given the many moral challenges related to developing biomedicine, we argue for the need to expand our understanding of ethics.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 5","pages":"100675"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-05-09DOI: 10.1016/j.medj.2024.100571
Li-Ping Ge, Yi-Zhou Jiang
{"title":"Combination of autophagy inhibitors with high-dose CDK4/6 inhibitors offers new hope for advanced HR+/HER2- breast cancer.","authors":"Li-Ping Ge, Yi-Zhou Jiang","doi":"10.1016/j.medj.2024.100571","DOIUrl":"https://doi.org/10.1016/j.medj.2024.100571","url":null,"abstract":"<p><p>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) with endocrine therapy are standard for advanced hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. However, treatment options following resistance to CDK4/6is remain poorly defined. Gong et al. conducted a phase 1b/2 trial, demonstrating that autophagy inhibitors combined with high-dose CDK4/6is are well tolerated and effective in patients with advanced HR+/HER2- breast cancer resistant to first-line CDK4/6i therapy.<sup>1</sup>.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 5","pages":"100571"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-05-09Epub Date: 2024-12-19DOI: 10.1016/j.medj.2024.11.009
Daniel Wiese, Hyuna Sung, Ahmedin Jemal, Farhad Islami
{"title":"Progress in reducing mortality from 10 major causes by county poverty level, from 1990-1994 to 2016-2020, in the US.","authors":"Daniel Wiese, Hyuna Sung, Ahmedin Jemal, Farhad Islami","doi":"10.1016/j.medj.2024.11.009","DOIUrl":"10.1016/j.medj.2024.11.009","url":null,"abstract":"<p><strong>Background: </strong>Overall death rates in the US have been declining in the past few decades. However, progress against mortality across counties with different socioeconomic profiles has not been well described. The objective of this study was to examine changes in death rates from leading causes of death by county poverty level in the contiguous US.</p><p><strong>Methods: </strong>Using county-level death (all causes, 10 leading causes in 2020, excluding COVID-19) and population data derived from the National Center for Health Statistics, we calculated absolute and relative changes in age-standardized death rates by county poverty level from 1990-1994 to 2016-2020.</p><p><strong>Findings: </strong>From 1990-1994 to 2016-2020, death rates from all causes, diseases of the heart, cancer, cerebrovascular disease, and pneumonia/influenza declined nationally, but rates increased for unintentional injury, chronic obstructive pulmonary disease, Alzheimer's disease, diabetes, suicide/self-inflicted injury, and kidney disease mortality. Counties with higher poverty levels (≥20%) had smaller declines or larger increases in death rates for each evaluated cause of death, exacerbating the disparities in mortality by county poverty level, except for unintentional injury and suicide/self-inflicted injury. Consequently, in 2016-2020, the death rates for leading causes of death were 12% (for Alzheimer's disease; suicide/self-inflicted injury) to 81% (for diabetes) higher in people residing in counties with the highest poverty level than in those residing in counties with the lowest poverty level.</p><p><strong>Conclusions: </strong>Disparities in mortality from most leading causes of death by county poverty level widened during the past three decades.</p><p><strong>Funding: </strong>There was no external funding for this study.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100556"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Audiological characteristics following gene therapy in patients with autosomal recessive deafness 9.","authors":"Longlong Zhang, Dingding Dong, Yanbo Yin, Honghai Tang, Jun Lv, Qi Cao, Wuqing Wang, Bing Chen, Yunfeng Wang, Huawei Li, Daqi Wang, Yilai Shu","doi":"10.1016/j.medj.2025.100696","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100696","url":null,"abstract":"<p><strong>Background: </strong>Gene therapy shows promising potential for patients with autosomal recessive deafness 9 (DFNB9), with ongoing clinical trials (ChiCTR2200063181). A deeper understanding of changes in audiological characteristics is crucial for optimizing the monitoring and evaluation of patients' recovery post-treatment.</p><p><strong>Methods: </strong>Audiological data were collected from 10 DFNB9 patients who underwent gene therapy, including auditory brain stem response (ABR), auditory steady-state response (ASSR), distortion product otoacoustic emission (DPOAE), and pure-tone audiometry (PTA) tests.