Pub Date : 2024-11-14DOI: 10.1001/jamaoncol.2024.5145
Tonny Studsgaard Petersen, Kristian Karstoft, Freja Karuna Hemmingsen Sørup, Marie Lund, Allan Cramer
This cohort study investigates the regulatory fate in the European Union for drugs that received accelerated approval for cancer indications in the US.
这项队列研究调查了在美国获得癌症适应症加速审批的药物在欧盟的监管命运。
{"title":"Regulatory Fate of Cancer Indications in the European Union After Accelerated Approval in the US","authors":"Tonny Studsgaard Petersen, Kristian Karstoft, Freja Karuna Hemmingsen Sørup, Marie Lund, Allan Cramer","doi":"10.1001/jamaoncol.2024.5145","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5145","url":null,"abstract":"This cohort study investigates the regulatory fate in the European Union for drugs that received accelerated approval for cancer indications in the US.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"24 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImportancePatients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs.ObjectiveTo evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.Design, Setting, and ParticipantsThis multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China. Eligible patients had histologically or cytologically confirmed ES-SCLC without previous systemic antitumor therapy for ES-SCLC. Data were analyzed between May 6, 2023, and June 1, 2024.InterventionsPatients were randomized (1:1) to receive toripalimab, 240 mg, or placebo plus EP every 3 weeks for up to 4 to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxic effects, or up to 2 years of treatment.Main Outcomes and MeasuresThe primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS). Whole-exome sequencing results identified correlative biomarkers for clinical efficacy.ResultsAmong 595 screened patients, 442 eligible patients were randomized (median [range] age, 63 [30-77] years; 366 [82.8%] male); 223 patients were randomized to toripalimab plus EP, and 219 to placebo plus EP. By April 20, 2023, the median (range) survival follow-up was 13.7 (0.0-42.7) months. Compared with placebo, toripalimab improved investigator-assessed PFS (hazard ratio [HR], 0.67 [95% CI, 0.54-0.82]; <jats:italic>P</jats:italic> &lt; .001), and significantly reduced the risk of death (HR, 0.80 [95% CI, 0.65-0.98]; <jats:italic>P</jats:italic> = .03). The median OS was 14.6 (95% CI, 12.9-16.6) months in the toripalimab group vs 13.3 (95% CI, 11.8-14.4) months in the placebo group. Whole-exome sequencing results from 300 patients identified low intratumor heterogeneity, <jats:italic>HLA-A11<jats:sup>+</jats:sup> HLA-B62</jats:italic><jats:sup>−</jats:sup> haplotype, wild-type <jats:italic>KMT2D</jats:italic> and <jats:italic>COL4A4</jats:italic>, or sequence variations in <jats:italic>CTNNA2 or SCN4A</jats:italic> correlated with favorable PFS and OS in the toripalimab group. No new safety signals were observed. Grade 3 or higher treatment-emergent adverse event incidence was similar between the toripalimab and placebo safety set groups (199 of 222 patients [89.6%] vs 193 of 216 patients [89.4%], respectively).Conclusions and RelevanceIn this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in PFS and OS for patients with ES-SCLC. The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xl
{"title":"Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer","authors":"Ying Cheng, Wei Zhang, Lin Wu, Caicun Zhou, Donglin Wang, Bing Xia, Minghong Bi, Xiuhua Fu, Chong Li, Dongqing Lv, Yanqiu Zhao, Gongyan Chen, Tienan Yi, Jianan Huang, Min Li, Runxiang Yang, Xiaoping Huang, Ye Wang, Mingjun Zhang, Yueyin Pan, Yilan Sun, Sheng Hu, Xiqin Zhang, Min Zhou, Jian Fang, Faguang Jin, Yunpeng Liu, Yinyin Li, Zhihong Zhang, Jie Hu, Laiyu Liu, Rui Wang, Yan Li, Kangsheng Gu, Cuimin Ding, Qingxia Fan, Guojun Zhang, Yongxing Chen, Liyan Jiang, Wei-E. Zheng, Shaoshui Chen, Cheng Huang, Zhigang Han, Hong Yang, Jianfang Wang, Baocheng Wang, Huita Wu, Yongxing Bao, Manxiang Li, Xianming Luo, Shanshan Gu, Wenbo Yu, Kai Xu, Simo Zhang, Jianjun Yu","doi":"10.1001/jamaoncol.2024.5019","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5019","url":null,"abstract":"ImportancePatients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs.ObjectiveTo evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.Design, Setting, and ParticipantsThis multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China. Eligible