Emma Sophia Zwanenburg, Charlotte El Klaver, Daniel D Wisselink, Cornelis J A Punt, P Snaebjornsson, Johannes Crezee, Arend G J Aalbers, Alexandra R M Brandt-Kerkhof, Andre J A Bremers, Pim J W A Burger, Hans F J Fabry, Floris T J Ferenschild, Sebastiaan Festen, Wilhemina M U van Grevenstein, Patrick H J Hemmer, Ignace H J T de Hingh, Niels F M Kok, M Kusters, G D Musters, Lotte Schoonderwoerd, J B Tuynman, Anthony W H van de Ven, Henderik L van Westreenen, M J Wiezer, David D E Zimmerman, Annette van Zweeden, Marcel G W Dijkgraaf, Pieter J Tanis
{"title":"Erratum: Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Locally Advanced Colon Cancer (COLOPEC): 5-Year Results of a Randomized Multicenter Trial.","authors":"Emma Sophia Zwanenburg, Charlotte El Klaver, Daniel D Wisselink, Cornelis J A Punt, P Snaebjornsson, Johannes Crezee, Arend G J Aalbers, Alexandra R M Brandt-Kerkhof, Andre J A Bremers, Pim J W A Burger, Hans F J Fabry, Floris T J Ferenschild, Sebastiaan Festen, Wilhemina M U van Grevenstein, Patrick H J Hemmer, Ignace H J T de Hingh, Niels F M Kok, M Kusters, G D Musters, Lotte Schoonderwoerd, J B Tuynman, Anthony W H van de Ven, Henderik L van Westreenen, M J Wiezer, David D E Zimmerman, Annette van Zweeden, Marcel G W Dijkgraaf, Pieter J Tanis","doi":"10.1200/JCO-26-00094","DOIUrl":"https://doi.org/10.1200/JCO-26-00094","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600094"},"PeriodicalIF":41.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085907","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}
Ruth A L Willems,Aniek E van Diepen,Esther N Dekker,Quisette P Janssen,Jacob L van Dam,Nynke Michiels,Casper W F van Eijck,Karlijn E P E Hermans,Bert A Bonsing,Koop P Bosscha,Stefan A W Bouwense,Olivier R Busch,Hugo Ten Cate,Peter-Paul L O Coene,Casper H J van Eijck,Nick van Es,Erwin van der Harst,Ignace H J T de Hingh,Tom M Karsten,Geert Kazemier,Marion B van der Kolk,Bas de Laat,Mike S L Liem,J Sven D Mieog,Vincent B Nieuwenhuijs,Gijsbert A Patijn,Mark Roest,Hjalmar C van Santvoort,Liselot Valkenburg-van Iersel,Roeland F de Wilde,Fennie Wit,Barbara M Zonderhuis,Marc G Besselink,Marjolein Y V Homs,Geertjan van Tienhoven,Johanna W Wilmink,Bas Groot Koerkamp,Judith de Vos-Geelen,
PURPOSEPancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of venous thromboembolism (VTE), which is burdensome and associated with decreased survival. Although neoadjuvant treatment is increasingly used in patients with PDAC, data on VTE in this setting remain scarce. This study evaluated VTE incidence during (neo)adjuvant therapy for resectable and borderline resectable PDAC and its relation to survival.METHODSThis study included patients from the investigator-initiated, multicenter, randomized controlled phase III PREOPANC-2 trial. Patients were randomly assigned to neoadjuvant 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin followed by surgery (FFX arm) or neoadjuvant gemcitabine-based chemoradiotherapy (CRT), followed by surgery and adjuvant gemcitabine (CRT arm). VTE was defined as both incidental and symptomatic lower- or upper-extremity deep vein thrombosis, pulmonary embolism (PE), splanchnic vein thrombosis, and catheter-related thrombosis. VTE occurrence was retrospectively evaluated from random assignment to 12 months after random assignment. The association with overall survival (OS) was analyzed using Cox regression analysis.RESULTSVTE was diagnosed in 28 of 325 patients (9%): nine (3%) preoperatively and 19 (8%) postoperatively. Most VTEs were symptomatic (54%). Although a higher proportion of patients developed postoperative VTE in the CRT arm (FFX 3% v CRT 12%, P = .02), the 12-month cumulative incidence did not differ between arms (6% v 11%, P = .06). Two patients died from PE-related causes in the CRT arm. VTE was independently associated with reduced OS (adjusted time-varying hazard ratio, 2.13, P = .002).CONCLUSIONVTE occurred in 9% of patients with (borderline) resectable PDAC undergoing (neo)adjuvant treatment in the year after random assignment and was associated with decreased OS. These results underscore the need for standardized reporting of thromboembolic events in clinical trials and future studies assessing the potential benefits of thromboprophylaxis during neoadjuvant therapy.
