Journal of Clinical Oncology最新文献

{"title":"Next-Generation Molecular Residual Disease Assays: Do We Have the Tools to Evaluate Them Properly?","authors":"Dan Stetson, Paul Labrousse, Hugh Russell, David Shera, Chris Abbosh, Brian Dougherty, J Carl Barrett, Darren Hodgson, James Hadfield","doi":"10.1200/JCO.23.02301","DOIUrl":"10.1200/JCO.23.02301","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957472","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":"Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM).","authors":"Sehhoon Park, Richard Baldry, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Yu Jung Kim, Youngjoo Lee, Dong-Wan Kim, Sang-We Kim, Ki Hyeong Lee, Won Jae Lee, Jung Won Choi, Kyuha Chong, Jung-Il Lee, So-Hyeon Gwon, Nak-Hoon Son, Myung-Ju Ahn","doi":"10.1200/JCO.24.00708","DOIUrl":"10.1200/JCO.24.00708","url":null,"abstract":"<p><strong>Purpose: </strong>Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs.</p><p><strong>Materials and methods: </strong>In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6.</p><p><strong>Results: </strong>A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set-T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2.</p><p><strong>Conclusion: </strong>The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma.","authors":"Bruno Sangro, Peter R Galle, Robin Kate Kelley, Chaiyut Charoentum, Enrico N De Toni, Yurii Ostapenko, Jeong Heo, Ann-Lii Cheng, Andrea Wilson Woods, Charu Gupta, Jayne Abraham, Carrie L McCoy, Nikunj Patel, Alejandra Negro, Arndt Vogel, Ghassan K Abou-Alfa","doi":"10.1200/JCO.23.01462","DOIUrl":"10.1200/JCO.23.01462","url":null,"abstract":"<p><strong>Purpose: </strong>In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here.</p><p><strong>Methods: </strong>Participants were randomly assigned to receive STRIDE, durvalumab, or sorafenib. PROs were assessed (preplanned secondary outcome) using the European Organization for Research and Treatment of Cancer 30-item Quality of Life Questionnaire and the 18-item HCC module. Time to deterioration (TTD), change from baseline and improvement rate in global health status/quality of life (GHS/QoL), functioning, and disease-related symptoms were analyzed.</p><p><strong>Results: </strong>In total, 1,171 participants were randomly assigned to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389) and were evaluable for PRO assessments. Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms. TTD in GHS/QoL, physical functioning, fatigue, appetite loss, and abdominal pain was numerically longer for both STRIDE and durvalumab versus sorafenib. Clinically meaningful deterioration in PROs was not observed in any treatment arm. However, TTD in nausea and abdominal swelling was numerically longer for STRIDE versus sorafenib, and the likelihood of clinically meaningful improvement in GHS/QoL, role, emotional and social functioning, and disease-related symptoms was greater with STRIDE and durvalumab versus sorafenib. PROs with STRIDE and durvalumab were generally similar.</p><p><strong>Conclusion: </strong>Compared with sorafenib, STRIDE and durvalumab were associated with clinically meaningful, patient-centered GHS/QoL, functioning, and symptom benefits in people with uHCC. These findings support the benefits of the STRIDE regimen compared with sorafenib for a diverse population reflective of the global uHCC population.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I Trial of GD2.CART Cells Augmented With Constitutive Interleukin-7 Receptor for Treatment of High-Grade Pediatric CNS Tumors.","authors":"Frank Y Lin, Austin Stuckert, Candise Tat, Mark White, Lucia Ruggieri, Huimin Zhang, Birju Mehta, Natalia Lapteva, Zhuyong Mei, Angela Major, Sachin Thakkar, Thomas Shum, Kathan Parikh, Meng-Fen Wu, Holly B Lindsay, Lauren Scherer, Meghan Shekar, Patricia Baxter, Tao Wang, Bambi Grilley, Karen Moeller, John Hicks, Angshumoy Roy, Jamie Anastas, Fatema Malbari, Guillermo Aldave, Murali Chintagumpala, Susan Blaney, D Williams Parsons, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney, Bilal Omer","doi":"10.1200/JCO.23.02019","DOIUrl":"10.1200/JCO.23.02019","url":null,"abstract":"<p><strong>Purpose: </strong>T cells modified with chimeric antigen receptors (CARTs) have demonstrated efficacy for hematologic malignancies; however, benefit for patients with CNS tumors has been limited. To enhance T cell activity against GD2+ CNS malignancies, we modified GD2-directed CART cells (GD2.CARTs) with a constitutively active interleukin (IL)-7 receptor (C7R-GD2.CARTs).</p><p><strong>Methods: </strong>Patients age 1-21 years with H3K27-altered diffuse midline glioma (DMG) or other recurrent GD2-expressing CNS tumors were eligible for this phase I trial (ClinicalTrials.gov identifier: NCT04099797). All subjects received standard-of-care adjuvant radiation therapy or chemotherapy before study enrollment. The first treatment cohort received GD2.CARTs alone (1 × 10⁷ cells/m²), and subsequent cohorts received C7R-GD2.CARTs at two dose levels (1 × 10⁷ cells/m²; 3 × 10⁷ cells/m²). Standard lymphodepletion with cyclophosphamide and fludarabine was included at all dose levels.</p><p><strong>Results: </strong>Eleven patients (age 4-18 years) received therapy without dose-limiting toxicity. The GD2.CART cohort did not experience toxicity, but had disease progression after brief improvement of residual neurologic deficits (≤3 weeks). The C7R-GD2.CART cohort developed grade 1 tumor inflammation-associated neurotoxicity in seven of eight (88%) cases, controllable with anakinra. Cytokine release syndrome was observed in six of eight (75%, grade 1 in all but one patient) and associated with increased circulating IL-6 and IP-10 (<i>P</i> < .05). Patients receiving C7R-GD2.CARTs experienced temporary improvement from baseline neurologic deficits (range, 2 to >12 months), and seven of eight (88%) remained eligible for additional treatment cycles (range 2-4 cycles). Partial responses by iRANO criteria were observed in two of seven (29%) patients with DMG treated by C7R-GD2.CARTs.