patients had histologically or cytologically confirmed ES-SCLC without previous systemic antitumor therapy for ES-SCLC. Data were analyzed between May 6, 2023, and June 1, 2024.InterventionsPatients were randomized (1:1) to receive toripalimab, 240 mg, or placebo plus EP every 3 weeks for up to 4 to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxic effects, or up to 2 years of treatment.Main Outcomes and MeasuresThe primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS). Whole-exome sequencing results identified correlative biomarkers for clinical efficacy.ResultsAmong 595 screened patients, 442 eligible patients were randomized (median [range] age, 63 [30-77] years; 366 [82.8%] male); 223 patients were randomized to toripalimab plus EP, and 219 to placebo plus EP. By April 20, 2023, the median (range) survival follow-up was 13.7 (0.0-42.7) months. Compared with placebo, toripalimab improved investigator-assessed PFS (hazard ratio [HR], 0.67 [95% CI, 0.54-0.82]; <jats:italic>P</jats:italic> &amp;lt; .001), and significantly reduced the risk of death (HR, 0.80 [95% CI, 0.65-0.98]; <jats:italic>P</jats:italic> = .03). The median OS was 14.6 (95% CI, 12.9-16.6) months in the toripalimab group vs 13.3 (95% CI, 11.8-14.4) months in the placebo group. Whole-exome sequencing results from 300 patients identified low intratumor heterogeneity, <jats:italic>HLA-A11<jats:sup>+</jats:sup> HLA-B62</jats:italic><jats:sup>−</jats:sup> haplotype, wild-type <jats:italic>KMT2D</jats:italic> and <jats:italic>COL4A4</jats:italic>, or sequence variations in <jats:italic>CTNNA2 or SCN4A</jats:italic> correlated with favorable PFS and OS in the toripalimab group. No new safety signals were observed. Grade 3 or higher treatment-emergent adverse event incidence was similar between the toripalimab and placebo safety set groups (199 of 222 patients [89.6%] vs 193 of 216 patients [89.4%], respectively).Conclusions and RelevanceIn this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in PFS and OS for patients with ES-SCLC. The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xl","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"36 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14DOI: 10.1001/jamaoncol.2024.5032
Parsa Erfani, Ruth L. Okediji, Vivienne Mulema, Edward R. Scheffer Cliff, Kwanele Asante-Shongwe, Brittany L. Bychkovksy, Temidayo Fadelu
ImportanceLimited availability and affordability of cancer drugs contribute to staggering disparities in cancer survival between high-income and low- and middle-income countries (LMICs). As infrastructure for cancer care rapidly develops, there is an urgent need to reduce prices and improve access to cancer medicines in LMICs to advance pharmacoequity globally.ObservationsPrior strategies to expand access to cancer medicines in LMICs have primarily relied on charity or differential pricing and have yielded limited results. Policymakers at the World Health Assembly recently proposed several strategies to increase global access to cancer drugs. Reviewing empirical data and lessons learned from medication access programs for HIV, COVID-19, and other infectious diseases, 3 strategies that multilateral organizations can use to reduce prices of cancer drugs in LMICs are discussed herein. These include (1) building regional technology transfer and manufacturing hubs, (2) expanding and streamlining use of compulsory licenses, and (3) implementing global standards for drug price transparency. Counterpoints to the critiques of these policies are critiqued and how programs can use these strategies to build on existing disease-centered initiatives is discussed.Conclusions and RelevanceLessons learned from the global response to HIV and COVID-19 show that international collaboration and support from the World Health and Trade Organizations can ensure a unified, coordinated agenda for advancing access to care in LMICs. Building on these lessons and implementing similar approaches for cancer drugs can play a critical role in expanding accessibility and affordability of cancer medicines in LMICs. With a growing burden of cancer morbidity and mortality in LMICs, redoubled efforts to deliver essential cancer medications to LMICs would have an immense impact on global cancer control and achieving the United Nations Sustainable Development Goals.