目的：胰腺导管腺癌（PDAC）与静脉血栓栓塞（VTE）的高风险相关，这是一个沉重的负担，并与生存率降低有关。尽管新辅助治疗越来越多地用于PDAC患者，但在这种情况下静脉血栓栓塞的数据仍然很少。本研究评估了可切除和边缘性可切除PDAC（新）辅助治疗期间的静脉血栓栓塞发生率及其与生存的关系。方法本研究纳入了来自研究者发起、多中心、随机对照III期preopac -2试验的患者。患者被随机分配到新辅助的5-氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂，然后进行手术（FFX组）或新辅助的基于吉西他滨的放化疗（CRT），然后进行手术和辅助的吉西他滨（CRT组）。VTE被定义为偶发和症状性下肢或上肢深静脉血栓形成、肺栓塞（PE）、内脏静脉血栓形成和导管相关血栓形成。从随机分配到随机分配后12个月回顾性评估静脉血栓栓塞的发生情况。采用Cox回归分析与总生存期（OS）的相关性。结果325例患者中28例（9%）确诊为静脉血栓栓塞，其中术前9例（3%），术后19例（8%）。大多数静脉血栓栓塞患者有症状（54%）。虽然CRT组术后发生静脉血栓栓塞的患者比例较高（FFX组为3%，CRT组为12%，P = 0.02），但两组间12个月的累积发生率没有差异（6% vs 11%, P = 0.06）。CRT组有两名患者死于pe相关原因。VTE与OS降低独立相关（调整时变风险比为2.13,P = 0.002）。结论：在随机分配后的一年内，接受（新）辅助治疗的（临界）可切除PDAC患者中有9%发生静脉血栓栓塞，并与OS降低相关。这些结果强调了在临床试验和未来的研究中对血栓栓塞事件进行标准化报告的必要性，以评估新辅助治疗期间血栓预防的潜在益处。
{"title":"Thromboembolic Events During Perioperative Therapy for Resectable and Borderline Resectable Pancreatic Cancer in the PREOPANC-2 Trial.","authors":"Ruth A L Willems,Aniek E van Diepen,Esther N Dekker,Quisette P Janssen,Jacob L van Dam,Nynke Michiels,Casper W F van Eijck,Karlijn E P E Hermans,Bert A Bonsing,Koop P Bosscha,Stefan A W Bouwense,Olivier R Busch,Hugo Ten Cate,Peter-Paul L O Coene,Casper H J van Eijck,Nick van Es,Erwin van der Harst,Ignace H J T de Hingh,Tom M Karsten,Geert Kazemier,Marion B van der Kolk,Bas de Laat,Mike S L Liem,J Sven D Mieog,Vincent B Nieuwenhuijs,Gijsbert A Patijn,Mark Roest,Hjalmar C van Santvoort,Liselot Valkenburg-van Iersel,Roeland F de Wilde,Fennie Wit,Barbara M Zonderhuis,Marc G Besselink,Marjolein Y V Homs,Geertjan van Tienhoven,Johanna W Wilmink,Bas Groot Koerkamp,Judith de Vos-Geelen, ","doi":"10.1200/jco-25-01935","DOIUrl":"https://doi.org/10.1200/jco-25-01935","url":null,"abstract":"PURPOSEPancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of venous thromboembolism (VTE), which is burdensome and associated with decreased survival. Although neoadjuvant treatment is increasingly used in patients with PDAC, data on VTE in this setting remain scarce. This study evaluated VTE incidence during (neo)adjuvant therapy for resectable and borderline resectable PDAC and its relation to survival.METHODSThis study included patients from the investigator-initiated, multicenter, randomized controlled phase III PREOPANC-2 trial. Patients were randomly assigned to neoadjuvant 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin followed by surgery (FFX arm) or neoadjuvant gemcitabine-based chemoradiotherapy (CRT), followed by surgery and adjuvant gemcitabine (CRT arm). VTE was defined as both incidental and symptomatic lower- or upper-extremity deep vein thrombosis, pulmonary embolism (PE), splanchnic vein thrombosis, and catheter-related thrombosis. VTE occurrence was retrospectively evaluated from random assignment to 12 months after random assignment. The association with overall survival (OS) was analyzed using Cox regression analysis.RESULTSVTE was diagnosed in 28 of 325 patients (9%): nine (3%) preoperatively and 19 (8%) postoperatively. Most VTEs were symptomatic (54%). Although a higher proportion of patients developed postoperative VTE in the CRT arm (FFX 3% v CRT 12%, P = .02), the 12-month cumulative incidence did not differ between arms (6% v 11%, P = .06). Two patients died from PE-related causes in the CRT arm. VTE was independently associated with reduced OS (adjusted time-varying hazard ratio, 2.13, P = .002).CONCLUSIONVTE occurred in 9% of patients with (borderline) resectable PDAC undergoing (neo)adjuvant treatment in the year after random assignment and was associated with decreased OS. These results underscore the need for standardized reporting of thromboembolic events in clinical trials and future studies assessing the potential benefits of thromboprophylaxis during neoadjuvant therapy.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"1 1","pages":"JCO2501935"},"PeriodicalIF":45.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072931","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}
PURPOSEImmune checkpoint inhibitors (ICIs) achieve sufficient receptor occupancy at much lower than standard approved doses. We hypothesized that ultra-low-dose nivolumab would retain clinical efficacy.PATIENTS AND METHODSIn this phase III randomized superiority trial, patients with advanced solid tumors (Eastern Cooperative Oncology Group 0-1) and progression on ≥1 prior line of systemic therapy were randomly assigned 1:1 to ultra-low-dose nivolumab (20 mg intravenously once every 2 weeks) or standard chemotherapy (docetaxel or paclitaxel, as per tumor type). Treatment continued until progression or intolerable toxicity. The primary end point was overall survival (OS).RESULTSFrom June 2020 to February 2024, we enrolled 500 patients: 250 per arm; 52% had head and neck and 36% lung