</p><p><strong>Findings: </strong>A clear ABR wave V was observed in all participants by 13 weeks. By 52 weeks, distinct ABR waves I and III were visible in some participants. The 1-kHz ABR wave V latency at 85 dB decreased significantly from 9.220 (range 9.015-9.810) ms at 4 weeks to 8.190 (range 7.780-8.530) ms at 52 weeks (p = 0.004), with a trend toward increased wave V amplitude (p = 0.055). Significant correlations were observed between PTA, ABR, and ASSR thresholds at 0.5-4 kHz. The DPOAE signal-to-noise ratio (SNR) at 26 weeks post-treatment showed no significant difference compared with pre-treatment SNR values, nor were there significant correlations between the pre-treatment SNR values and the post-treatment ABR thresholds.</p><p><strong>Conclusions: </strong>The study demonstrates that ABR and ASSR are reliable objective tools for assessing hearing recovery in DFNB9 patients after gene therapy. ABR reveals positive changes in the auditory pathway over time after gene therapy, enhancing our understanding of the impact of gene therapy on auditory pathway recovery.</p><p><strong>Funding: </strong>This work was funded by the National Natural Science Foundation of China.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100696"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-05-09Epub Date: 2024-12-27DOI: 10.1016/j.medj.2024.11.012
Chang Gong, Qun Lin, Tao Qin, Yinduo Zeng, Fei Xu, Yaping Yang, Dong Yin, Zhuxi Duan, Chun-Long Chen, Louis Wing-Cheong Chow, Qiang Liu, Ahmed Hamaï, Maryam Mehrpour, Qianchong Lin, Jun Li, Erwei Song
{"title":"Targeting autophagy plus high-dose CDK4/6 inhibitors in advanced HR+HER2- breast cancer: A phase 1b/2 trial.","authors":"Chang Gong, Qun Lin, Tao Qin, Yinduo Zeng, Fei Xu, Yaping Yang, Dong Yin, Zhuxi Duan, Chun-Long Chen, Louis Wing-Cheong Chow, Qiang Liu, Ahmed Hamaï, Maryam Mehrpour, Qianchong Lin, Jun Li, Erwei Song","doi":"10.1016/j.medj.2024.11.012","DOIUrl":"10.1016/j.medj.2024.11.012","url":null,"abstract":"<p><strong>Background: </strong>The unmet needs of managing patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer who progress after cyclin-dependent kinase (CDK)4/6 inhibitor (CDK4/6i) treatment remain unclarified.</p><p><strong>Methods: </strong>This was a phase 1b/2, single-arm, open-label study that enrolled 29 patients with HR+/HER2- breast cancer who experienced first-line palbociclib treatment failure. The primary endpoint was the incidence of dose-limiting toxicity (DLT). The secondary endpoints were the objective response rate (ORR) and progression-free survival (PFS). The clinical trial registration number is ClinicalTrials.gov: NCT05953350.</p><p><strong>Findings: </strong>The phase 1b study demonstrated no DLT in patients treated with hydroxychloroquine (HCQ; 600 mg, bis in die [bid]) plus increasing doses of palbociclib (100, 150, or 200 mg, quaque die [qd]). The plasma pharmacokinetics of palbociclib were not significantly affected by HCQ. The recommended phase 2 dose (RP2D) was HCQ (600 mg, bid) plus palbociclib (200 mg, qd). The dose-expansion cohort demonstrated that HCQ plus palbociclib (200 mg, qd) treatment was tolerable. Grade 3 treatment-emergent adverse events (TEAEs) with an incidence higher than 15.0% included neutropenia (25.0%), leukopenia (25.0%), fatigue (20.0%), and back pain (15.0%). The ORR of all enrolled patients in our present trial was 41.4% (12/29). In the dose-expansion cohort, with the last enrolled patient having a follow-up duration of 32.3 weeks, the median PFS was not reached. The clinical benefit rate (CBR) at 6 months was 90.0% (95% confidence interval [CI]: 68.3%-98.8%). These findings were supported by preclinical data.</p><p><strong>Conclusions: </strong>Combined HCQ with high-dose CDK4/6i palbociclib (200 mg, qd) showed tolerable toxicity and promising efficacy for patients with advanced HR+/HER2- breast cancer after CDK4/6i failure.</p><p><strong>Funding: </strong>This work was funded by the National Natural Science Foundation of China.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100559"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-05-09DOI: 10.1016/j.medj.2025.100693
Jiatong Ding, Yue Yu, Dandan Cui, Shujun Xing, Dawei Wu, Yuan Fang, Ning Jiang, Peiwen Ma, Yale Jiang, Dongyan Liu, Weijie Yu, Yanjie Han, Jiawei Zhou, Hong Fang, Shuopeng Jia, Qiyu Tang, Shuhang Wang, Ning Li