{"title":"Advancing Global Pharmacoequity in Oncology","authors":"Parsa Erfani, Ruth L. Okediji, Vivienne Mulema, Edward R. Scheffer Cliff, Kwanele Asante-Shongwe, Brittany L. Bychkovksy, Temidayo Fadelu","doi":"10.1001/jamaoncol.2024.5032","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5032","url":null,"abstract":"ImportanceLimited availability and affordability of cancer drugs contribute to staggering disparities in cancer survival between high-income and low- and middle-income countries (LMICs). As infrastructure for cancer care rapidly develops, there is an urgent need to reduce prices and improve access to cancer medicines in LMICs to advance pharmacoequity globally.ObservationsPrior strategies to expand access to cancer medicines in LMICs have primarily relied on charity or differential pricing and have yielded limited results. Policymakers at the World Health Assembly recently proposed several strategies to increase global access to cancer drugs. Reviewing empirical data and lessons learned from medication access programs for HIV, COVID-19, and other infectious diseases, 3 strategies that multilateral organizations can use to reduce prices of cancer drugs in LMICs are discussed herein. These include (1) building regional technology transfer and manufacturing hubs, (2) expanding and streamlining use of compulsory licenses, and (3) implementing global standards for drug price transparency. Counterpoints to the critiques of these policies are critiqued and how programs can use these strategies to build on existing disease-centered initiatives is discussed.Conclusions and RelevanceLessons learned from the global response to HIV and COVID-19 show that international collaboration and support from the World Health and Trade Organizations can ensure a unified, coordinated agenda for advancing access to care in LMICs. Building on these lessons and implementing similar approaches for cancer drugs can play a critical role in expanding accessibility and affordability of cancer medicines in LMICs. With a growing burden of cancer morbidity and mortality in LMICs, redoubled efforts to deliver essential cancer medications to LMICs would have an immense impact on global cancer control and achieving the United Nations Sustainable Development Goals.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"37 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1001/jamaoncol.2024.4397
Joseph M. Unger, Cathee Till, Catherine M. Tangen, Dawn L. Hershman, Phyllis J. Goodman, Michael LeBlanc, William E. Barlow, Riha Vaidya, Lori M. Minasian, Howard L. Parnes, Ian M. Thompson
ImportanceDue to the often indolent nature of prostate cancer (PCA), treatment decisions must weigh the risks and benefits of cancer control with those of treatment-associated morbidities.ObjectiveTo characterize long-term treatment-related adverse effects and complications in patients treated for PCA compared to a general population of older males.Design, Setting, and ParticipantsThis cohort study used a novel approach linking data from 2 large PCA prevention clinical trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin-E Cancer Prevention Trial) with Medicare claims records. This analysis included patients with PCA who had been treated with prostatectomy or radiotherapy compared with an untreated control group. Multivariable Cox regression was used, with a time-varying covariate for the occurrence of PCA treatment, adjusted for age, race, and year of time-at-risk initiation, and stratified by study and intervention arm. Data analyses were performed from September 21, 2022, to March 18, 2024.ExposureProstatectomy and radiotherapy occurring after a PCA diagnosis, identified from trial data or Medicare claims records.Main Outcomes and MeasuresTen potential PCA treatment-related complications identified from Medicare claims data.ResultsThe study sample comprised 29 196 participants (mean [SD] age at time-at-risk initiation, 68.7 [4.8] years). Of these, 3946 participants had PCA, among whom 655 were treated with prostatectomy and 1056 with radiotherapy. The 12-year hazard risk of urinary or sexual complications was 7.23 times greater for those with prostatectomy (95% CI, 5.96-8.78; P &lt; .001) and 2.76 times greater for radiotherapy (95% CI, 2.26-3.37; P &lt; .001) compared to untreated participants. Moreover, among participants treated with radiotherapy, there was a nearly 3-fold greater hazard risk of bladder cancer than in the untreated (hazard ratio [HR], 2.78; 95% CI, 1.92-4.02; P &lt; .001), as well as an approximately 100-fold increased hazard risk of radiation-specific outcomes including radiation cystitis (HR, 131.47; 95% CI, 52.48-329.35; P &lt; .001) and radiation proctitis (HR, 87.91; 95% CI, 48.12-160.61; P &lt; .001). The incidence per 1000 person-years of any 1 of the 10 treatment-related complications was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.Conclusions and RelevanceThis cohort study found that, even after accounting for age-related symptoms and disease, PCA treatment was associated with higher rates of complications in the 12 years after treatment. Given the uncertain benefit of PCA treatment for most patients, these findings highlight the importance of patient counseling before PCA screening and treatment and provide a rationale for pursuing opportunities for cancer prevention.