cancers. The median number of prior lines of therapy was 1 (range, 1-8); 29% had received ≥2 prior lines. Median OS was significantly longer with ultra-low-dose nivolumab: 5.88 months (95% CI, 4.99 to 7.13) versus 4.70 months (95% CI, 3.91 to 5.65; hazard ratio [HR], 0.80 [95% CI, 0.66 to 0.97]; P = .022). One-year OS was 27.3% versus 16.9%. Median progression-free survival was similar: 2.04 months (95% CI, 2.00 to 2.10) with ultra-low-dose nivolumab and 2.09 months (95% CI, 2.04 to 2.17) with chemotherapy (HR, 1.03 [95% CI, 0.86 to 1.23]; P = .77). Grade ≥3 treatment-related adverse events were less frequent with ultra-low-dose nivolumab (42.5% v 60.8%; P < .001). Quality of life (QoL) was significantly better with ultra-low-dose nivolumab.CONCLUSIONUltra-low-dose nivolumab significantly improves OS versus chemotherapy in pretreated solid tumors, with fewer severe toxicities and better QoL. These findings support re-evaluation of ICI dosing strategies and may enhance global access.
{"title":"Efficacy and Safety of Ultra-Low-Dose Immunotherapy in Relapsed Refractory Solid Tumors: Phase III Superiority Randomized Trial (DELII).","authors":"Vanita Noronha,Vijay Patil,Nandini Menon,Minit Shah,Vikas Ostwal,Anant Ramaswamy,Prabhat Bhargava,Srushti Shah,Kavita Nawale,Ankush Shetake,Vijayalakshmi Mathrudev,Laxman Sahu,Shreya Mehta,Charushila Deshmukh,Savita Gaikwad,Shital Chavan,Ravi Narayan,Ravi Ingale,Sachin Dhumal,Rajiv Kumar Kaushal,Trupti Pai,Nilendu Purandare,Amit Janu,Nivedita Chakrabarty,Arpita Sahu,Purvi Haria,Arvind Vaidyanathan,Mehak Trikha,Sandeep Gedela,Shripad Banavali,Rajendra A Badwe,Kumar Prabhash","doi":"10.1200/jco-25-01546","DOIUrl":"https://doi.org/10.1200/jco-25-01546","url":null,"abstract":"PURPOSEImmune checkpoint inhibitors (ICIs) achieve sufficient receptor occupancy at much lower than standard approved doses. We hypothesized that ultra-low-dose nivolumab would retain clinical efficacy.PATIENTS AND METHODSIn this phase III randomized superiority trial, patients with advanced solid tumors (Eastern Cooperative Oncology Group 0-1) and progression on ≥1 prior line of systemic therapy were randomly assigned 1:1 to ultra-low-dose nivolumab (20 mg intravenously once every 2 weeks) or standard chemotherapy (docetaxel or paclitaxel, as per tumor type). Treatment continued until progression or intolerable toxicity. The primary end point was overall survival (OS).RESULTSFrom June 2020 to February 2024, we enrolled 500 patients: 250 per arm; 52% had head and neck and 36% lung cancers. The median number of prior lines of therapy was 1 (range, 1-8); 29% had received ≥2 prior lines. Median OS was significantly longer with ultra-low-dose nivolumab: 5.88 months (95% CI, 4.99 to 7.13) versus 4.70 months (95% CI, 3.91 to 5.65; hazard ratio [HR], 0.80 [95% CI, 0.66 to 0.97]; P = .022). One-year OS was 27.3% versus 16.9%. Median progression-free survival was similar: 2.04 months (95% CI, 2.00 to 2.10) with ultra-low-dose nivolumab and 2.09 months (95% CI, 2.04 to 2.17) with chemotherapy (HR, 1.03 [95% CI, 0.86 to 1.23]; P = .77). Grade ≥3 treatment-related adverse events were less frequent with ultra-low-dose nivolumab (42.5% v 60.8%; P < .001). Quality of life (QoL) was significantly better with ultra-low-dose nivolumab.CONCLUSIONUltra-low-dose nivolumab significantly improves OS versus chemotherapy in pretreated solid tumors, with fewer severe toxicities and better QoL. These findings support re-evaluation of ICI dosing strategies and may enhance global access.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"42 1","pages":"JCO2501546"},"PeriodicalIF":45.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069828","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}
Rahul Banerjee,Tracy King,Beth Faiman,Susie Harding,Aaron S Rosenberg,Vaishali Sanchorawala,Joseph R Mikhael,Andrew J Cowan
For over half a century, dexamethasone has been a backbone of treatment regimens for plasma cell disorders such as multiple myeloma (MM) and light-chain (AL) amyloidosis. Dexamethasone doses of approximately 40 milligrams (mg) once weekly are often continued for months or years despite accumulating evidence that they can cause dose-dependent toxicities such as cataracts and infections. Acute dexamethasone-related toxicities such as insomnia or pedal edema, even if low-grade by clinical criteria, can significantly interfere with patient quality of life. In the past 5 years, several trials have demonstrated the efficacy and improved tolerability of corticosteroid-sparing regimens in MM. In this review, we discuss these and other studies to comprehensively assess the role of dexamethasone in the modern era. In newly diagnosed MM, robust data support planned dexamethasone