JAMA OncologyPub Date : 2024-12-05DOI: 10.1001/jamaoncol.2024.5572
William E. Rosa, Andrew S. Epstein, Judith E. Nelson
{"title":"A Values Proposition for Cancer Care","authors":"William E. Rosa, Andrew S. Epstein, Judith E. Nelson","doi":"10.1001/jamaoncol.2024.5572","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5572","url":null,"abstract":"This Viewpoint discusses what a value proposition could look like in oncology and how it should reflect a clinician’s commitment to partner with patients to improve outcomes through individualized communication and shared decision-making centered on the patient’s values.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"76 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142777391","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}
JAMA OncologyPub Date : 2024-12-05DOI: 10.1001/jamaoncol.2024.5371
Hyo S. Han, Amy L. Aldrich, Saurabh K. Garg, R. Jared Weinfurtner, Jonathan V. Nguyen, Qianxing Mo, Junmin Whiting, Jennifer Childress, Hatem Soliman, Ricardo Costa, Avan Armaghani, Aixa Soyano, John Kiluk, Susan Hoover, Marie C. Lee, Nazanin Khakpour, Nithin Shenoi, Zena Jameel, Gary K. Koski, Brian J. Czerniecki
{"title":"Alteration of the Tumor Microenvironment With Intratumoral Dendritic Cells Before Chemotherapy in ERBB2 Breast Cancer","authors":"Hyo S. Han, Amy L. Aldrich, Saurabh K. Garg, R. Jared Weinfurtner, Jonathan V. Nguyen, Qianxing Mo, Junmin Whiting, Jennifer Childress, Hatem Soliman, Ricardo Costa, Avan Armaghani, Aixa Soyano, John Kiluk, Susan Hoover, Marie C. Lee, Nazanin Khakpour, Nithin Shenoi, Zena Jameel, Gary K. Koski, Brian J. Czerniecki","doi":"10.1001/jamaoncol.2024.5371","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5371","url":null,"abstract":"ImportanceCurrent chemotherapy regimens for patients with <jats:italic>ERBB2 </jats:italic>(formerly <jats:italic>HER</jats:italic>2)–positive breast cancer are associated with considerable morbidity. These patients may benefit from more effective and less toxic therapies.ObjectiveTo evaluate the safety, immunogenicity, and preliminary efficacy of intratumoral (IT) delivery of conventional type 1 dendritic cells (cDC1) in combination with <jats:italic>ERBB2</jats:italic>-targeted therapies.Design, Setting, and ParticipantsThis phase 1 (lead-in phase of a single-center phase 2 trial) nonrandomized clinical trial was conducted at Moffitt Cancer Center (Tampa, Florida). Patients were enrolled from October 2021 to October 2022. Data were analyzed in 2023 Patients with early-stage <jats:italic>ERBB2</jats:italic>-positive breast cancer with tumors 1 cm or larger were eligible.InterventionsTreatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m<jats:sup>2</jats:sup>, intravenously, 12 times weekly. Trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) were administered intravenously every 3 weeks for 6 cycles starting from day 1 of cDC1 injections. Two dose levels (DLs) of IT cDC1 (DL1 = 50 million and DL2 = 100 million cells) were evaluated, including 6 patients in each DL.Main Outcomes and MeasuresThe primary outcomes were the safety and immune response, and the secondary outcomes were the antitumor efficacy as measured by breast magnetic resonance imaging and residual cancer burden at surgery following neoadjuvant therapy.ResultsTwelve <jats:italic>ERBB2</jats:italic>-positive patients were enrolled and received treatment (DL1 = 6 and DL2 = 6). Nine patients had hormone receptor–positive disease and 3 had hormone receptor–negative disease, with clinical stage I (n = 5), II (n = 4), and III (n = 3). The most frequently observed adverse events with cDC1 were grade 1 to 2 chills (50%), fatigue (41.7%), headache (33%), and injection site reactions (33%). DL2 was associated with a diminished anti-<jats:italic>ERBB2</jats:italic> CD4 T-helper 1 blood response with a concomitant increase in innate and adaptive responses within the tumor. Preimmunotherapy and postimmunotherapy breast magnetic resonance imaging results showed 9 objective responses, 6 partial responses, 3 complete responses, and 3 stable diseases. Following surgery, 7 patients had a pathologic complete response.Conclusions and RelevanceIn this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT05325632\">NCT05325632</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"9 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782390","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}
JAMA OncologyPub Date : 2024-12-05DOI: 10.1001/jamaoncol.2024.5381