{"title":"Learning from the LEAP trial series: Optimizing clinical trial design for combination therapies.","authors":"Jiatong Ding, Yue Yu, Dandan Cui, Shujun Xing, Dawei Wu, Yuan Fang, Ning Jiang, Peiwen Ma, Yale Jiang, Dongyan Liu, Weijie Yu, Yanjie Han, Jiawei Zhou, Hong Fang, Shuopeng Jia, Qiyu Tang, Shuhang Wang, Ning Li","doi":"10.1016/j.medj.2025.100693","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100693","url":null,"abstract":"<p><p>The LEAP trial series examining the synergy of pembrolizumab and lenvatinib across various cancers has yielded mixed results, highlighting the need for a more detailed understanding of combination therapies. By learning from these trials, we aim to advance the clinical development of more effective combination strategies to improve patient outcomes.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 5","pages":"100693"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-05-09Epub Date: 2024-12-30DOI: 10.1016/j.medj.2024.11.019
Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Katja Palm, Carlos E Prada, Takuo Kubota, Paul Arundel, Yumiko Kotani, Antonio Leiva-Gea, Michael B Bober, Jacqueline T Hecht, Janet M Legare, Sue Lawrinson, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan R S Day
{"title":"Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.","authors":"Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Katja Palm, Carlos E Prada, Takuo Kubota, Paul Arundel, Yumiko Kotani, Antonio Leiva-Gea, Michael B Bober, Jacqueline T Hecht, Janet M Legare, Sue Lawrinson, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan R S Day","doi":"10.1016/j.medj.2024.11.019","DOIUrl":"10.1016/j.medj.2024.11.019","url":null,"abstract":"<p><strong>Background: </strong>Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.</p><p><strong>Methods: </strong>After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.gov: NCT03197766), participants were eligible to continue treatment in an open-label extension (ClinicalTrials.gov: NCT03424018) wherein all received 15 μg/kg vosoritide daily. Data from the CLARITY achondroplasia study provided an external untreated control population and reference data.</p><p><strong>Findings: </strong>The population comprised 119 participants. Annualized growth velocity with vosoritide was similar to the average-stature population before puberty. The mean (SD) differences in annualized growth velocity across each integer age (6-16 years) between treated and untreated children were 1.84 (0.38) cm/year in boys and 1.44 (0.63) cm/year in girls. Three-year comparisons of treated versus untreated children demonstrated an additional height gain of 5.75 cm (95% confidence interval [CI]: 4.93, 6.57) with vosoritide. A significant improvement in upper-to-lower body segment ratio at 3 years of treatment was observed for participants with assessments at age <11 (females) and <12 years (males) versus population-level, age-matched, untreated controls (p = 0.0087). The arm span-to-standing height ratio remained consistent with untreated participants. Vosoritide had a favorable safety profile with continuous treatment for up to 6 years (464.05 person years of exposure). No long-term harms or deaths were observed.</p><p><strong>Conclusions: </strong>Vosoritide treatment was well tolerated and had sustained growth-promoting effects in children with achondroplasia treated for up to 6 years.</p><p><strong>Funding: </strong>This work was funded by BioMarin Pharmaceutical.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100566"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-05-09Epub Date: 2024-12-30DOI: 10.1016/j.medj.2024.11.018
Ran Nir-Paz, Hadil Onallah, Michal Dekel, Yechiel N Gellman, Amir Haze, Ronen Ben-Ami, Ron Braunstein, Ronen Hazan, Danna Dror, Yonatan Oster, Meir Cherniak, Fabienne Attal, Ana Raquel Barbosa, Helena Dordio, Alexandra Wagner, Daniela Jones-Dias, José Neves, Margarida Barreto, Clara Leandro, Sofia Côrte-Real, Miguel Garcia
{"title":"Randomized double-blind study on safety and tolerability of TP-102 phage cocktail in patients with infected and non-infected diabetic foot ulcers.","authors":"Ran Nir-Paz, Hadil Onallah, Michal Dekel, Yechiel N Gellman, Amir Haze, Ronen Ben-Ami, Ron Braunstein, Ronen Hazan, Danna Dror, Yonatan Oster, Meir Cherniak, Fabienne Attal, Ana Raquel Barbosa, Helena Dordio, Alexandra Wagner, Daniela Jones-Dias, José Neves, Margarida Barreto, Clara Leandro, Sofia Côrte-Real, Miguel Garcia","doi":"10.1016/j.medj.2024.11.018","DOIUrl":"10.1016/j.medj.2024.11.018","url":null,"abstract":"<p><strong>Background: </strong>Phage therapy offers a promising alternative for treating serious infections, including diabetic foot ulcers (DFUs), through the lytic action of phages. This randomized double-blind study was conducted to evaluate the safety and tolerability of the TP-102 bacteriophage cocktail in patients with DFUs non-infected and infected with Staphylococcus aureus, Pseudomonas aeruginosa, and/or Acinetobacter baumannii.