discontinuation after one to two cycles in older and frailer patients. In the maintenance setting, the risk-benefit ratio of prolonged dexamethasone is unfavorable. While randomized trials have shown that once-weekly dexamethasone adds value within doublet regimens in relapsed/refractory MM, its contribution to triplet and quadruplet regimens is uncertain. Furthermore, data suggest that indefinite dexamethasone may actually limit the feasibility and efficacy of subsequent postprogression therapies. In AL amyloidosis, dexamethasone 40 mg once weekly for 6 months is excessive and may predispose patients to volume overload. In our review, we also discuss dexamethasone as a premedication for CD38-targeted monoclonal antibodies (where it is no longer required after one to two cycles) and for supportive care (where lower doses of 4-8 mg as needed can often suffice). Despite the historical inertia of corticosteroid-containing regimens in clinical trials and practice guidelines, corticosteroid-sparing regimens warrant prospective investigation across the gamut of plasma cell disorders.
{"title":"Past, Present, and Future of Dexamethasone in Multiple Myeloma and AL Amyloidosis.","authors":"Rahul Banerjee,Tracy King,Beth Faiman,Susie Harding,Aaron S Rosenberg,Vaishali Sanchorawala,Joseph R Mikhael,Andrew J Cowan","doi":"10.1200/jco-25-01713","DOIUrl":"https://doi.org/10.1200/jco-25-01713","url":null,"abstract":"For over half a century, dexamethasone has been a backbone of treatment regimens for plasma cell disorders such as multiple myeloma (MM) and light-chain (AL) amyloidosis. Dexamethasone doses of approximately 40 milligrams (mg) once weekly are often continued for months or years despite accumulating evidence that they can cause dose-dependent toxicities such as cataracts and infections. Acute dexamethasone-related toxicities such as insomnia or pedal edema, even if low-grade by clinical criteria, can significantly interfere with patient quality of life. In the past 5 years, several trials have demonstrated the efficacy and improved tolerability of corticosteroid-sparing regimens in MM. In this review, we discuss these and other studies to comprehensively assess the role of dexamethasone in the modern era. In newly diagnosed MM, robust data support planned dexamethasone discontinuation after one to two cycles in older and frailer patients. In the maintenance setting, the risk-benefit ratio of prolonged dexamethasone is unfavorable. While randomized trials have shown that once-weekly dexamethasone adds value within doublet regimens in relapsed/refractory MM, its contribution to triplet and quadruplet regimens is uncertain. Furthermore, data suggest that indefinite dexamethasone may actually limit the feasibility and efficacy of subsequent postprogression therapies. In AL amyloidosis, dexamethasone 40 mg once weekly for 6 months is excessive and may predispose patients to volume overload. In our review, we also discuss dexamethasone as a premedication for CD38-targeted monoclonal antibodies (where it is no longer required after one to two cycles) and for supportive care (where lower doses of 4-8 mg as needed can often suffice). Despite the historical inertia of corticosteroid-containing regimens in clinical trials and practice guidelines, corticosteroid-sparing regimens warrant prospective investigation across the gamut of plasma cell disorders.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"1 1","pages":"JCO2501713"},"PeriodicalIF":45.3,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056383","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}
Pablo Hernáiz Driever,Uwe R Kordes,Ines B Brecht,Veronica Saletti,Michael J Fisher,Gail Doughton,Million Arefayene,Anna Rigazio,Nuria Lluch,Nereida Llorente,Scott J Diede,Hector Salvador
PURPOSENeurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN) can substantially affect quality of life. The capsule and granule formulations of selumetinib (ARRY-142886, AZD6244) are approved for pediatric patients with symptomatic, inoperable NF1-PN (age ≥1 to 3 years, region dependent). SPRINKLE (ClinicalTrials.gov identifier: NCT05309668) assessed pharmacokinetics (PK), safety, and palatability of the selumetinib granule formulation in children (age ≥1 to <7 years) with symptomatic, inoperable NF1-PN.METHODSParticipants enrolled into Global Cohort (GC)1 (≥4 to <7 years), GC2 (≥1 to <4 years), or the Japan Cohort (JC; ≥1 to <7 years) received selumetinib 25 mg/m2 (dose equivalent) twice a day in 28-day cycles. Primary objectives assessed single-dose selumetinib PK exposure (area under concentration-time curve from time 0-12 hours [AUC0-12]) in GCs and selumetinib safety. Secondary objectives assessed selumetinib and N-desmethyl selumetinib metabolite PK (single/multiple dose), and palatability. At first data cutoff (April 8, 2024), all participants had completed ≥3 cycles.RESULTSThere were 36 participants (GC1: n = 15, GC2: n = 17, JC: n = 4). Geometric mean (95% CI) selumetinib AUC0-12 (single dose) in GC1 (n = 13) and GC2 (n = 15) was 1,902 (1,647 to 2,197) and 1,699 (1,436 to 2,009) h × ng/mL, respectively. Primary PK end point was met: 95% CIs of AUC0-12 (single dose) were within the acceptance range on the basis of the capsule formulation exposure. Median duration of exposure was approximately 11 months (range, 2.7-25.3). 