{"title":"Long-Term Adverse Effects and Complications After Prostate Cancer Treatment","authors":"Joseph M. Unger, Cathee Till, Catherine M. Tangen, Dawn L. Hershman, Phyllis J. Goodman, Michael LeBlanc, William E. Barlow, Riha Vaidya, Lori M. Minasian, Howard L. Parnes, Ian M. Thompson","doi":"10.1001/jamaoncol.2024.4397","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4397","url":null,"abstract":"ImportanceDue to the often indolent nature of prostate cancer (PCA), treatment decisions must weigh the risks and benefits of cancer control with those of treatment-associated morbidities.ObjectiveTo characterize long-term treatment-related adverse effects and complications in patients treated for PCA compared to a general population of older males.Design, Setting, and ParticipantsThis cohort study used a novel approach linking data from 2 large PCA prevention clinical trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin-E Cancer Prevention Trial) with Medicare claims records. This analysis included patients with PCA who had been treated with prostatectomy or radiotherapy compared with an untreated control group. Multivariable Cox regression was used, with a time-varying covariate for the occurrence of PCA treatment, adjusted for age, race, and year of time-at-risk initiation, and stratified by study and intervention arm. Data analyses were performed from September 21, 2022, to March 18, 2024.ExposureProstatectomy and radiotherapy occurring after a PCA diagnosis, identified from trial data or Medicare claims records.Main Outcomes and MeasuresTen potential PCA treatment-related complications identified from Medicare claims data.ResultsThe study sample comprised 29 196 participants (mean [SD] age at time-at-risk initiation, 68.7 [4.8] years). Of these, 3946 participants had PCA, among whom 655 were treated with prostatectomy and 1056 with radiotherapy. The 12-year hazard risk of urinary or sexual complications was 7.23 times greater for those with prostatectomy (95% CI, 5.96-8.78; <jats:italic>P </jats:italic>&amp;lt; .001) and 2.76 times greater for radiotherapy (95% CI, 2.26-3.37; <jats:italic>P </jats:italic>&amp;lt; .001) compared to untreated participants. Moreover, among participants treated with radiotherapy, there was a nearly 3-fold greater hazard risk of bladder cancer than in the untreated (hazard ratio [HR], 2.78; 95% CI, 1.92-4.02; <jats:italic>P </jats:italic>&amp;lt; .001), as well as an approximately 100-fold increased hazard risk of radiation-specific outcomes including radiation cystitis (HR, 131.47; 95% CI, 52.48-329.35; <jats:italic>P </jats:italic>&amp;lt; .001) and radiation proctitis (HR, 87.91; 95% CI, 48.12-160.61; <jats:italic>P </jats:italic>&amp;lt; .001). The incidence per 1000 person-years of any 1 of the 10 treatment-related complications was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.Conclusions and RelevanceThis cohort study found that, even after accounting for age-related symptoms and disease, PCA treatment was associated with higher rates of complications in the 12 years after treatment. Given the uncertain benefit of PCA treatment for most patients, these findings highlight the importance of patient counseling before PCA screening and treatment and provide a rationale for pursuing opportunities for cancer prevention.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"3 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImportanceEquecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.ObjectiveTo evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.Design, Setting, and ParticipantsThe FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022.InterventionsPatients received a single infusion of eque-cel at 1.0 × 106 CAR-positive T cells/kg after the lymphodepletion.Main Outcomes and MeasuresEfficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives.ResultsOf 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10−5. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell–associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell–associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days.Conclusions and RelevanceIn this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2000033946
{"title":"Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma","authors":"Chunrui Li, Keshu Zhou, Yongxian Hu, Dehui Zou, Lijuan Chen, Bing Chen, Jing Liu, Xi Zhang, Hanyun Ren, Kai Hu, Peng Liu, Jian-Qing Mi, Zhenyu Li, Kaiyang Ding, Di Wang, Wen Wang, Songbai Cai, Jianyong Li, Yongping Song, He Huang, Lugui Qiu","doi":"10.1001/jamaoncol.2024.4879","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4879","url":null,"abstract":"ImportanceEquecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.ObjectiveTo evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.Design, Setting, and ParticipantsThe FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022.InterventionsPatients received a single infusion of eque-cel at 1.0 × 10<jats:sup>6</jats:sup> CAR-positive T cells/kg after the lymphodepletion.Main Outcomes and MeasuresEfficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives.ResultsOf 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10<jats:sup>−5</jats:sup>. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell–associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell–associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days.Conclusions and RelevanceIn this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel.Trial RegistrationChinese Clinical Trial Registry Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.chictr.org.cn/showproj.html?proj=53503\">ChiCTR2000033946</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"196 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1001/jamaoncol.2024.5016
Stephanie Wang, Fumiko Chino, Edward Christopher Dee
This Viewpoint highlights financial toxicity specific to Asian American cancer survivors and presents steps forward within the framework of the social ecological model of health, considering individual, interpersonal, community, and policy-level dimensions.