</p><p><strong>Methods: </strong>Nineteen participants with DFUs were randomized after susceptibility testing. TP-102 was applied topically at 10⁹ plaque-forming units (PFUs)/mL/cm³ to the target ulcer: 1 week for non-infected DFUs and 28 days for infected DFUs (PEDIS grade 2/3). The study was conducted in Israel.</p><p><strong>Findings: </strong>Main outcomes included the incidence and severity of TP-102-related adverse events, microbiological data, and ulcer healing. Thirteen patients received TP-102. No treatment-related adverse events were reported. Although the study was underpowered to determine the superiority of TP-102 over placebo, a greater proportion of patients in the TP-102 + standard of care (SOC) group showed microbiological reduction of target bacteria (t = 26) compared to the placebo + SOC group (80% versus 50%, p = 1.000). Additionally, a higher proportion of TP-102 patients reached 50% and 75% wound closure compared to placebo (5/7 [71.4%] versus 1/3 [33.3%], p = 0.500 and 2/7 [28.6%] versus none, p = 1.000, respectively). One patient in the TP-102 group achieved wound closure.</p><p><strong>Conclusions: </strong>TP-102 was well tolerated and safe, showing potential as a groundbreaking treatment in this field. Further studies are needed to confirm its safety and efficacy in larger populations with diabetic foot infections (ClinicalTrials.gov: NCT04803708).</p><p><strong>Funding: </strong>None to declare.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100565"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-05-09Epub Date: 2025-01-18DOI: 10.1016/j.medj.2024.100573
Huayi Li, Yu Xu, Xiaofei Jiao, Qin Xu, Zikun Peng, Ying Tang, Jieqing Zhang, Bowen Huang, Yiyang Shen, Baoping Chang, Bairong Xia, Wei Duan, Danbo Wang, Lijing Zhu, Ruifang An, Guonan Zhang, Yaling Tang, Jianli Huang, Hui Qiu, Li Wang, Yi Huang, Guiling Li, Jianhua Qian, Li Sun, Hong Zheng, Ge Lou, Youzhong Zhang, Youguo Chen, Liqin Lu, Yan Cheng, Jihong Liu, Weidong Zhao, Jianghai Ji, Aiqin He, Ke Wang, Guohua Yu, Hong Zhu, Cailing Ma, Jianlin Yuan, Xia Wang, Hongfei Zhang, Xinyan Ma, Chujun Cai, Kang Yin, Han Xie, Ya Wang, Shuyan Wang, Li Li, Hui Zhou, Jing Wang, Jianqing Zhu, Ding Ma, Qinglei Gao
{"title":"IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.","authors":"Huayi Li, Yu Xu, Xiaofei Jiao, Qin Xu, Zikun Peng, Ying Tang, Jieqing Zhang, Bowen Huang, Yiyang Shen, Baoping Chang, Bairong Xia, Wei Duan, Danbo Wang, Lijing Zhu, Ruifang An, Guonan Zhang, Yaling Tang, Jianli Huang, Hui Qiu, Li Wang, Yi Huang, Guiling Li, Jianhua Qian, Li Sun, Hong Zheng, Ge Lou, Youzhong Zhang, Youguo Chen, Liqin Lu, Yan Cheng, Jihong Liu, Weidong Zhao, Jianghai Ji, Aiqin He, Ke Wang, Guohua Yu, Hong Zhu, Cailing Ma, Jianlin Yuan, Xia Wang, Hongfei Zhang, Xinyan Ma, Chujun Cai, Kang Yin, Han Xie, Ya Wang, Shuyan Wang, Li Li, Hui Zhou, Jing Wang, Jianqing Zhu, Ding Ma, Qinglei Gao","doi":"10.1016/j.medj.2024.100573","DOIUrl":"10.1016/j.medj.2024.100573","url":null,"abstract":"<p><strong>Background: </strong>It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone. The primary endpoint was the objective response rate (ORR). Pivotal secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Findings: </strong>205 patients were randomized to receive IBI310-sintilimab (n = 103) or placebo-sintilimab (n = 102). The ORR difference between the IBI310-sintilimab arm (32.3%, 95% confidence interval [CI]: 23.3%-42.5%) and the placebo-sintilimab arm (23.5%, 95% CI: 15.5%-33.1%) was not significant (p = 0.17). IBI310-sintilimab and placebo-sintilimab exhibited median PFS values of 3.6 (95% CI: 2.7-6.3) and 4.2 months (95% CI: 2.8-6.2), respectively (hazard ratio [HR] = 0.91, 95% CI: 0.65-1.27; p = 0.58). The median OSs were 13.9 months (95% CI: 11.5-25.6) in the IBI310-sintilimab arm and 17.2 months (95% CI: 13.7-25.9) in the placebo-sintilimab arm (HR = 1.12, 95% CI: 0.79-1.58; p = 0.54). Adding IBI310 to sintilimab increased the incidence of grade ≥3 treatment-related adverse events (55% versus 19%).</p><p><strong>Conclusions: </strong>Compared to single-agent PD-1/PD-L1 blockade, dual blockade of CTLA-4 and PD-1/PD-L1 did not significantly improve clinical outcomes in R/M CC.</p><p><strong>Funding: </strong>This work was funded by Innovent Biologics (Suzhou).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100573"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}