97.2% of participants had ≥1 treatment-related adverse event; most were grade 1 or 2 and none led to discontinuation or dose reduction. Most participants reported swallowing the medication without problems.CONCLUSIONSelumetinib granule formulation (25 mg/m2 dose equivalent, twice a day) had comparable exposure to selumetinib capsule formulation, and was palatable with a manageable safety profile. Selumetinib granule formulation is potentially suitable for young children with NF1-PN who cannot swallow capsules.
{"title":"Pharmacokinetics and Safety of Selumetinib Granule Formulation in Children With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas (SPRINKLE; phase I/II).","authors":"Pablo Hernáiz Driever,Uwe R Kordes,Ines B Brecht,Veronica Saletti,Michael J Fisher,Gail Doughton,Million Arefayene,Anna Rigazio,Nuria Lluch,Nereida Llorente,Scott J Diede,Hector Salvador","doi":"10.1200/jco-25-01447","DOIUrl":"https://doi.org/10.1200/jco-25-01447","url":null,"abstract":"PURPOSENeurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN) can substantially affect quality of life. The capsule and granule formulations of selumetinib (ARRY-142886, AZD6244) are approved for pediatric patients with symptomatic, inoperable NF1-PN (age ≥1 to 3 years, region dependent). SPRINKLE (ClinicalTrials.gov identifier: NCT05309668) assessed pharmacokinetics (PK), safety, and palatability of the selumetinib granule formulation in children (age ≥1 to <7 years) with symptomatic, inoperable NF1-PN.METHODSParticipants enrolled into Global Cohort (GC)1 (≥4 to <7 years), GC2 (≥1 to <4 years), or the Japan Cohort (JC; ≥1 to <7 years) received selumetinib 25 mg/m2 (dose equivalent) twice a day in 28-day cycles. Primary objectives assessed single-dose selumetinib PK exposure (area under concentration-time curve from time 0-12 hours [AUC0-12]) in GCs and selumetinib safety. Secondary objectives assessed selumetinib and N-desmethyl selumetinib metabolite PK (single/multiple dose), and palatability. At first data cutoff (April 8, 2024), all participants had completed ≥3 cycles.RESULTSThere were 36 participants (GC1: n = 15, GC2: n = 17, JC: n = 4). Geometric mean (95% CI) selumetinib AUC0-12 (single dose) in GC1 (n = 13) and GC2 (n = 15) was 1,902 (1,647 to 2,197) and 1,699 (1,436 to 2,009) h × ng/mL, respectively. Primary PK end point was met: 95% CIs of AUC0-12 (single dose) were within the acceptance range on the basis of the capsule formulation exposure. Median duration of exposure was approximately 11 months (range, 2.7-25.3). 97.2% of participants had ≥1 treatment-related adverse event; most were grade 1 or 2 and none led to discontinuation or dose reduction. Most participants reported swallowing the medication without problems.CONCLUSIONSelumetinib granule formulation (25 mg/m2 dose equivalent, twice a day) had comparable exposure to selumetinib capsule formulation, and was palatable with a manageable safety profile. Selumetinib granule formulation is potentially suitable for young children with NF1-PN who cannot swallow capsules.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"43 1","pages":"JCO2501447"},"PeriodicalIF":45.3,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056382","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":"Pediatric-Friendly Formulations: Critical to Maximizing Benefit of Novel Therapeutics Such as Selumetinib for Children With Neurofibromatosis and Other Neoplasms.","authors":"Brooke Bernhardt,Brenda J Weigel","doi":"10.1200/jco-25-02765","DOIUrl":"https://doi.org/10.1200/jco-25-02765","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"87 1","pages":"JCO2502765"},"PeriodicalIF":45.3,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056773","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}
Bradley J Stish, Gina L Mazza, Jones T Nauseef, Michael Sandon Humeniuk, Thomas J Smith, Cindy Tofthagen, Dayssy Alexandra Diaz Pardo, Christopher Chay, Andrew J Huang, Kushal Naha, Scott T Tagawa, Selina Chow, Kathryn J Ruddy, Maryam B Lustberg, Lucile L Adams-Campbell, Paul J Novotny, Charles L Loprinzi
Purpose: Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer.