Katrina A. B. Goddard, Eric J. Feuer, Jeanne S. Mandelblatt, Rafael Meza, Theodore R. Holford, Jihyoun Jeon, Iris Lansdorp-Vogelaar, Roman Gulati, Natasha K. Stout, Nadia Howlader, Amy B. Knudsen, Daniel Miller, Jennifer L. Caswell-Jin, Clyde B. Schechter, Ruth Etzioni, Amy Trentham-Dietz, Allison W. Kurian, Sylvia K. Plevritis, John M. Hampton, Sarah Stein, Liyang P. Sun, Asad Umar, Philip E. Castle
{"title":"Estimation of Cancer Deaths Averted From Prevention, Screening, and Treatment Efforts, 1975-2020","authors":"Katrina A. B. Goddard, Eric J. Feuer, Jeanne S. Mandelblatt, Rafael Meza, Theodore R. Holford, Jihyoun Jeon, Iris Lansdorp-Vogelaar, Roman Gulati, Natasha K. Stout, Nadia Howlader, Amy B. Knudsen, Daniel Miller, Jennifer L. Caswell-Jin, Clyde B. Schechter, Ruth Etzioni, Amy Trentham-Dietz, Allison W. Kurian, Sylvia K. Plevritis, John M. Hampton, Sarah Stein, Liyang P. Sun, Asad Umar, Philip E. Castle","doi":"10.1001/jamaoncol.2024.5381","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5381","url":null,"abstract":"ImportanceCancer mortality has decreased over time, but the contributions of different interventions across the cancer control continuum to averting cancer deaths have not been systematically evaluated across major cancer sites.ObjectiveTo quantify the contributions of prevention, screening (to remove precursors [interception] or early detection), and treatment to cumulative number of cancer deaths averted from 1975 to 2020 for breast, cervical, colorectal, lung, and prostate cancers.Design, Setting, and ParticipantsIn this model-based study using population-level cancer mortality data, outputs from published models developed by the Cancer Intervention and Surveillance Modeling Network were extended to quantify cancer deaths averted through 2020. Model inputs were based on national data on risk factors, cancer incidence, cancer survival, and mortality due to other causes, and dissemination and effects of prevention, screening (for interception and early detection), and treatment. Simulated or modeled data using parameters derived from multiple birth cohorts of the US population were used.InterventionsPrimary prevention via smoking reduction (lung), screening for interception (cervix and colorectal) or early detection (breast, cervix, colorectal, and prostate), and therapy (breast, colorectal, lung, and prostate).Main Outcomes and MeasuresThe estimated cumulative number of cancer deaths averted with interventions vs no advances.ResultsAn estimated 5.94 million cancer deaths were averted for breast, cervical, colorectal, lung, and prostate cancers combined. Cancer prevention and screening efforts averted 8 of 10 of these deaths (4.75 million averted deaths). The contribution of each intervention varied by cancer site. Screening accounted for 25% of breast cancer deaths averted. Averted cervical cancer deaths were nearly completely averted through screening and removal of cancer precursors as treatment advances were modest during the study period. Averted colorectal cancer deaths were averted because of screening and removal of precancerous polyps or early detection in 79% and treatment advances in 21%. Most lung cancer deaths were avoided by smoking reduction (98%) because screening uptake was low and treatment largely palliative before 2014. Screening contributed to 56% of averted prostate cancer deaths.Conclusions and RelevanceOver the past 45 years, cancer prevention and screening accounted for most cancer deaths averted for these causes; however, their contribution varied by cancer site according to these models using population-level cancer mortality data. Despite progress, efforts to reduce the US cancer burden will require increased dissemination of effective interventions and new technologies and discoveries.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"16 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782391","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}
JAMA OncologyPub Date : 2024-11-14DOI: 10.1001/jamaoncol.2024.5145
Tonny Studsgaard Petersen, Kristian Karstoft, Freja Karuna Hemmingsen Sørup, Marie Lund, Allan Cramer
{"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}
{"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}
JAMA OncologyPub 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
{"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}
JAMA OncologyPub 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
{"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}
{"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}
JAMA OncologyPub Date : 2024-11-07DOI: 10.1001/jamaoncol.2024.5016
Stephanie Wang, Fumiko Chino, Edward Christopher Dee
{"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}
JAMA OncologyPub 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}