{"title":"Financial Toxicity Among Asian American Cancer Survivors","authors":"Stephanie Wang, Fumiko Chino, Edward Christopher Dee","doi":"10.1001/jamaoncol.2024.5016","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5016","url":null,"abstract":"This Viewpoint highlights financial toxicity specific to Asian American cancer survivors and presents steps forward within the framework of the social ecological model of health, considering individual, interpersonal, community, and policy-level dimensions.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"18 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1001/jamaoncol.2024.4745
Stacie B Dusetzina,Frank S David
{"title":"Cancer Drug Access and Innovation Under the Inflation Reduction Act-A Balancing Act.","authors":"Stacie B Dusetzina,Frank S David","doi":"10.1001/jamaoncol.2024.4745","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4745","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"3 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1001/jamaoncol.2024.4748
Juan Esteban Velez-Hernandez,Julia T Geyer,Mateo Mejia Saldarriaga
{"title":"Hairy Kidneys and Sclerotic Bone Lesions.","authors":"Juan Esteban Velez-Hernandez,Julia T Geyer,Mateo Mejia Saldarriaga","doi":"10.1001/jamaoncol.2024.4748","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4748","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"97 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1001/jamaoncol.2024.4729
Maria E Cabanillas,Ramona Dadu,Renata Ferrarotto,Maria Gule-Monroe,Suyu Liu,Bryan Fellman,Michelle D Williams,Mark Zafereo,Jennifer R Wang,Charles Lu,Matthew Ning,Brian A McKinley,Scott E Woodman,Dzifa Duose,Gary B Gunn,Naifa L Busaidy,
ImportanceAnaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors.ObjectiveTo determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS).Design, Setting, and ParticipantsA phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023.InterventionsPatients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab.Main Outcomes and MeasuresThe primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months.ResultsForty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively.Conclusions and RelevanceIn this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS.Trial RegistrationClinicalTrials.gov Identifier: NCT03181100.
{"title":"Anti-Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial.","authors":"Maria E Cabanillas,Ramona Dadu,Renata Ferrarotto,Maria Gule-Monroe,Suyu Liu,Bryan Fellman,Michelle D Williams,Mark Zafereo,Jennifer R Wang,Charles Lu,Matthew Ning,Brian A McKinley,Scott E Woodman,Dzifa Duose,Gary B Gunn,Naifa L Busaidy,","doi":"10.1001/jamaoncol.2024.4729","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4729","url":null,"abstract":"ImportanceAnaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors.ObjectiveTo determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS).Design, Setting, and ParticipantsA phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023.InterventionsPatients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab.Main Outcomes and MeasuresThe primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months.ResultsForty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively.Conclusions and RelevanceIn this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS.Trial RegistrationClinicalTrials.gov Identifier: NCT03181100.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"97 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1001/jamaoncol.2024.4202
Alfred King-Yin Lam
{"title":"Impacts of Immunotherapy on Patients With Aggressive Thyroid Carcinomas.","authors":"Alfred King-Yin Lam","doi":"10.1001/jamaoncol.2024.4202","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4202","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"14 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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