Patients and methods: Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline at 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash-Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms.
Results: Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 (P = .02), and 6.89 (P < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 (P = .07), and 13.95 (P = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg (P = .042) and 5 mg (P < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo.
Conclusion: Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.
{"title":"Alliance A222001: Oxybutynin Versus Placebo for the Treatment of Hot Flashes in Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer.","authors":"Bradley J Stish, Gina L Mazza, Jones T Nauseef, Michael Sandon Humeniuk, Thomas J Smith, Cindy Tofthagen, Dayssy Alexandra Diaz Pardo, Christopher Chay, Andrew J Huang, Kushal Naha, Scott T Tagawa, Selina Chow, Kathryn J Ruddy, Maryam B Lustberg, Lucile L Adams-Campbell, Paul J Novotny, Charles L Loprinzi","doi":"10.1200/JCO-25-01486","DOIUrl":"10.1200/JCO-25-01486","url":null,"abstract":"<p><strong>Purpose: </strong>Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer.</p><p><strong>Patients and methods: </strong>Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline at 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash-Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms.</p><p><strong>Results: </strong>Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 (<i>P</i> = .02), and 6.89 (<i>P</i> < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 (<i>P</i> = .07), and 13.95 (<i>P</i> = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg (<i>P</i> = .042) and 5 mg (<i>P</i> < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo.</p><p><strong>Conclusion: </strong>Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501486"},"PeriodicalIF":41.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12871868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052342","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}
PURPOSEThe incidence of young-onset pancreatic cancer has increased rapidly; however, the dose-response relationship between alcohol consumption and the risk of incident young-onset pancreatic cancer remains unclear.METHODSA nationwide cohort of 6,263,770 individuals age 20 to 39 years who underwent national health screening in Korea between 2009 and 2012 was followed until December 2020. Heavy alcohol consumption was defined as ≥30 g/day for men and ≥16 g/day for women. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs.RESULTSA total of 1,515 cases of young-onset pancreatic cancer were identified. The cumulative incidence was consistently higher among heavy drinkers compared with nondrinkers or light-to-moderate drinkers (log-rank P < .001). Heavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer (aHR, 1.19 [95% CI, 1.004 to 1.42]), whereas light-to-moderate consumption was not (aHR, 1.04 [95% CI, 0.92 to 1.17]). In addition, alcohol consumption ≥3 times per week was associated with an increased risk (aHR, 1.23 [95% CI, 1.01 to 1.51]). No significant interactions were observed across most subgroups, including age, sex, obesity, smoking status, diabetes, and pancreatitis (all P for interaction > .05), except for physical activity (P = .011).CONCLUSIONHeavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer in a threshold dose-response manner. These findings suggest that early public health strategies to reduce heavy alcohol consumption among young adults may help mitigate the growing burden of young-onset pancreatic cancer.