</p><p><strong>Conclusion: </strong>Intravenous GD2.CARTs with and without C7R were well tolerated. Patients treated with C7R-GD2.CARTs exhibited transient improvement of neurologic deficits and increased circulating cytokines/chemokines. Treatment with C7R-GD2.CARTs represents a novel approach warranting further investigation for children with these incurable CNS cancers.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selecting Patients With Oropharyngeal Cancer for Lower Dose Radiation.","authors":"Adam S Garden","doi":"10.1200/JCO.24.00395","DOIUrl":"10.1200/JCO.24.00395","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093549","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":"Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.","authors":"Yen-Shen Lu, Eznal Izwadi Bin Mohd Mahidin, Hamdy Azim, Yesim Eralp, Yoon Sim Yap, Seock-Ah Im, Julie Rihani, Erhan Gokmen, Ahmed El Bastawisy, Nuri Karadurmus, Yueh Ni Lim, Chun Sen Lim, Le Thanh Duc, Wei-Pang Chung, K Govind Babu, Konstantin Penkov, James Bowles, Teresa Delgar Alfaro, Jiwen Wu, Melissa Gao, Khemaies Slimane, Nagi S El Saghir","doi":"10.1200/JCO.24.00144","DOIUrl":"10.1200/JCO.24.00144","url":null,"abstract":"<p><strong>Purpose: </strong>A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).</p><p><strong>Methods: </strong>In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS).</p><p><strong>Results: </strong>Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; <i>P</i> = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm.</p><p><strong>Conclusion: </strong>First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptomeningeal Metastasis in the Era of CNS-Penetrant Tyrosine Kinase Inhibitor Therapy.","authors":"Mark Y Jeng, Helena A Yu","doi":"10.1200/JCO.24.01061","DOIUrl":"10.1200/JCO.24.01061","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468364","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":"Role of Minimally Invasive Techniques in the Management of Early-Stage Carcinoma of the Uterine Cervix.","authors":"Alexandra Bercow, Marcela G Del Carmen, J Alejandro Rauh-Hain, Alexander Melamed","doi":"10.1200/JCO.24.00656","DOIUrl":"10.1200/JCO.24.00656","url":null,"abstract":"<p><p><i>The Oncology Grand Rounds series is designed to place original reports published in the</i> Journal <i>into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in</i> Journal of Clinical Oncology<i>, to patients seen in their own clinical practice.</i></p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450577","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":"Erratum: Neoadjuvant Chemotherapy in High-Grade Myxoid Liposarcoma: Results of the Expanded Cohort of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish Sarcoma Groups (PSG).","authors":"","doi":"10.1200/JCO-24-01287","DOIUrl":"10.1200/JCO-24-01287","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500168","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":"Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.","authors":"Hatem A Azim, Samuel M Niman, Ann H Partridge, Isabelle Demeestere, Monica Ruggeri, Marco Colleoni, Cristina Saura, Chikako Shimizu, Anna B Saetersdal, Judith R Kroep, Audrey Mailliez, Ellen Warner, Virginia F Borges, Frédéric Amant, Andrea Gombos, Akemi Kataoka, Christine Rousset-Jablonski, Simona Borstnar, Junko Takei, Jeong Eon Lee, Janice M Walshe, Manuel Ruíz-Borrego, Halle C F Moore, Christobel Saunders, Vesna Bjelic-Radisic, Snezana Susnjar, Fatima Cardoso, Natalie J Klar, Tanja Spanic, Kathryn Ruddy, Martine Piccart, Larissa A Korde, Aron Goldhirsch, Richard D Gelber, Olivia Pagani, Fedro A Peccatori","doi":"10.1200/JCO.23.02292","DOIUrl":"10.1200/JCO.23.02292","url":null,"abstract":"<p><strong>Purpose: </strong>We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy.</p><p><strong>Patients and methods: </strong>POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy. The cumulative incidence of BC-free interval (BCFI) events was estimated according to the use of ovarian stimulation at diagnosis. The median follow-up was 41 months.</p><p><strong>Results: </strong>Two hundred seventy-three patients (53%) reported amenorrhea at enrollment, of whom 94% resumed menses within 12 months. Among 497 patients evaluable for pregnancy, 368 (74%) reported at least one pregnancy. Young age was the main factor associated with shorter time to pregnancy with cumulative incidences of pregnancy by 1 year of 63.5%, 54.3%, and 37.7% for patients age <35, 35-39, and 40-42 years, respectively. One hundred and seventy-nine patients (36%) had embryo/oocyte cryopreservation at diagnosis, of whom 68 reported embryo transfer after enrollment. Cryopreserved embryo transfer was the only ART associated with higher chance of pregnancy (odds ratio, 2.41 [95% CI, 1.75 to 4.95]). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis, 9.7% (95% CI, 6.0 to 15.4), compared with those who did not, 8.7% (95% CI, 6.0 to 12.5).</p><p><strong>Conclusion: </strong>In POSITIVE, fertility preservation using ovarian stimulation was not associated with short-term detrimental impact on cancer prognosis. Pregnancy rates were highest among those who underwent embryo/oocyte cryopreservation followed by embryo transfer.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173937","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}