{"title":"Threshold Dose-Response Association Between Alcohol Consumption and Risk of Young-Onset Pancreatic Cancer: A Nationwide Korean Cohort Study of Young Adults Age 20-39 Years.","authors":"Joo-Hyun Park,Jung Yong Hong,Kyungdo Han,Jay J Shen,Joon Oh Park,Young Suk Park,Ho Yeong Lim","doi":"10.1200/jco-25-01169","DOIUrl":"https://doi.org/10.1200/jco-25-01169","url":null,"abstract":"PURPOSEThe incidence of young-onset pancreatic cancer has increased rapidly; however, the dose-response relationship between alcohol consumption and the risk of incident young-onset pancreatic cancer remains unclear.METHODSA nationwide cohort of 6,263,770 individuals age 20 to 39 years who underwent national health screening in Korea between 2009 and 2012 was followed until December 2020. Heavy alcohol consumption was defined as ≥30 g/day for men and ≥16 g/day for women. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs.RESULTSA total of 1,515 cases of young-onset pancreatic cancer were identified. The cumulative incidence was consistently higher among heavy drinkers compared with nondrinkers or light-to-moderate drinkers (log-rank P < .001). Heavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer (aHR, 1.19 [95% CI, 1.004 to 1.42]), whereas light-to-moderate consumption was not (aHR, 1.04 [95% CI, 0.92 to 1.17]). In addition, alcohol consumption ≥3 times per week was associated with an increased risk (aHR, 1.23 [95% CI, 1.01 to 1.51]). No significant interactions were observed across most subgroups, including age, sex, obesity, smoking status, diabetes, and pancreatitis (all P for interaction > .05), except for physical activity (P = .011).CONCLUSIONHeavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer in a threshold dose-response manner. These findings suggest that early public health strategies to reduce heavy alcohol consumption among young adults may help mitigate the growing burden of young-onset pancreatic cancer.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"21 1","pages":"JCO2501169"},"PeriodicalIF":45.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033571","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}
PURPOSEThe neoCARHP aimed to investigate the efficacy and safety of investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) plus trastuzumab and pertuzumab, with carboplatin (TCbHP) or without carboplatin (THP), in stage II and III human epidermal growth factor receptor 2 (HER2)-positive breast cancer.METHODSThe neoCARHP was a multicenter, randomized, phase III, noninferiority study. Eligible patients were women age 18 years or older with previously untreated, stage II and III, HER2-positive invasive breast cancer. Patients were randomly assigned (1:1) to receive six 3-week cycles of TCbHP or THP. The primary end point was pathologic complete response (pCR) rate in the breast and axilla (ypT0/is ypN0) in the modified intention-to-treat (mITT) population (all randomly assigned patients receiving at least one dose of study treatment). Safety was evaluated in all patients who received any study treatment.RESULTSBetween April 30, 2021, and August 27, 2024, 774 patients were randomly assigned and 766 were included in the mITT population (382 in THP and 384 in TCbHP). pCR was achieved in 245 (64.1% [95% CI, 59.1 to 69.0]) patients in the THP group and 253 (65.9% [60.9-70.6]) in the TCbHP group (absolute difference, -1.8% [95% CI, -8.5 to 5.0]; odds ratio, 0.93 [95% CI, 0.69 to 1.25]; Pnoninferiority = .0089). The THP group had fewer grade 3 and 4 adverse events (20.7% v 34.6%) and serious adverse events (1.3% v 4.7%) than the TCbHP group. The most common grade 3 and 4 adverse events with THP were neutropenia (6.8% v 16.4% with TCbHP), leukopenia (5.5% v 14.8%), and diarrhea (2.6% v 4.2%). No treatment-associated deaths occurred.CONCLUSIONTHP provided noninferior pCR rates and improved tolerability compared with TCbHP. Omitting carboplatin may be applicable in HER2-positive breast cancer.
neoCARHP旨在研究研究者选择的紫杉醇（多西紫杉醇、紫杉醇或nab-紫杉醇）联合曲妥珠单抗和帕妥珠单抗，联合卡铂（TCbHP）或不联合卡铂（THP）治疗II期和III期人表皮生长因子受体2 （HER2）阳性乳腺癌的疗效和安全性。方法neoCARHP是一项多中心、随机、III期、非劣效性研究。符合条件的患者是年龄在18岁或以上的未接受治疗的II期和III期her2阳性浸润性乳腺癌女性。患者被随机分配（1:1）接受6个3周周期的TCbHP或THP治疗。主要终点是修改意向治疗（mITT）人群中乳腺和腋窝的病理完全缓解（pCR）率（ypT0/is ypN0）（所有随机分配的患者接受至少一个剂量的研究治疗）。对所有接受任何研究治疗的患者进行安全性评估。结果在2021年4月30日至2024年8月27日期间，774名患者被随机分配，766名患者被纳入mITT人群（382名THP患者和384名TCbHP患者）。在245例THP组（64.1% [95% CI, 59.1 ~ 69.0]）和253例TCbHP组（65.9%[60.9 ~ 70.6]）患者中进行了pCR检测（绝对差异为-1.8% [95% CI, -8.5 ~ 5.0]；优势比为0.93 [95% CI, 0.69 ~ 1.25]；非劣效性= 0.0089）。与TCbHP组相比，THP组3级和4级不良事件（20.7% vs 34.6%）和严重不良事件（1.3% vs 4.7%）较少。THP最常见的3级和4级不良事件是中性粒细胞减少（6.8% vs 16.4% TCbHP），白细胞减少（5.5% vs 14.8%）和腹泻（2.6% vs 4.2%）。无治疗相关死亡发生。结论与TCbHP相比，thp具有良好的pCR率和耐受性。省略卡铂可能适用于her2阳性乳腺癌。
{"title":"Neoadjuvant Taxane Plus Trastuzumab and Pertuzumab With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: The Randomized Noninferiority Phase III neoCARHP Trial.","authors":"Hong-Fei Gao,Guo-Lin Ye,Ying Lin,Qin Huang,Jie Dong,Yin Cao,Yan-Xia Zhao,Qian-Jun Chen,Shi-Hui Ma,Jie Ouyang,Jin-Hui Ye,Hua-Wei Yang,Yuan-Qi Zhang,Yong-Cheng Zhang,Gang-Ling Zhang,Wei Li,Yunjian Zhang,Zhi-Yong Wu,Ying-Yi Lin,Teng Zhu,Liu-Lu Zhang,Ci-Qiu Yang,Mei Yang,Hao Peng,Bo Chen,Yi-Tian Chen,Fei Ji,Min-Yi Cheng,Jie-Qing Li,Zefei Jiang,Kun Wang","doi":"10.1200/jco-25-02176","DOIUrl":"https://doi.org/10.1200/jco-25-02176","url":null,"abstract":"PURPOSEThe neoCARHP aimed to investigate the efficacy and safety of investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) plus trastuzumab and pertuzumab, with carboplatin (TCbHP) or without carboplatin (THP), in stage II and III human epidermal growth factor receptor 2 (HER2)-positive breast cancer.METHODSThe neoCARHP was a multicenter, randomized, phase III, noninferiority study. Eligible patients were women age 18 years or older with previously untreated, stage II and III, HER2-positive invasive breast cancer. Patients were randomly assigned (1:1) to receive six 3-week cycles of TCbHP or THP. The primary end point was pathologic complete response (pCR) rate in the breast and axilla (ypT0/is ypN0) in the modified intention-to-treat (mITT) population (all randomly assigned patients receiving at least one dose of study treatment). Safety was evaluated in all patients who received any study treatment.RESULTSBetween April 30, 2021, and August 27, 2024, 774 patients were randomly assigned and 766 were included in the mITT population (382 in THP and 384 in TCbHP). pCR was achieved in 245 (64.1% [95% CI, 59.1 to 69.0]) patients in the THP group and 253 (65.9% [60.9-70.6]) in the TCbHP group (absolute difference, -1.8% [95% CI, -8.5 to 5.0]; odds ratio, 0.93 [95% CI, 0.69 to 1.25]; Pnoninferiority = .0089). The THP group had fewer grade 3 and 4 adverse events (20.7% v 34.6%) and serious adverse events (1.3% v 4.7%) than the TCbHP group. The most common grade 3 and 4 adverse events with THP were neutropenia (6.8% v 16.4% with TCbHP), leukopenia (5.5% v 14.8%), and diarrhea (2.6% v 4.2%). No treatment-associated deaths occurred.CONCLUSIONTHP provided noninferior pCR rates and improved tolerability compared with TCbHP. Omitting carboplatin may be applicable in HER2-positive breast cancer.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"32 1","pages":"JCO2502176"},"PeriodicalIF":45.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033568","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}
Emily Alger,Olalekan Lee Aiyegbusi,Amylou C Dueck,Anna Minchom,Madeline Pe,John D Peipert,Claire Snyder,Stefan N Symeonides,Roger Wilson,Ethan Basch,Yu Qiao,Susan E Bates,Helen Bulbeck,Lizzie Dean,Massimo Di Maio,Aaron R Hansen,Olga Kholmanskikh,Ken Kobayashi,Dónal Landers,Christophe Le Tourneau,J Jack Lee,Brigette B Y Ma,Lynley V Marshall,Sheetal Patel,Joan Petrie,Gregory R Pond,Kieran Prior,Khadija R Rantell,John F Reeve,Olga Solovyeva,Nolan A Wages,Harald A Weber,Melanie J Calvert,Christina Yap
PURPOSEThere is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs.METHODSUsing the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion.RESULTSConsensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies.CONCLUSIONThis foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation-ultimately contributing to the development of safer, more effective therapies.
{"title":"International Consensus-Driven Recommendations for Patient-Reported Outcome Research Objectives in Early Phase Dose-Finding Oncology Trials: OPTIMISE-ROR.","authors":"Emily Alger,Olalekan Lee Aiyegbusi,Amylou C Dueck,Anna Minchom,Madeline Pe,John D Peipert,Claire Snyder,Stefan N Symeonides,Roger Wilson,Ethan Basch,Yu Qiao,Susan E Bates,Helen Bulbeck,Lizzie Dean,Massimo Di Maio,Aaron R Hansen,Olga Kholmanskikh,Ken Kobayashi,Dónal Landers,Christophe Le Tourneau,J Jack Lee,Brigette B Y Ma,Lynley V Marshall,Sheetal Patel,Joan Petrie,Gregory R Pond,Kieran Prior,Khadija R Rantell,John F Reeve,Olga Solovyeva,Nolan A Wages,Harald A Weber,Melanie J Calvert,Christina Yap","doi":"10.1200/jco-25-01625","DOIUrl":"https://doi.org/10.1200/jco-25-01625","url":null,"abstract":"PURPOSEThere is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs.METHODSUsing the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion.RESULTSConsensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies.CONCLUSIONThis foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation-ultimately contributing to the development of safer, more effective therapies.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"17 1","pages":"JCO2501625"},"PeriodicalIF":45.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033565","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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