Veronique Dieras,Giuseppe Curigliano,Miguel Martin,Florence Lerebours,Junji Tsurutani,Marie-France Savard,Katarzyna J Jerzak,Xichun Hu,Luciana Carla Martins de Aquino Pimentel,Ciara C O'Sullivan,Eriko Tokunaga,Alicia Okines,Chiun-Sheng Huang,William Jacot,Joohyuk Sohn,Eduardo Cronemberger Silva,Volkmar Mueller,Shan Yang,Giovanna Granata,Qi Shen,Libero Santarpia,Erika Hamilton
PURPOSEThe HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).PATIENTS AND METHODSPatients with centrally confirmed HER2+ MBC without evidence of progression post-induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo BID combined with trastuzumab/pertuzumab. Primary endpoint is investigator-assessed progression-free survival (PFS); secondary endpoints include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety.RESULTSBetween March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age: 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio = 0.641 [95% CI: 0.514, 0.799]; P < 0.0001; median PFS: 24.9 vs 16.3 months); a PFS benefit was seen regardless of presence/absence of BM or hormone receptor status. OS data remains immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (alanine aminotransferase: 28.2%; aspartate aminotransferase: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib due to TEAEs.CONCLUSIONSTucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.
{"title":"HER2CLIMB-05: A Phase 3 Study of Tucatinib Versus Placebo in Combination with Trastuzumab and Pertuzumab as First-line Maintenance Therapy for HER2+ Metastatic Breast Cancer.","authors":"Veronique Dieras,Giuseppe Curigliano,Miguel Martin,Florence Lerebours,Junji Tsurutani,Marie-France Savard,Katarzyna J Jerzak,Xichun Hu,Luciana Carla Martins de Aquino Pimentel,Ciara C O'Sullivan,Eriko Tokunaga,Alicia Okines,Chiun-Sheng Huang,William Jacot,Joohyuk Sohn,Eduardo Cronemberger Silva,Volkmar Mueller,Shan Yang,Giovanna Granata,Qi Shen,Libero Santarpia,Erika Hamilton","doi":"10.1200/jco-25-02600","DOIUrl":"https://doi.org/10.1200/jco-25-02600","url":null,"abstract":"PURPOSEThe HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).PATIENTS AND METHODSPatients with centrally confirmed HER2+ MBC without evidence of progression post-induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo BID combined with trastuzumab/pertuzumab. Primary endpoint is investigator-assessed progression-free survival (PFS); secondary endpoints include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety.RESULTSBetween March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age: 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio = 0.641 [95% CI: 0.514, 0.799]; P < 0.0001; median PFS: 24.9 vs 16.3 months); a PFS benefit was seen regardless of presence/absence of BM or hormone receptor status. OS data remains immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (alanine aminotransferase: 28.2%; aspartate aminotransferase: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib due to TEAEs.CONCLUSIONSTucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"6 1","pages":"101200JCO2502600"},"PeriodicalIF":45.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711116","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}
Enriqueta Felip,Heather A Wakelee,Chenqi Fu,Yu Deng,Fanny Masson,Barbara Gitlitz
{"title":"Reply to: \"Improving the Reporting of Long-Term Effects in the IMpower010 Trial\" and \"Adjuvant Atezolizumab in Early-Stage Non-Small Cell Lung Cancer: Signals, Silences, and the Need for Methodological Clarity\".","authors":"Enriqueta Felip,Heather A Wakelee,Chenqi Fu,Yu Deng,Fanny Masson,Barbara Gitlitz","doi":"10.1200/jco-25-02102","DOIUrl":"https://doi.org/10.1200/jco-25-02102","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"26 1","pages":"JCO2502102"},"PeriodicalIF":45.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717273","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}
Rakesh Popat,Meral Beksac,Meletios A Dimopoulos,Moshe E Gatt,Francesca Gay,Jae-Cheol Jo,Prashant Kapoor,Eirini Katodritou,K Martin Kortüm,Silvia Ling,Chandramouli Nagarajan,Kenshi Suzuki,Lugui Qiu,Maika Onishi,Grace Ku,Monique Dail,Nabanita Mukherjee,Jeremy A Ross,Mohamed Ali Badawi,Mary Jean Fusco,Edyta Dobkowska,Emma Arriola,Orlando F Bueno,Nizar J Bahlis,Shinsuke Iida,Philippe Moreau,Jason Valent,María-Victoria Mateos
PURPOSEVenetoclax, an oral BCL-2 inhibitor, has efficacy in t(11;14)-positive relapsed/refractory multiple myeloma (RRMM), which is enhanced by dexamethasone, which promotes BCL-2 dependency.METHODSThe randomized, open-label, phase III CANOVA study (ClinicalTrials.gov identifier: NCT03539744) enrolled adults with t(11;14)-positive RRMM who had received ≥2 previous lines of therapy. Patients were randomly assigned (1:1) to venetoclax-dexamethasone or pomalidomide-dexamethasone until progression or intolerable toxicity. The primary end point was independent review committee assessed-progression-free survival (PFS) in the intention-to-treat population analyzed by stratified log-rank test (two-sided type I error rate, α = .05), with hazard ratio (HR) and 95% CI estimated by stratified Cox proportional hazard model. Secondary end points included response rates, overall survival (OS), minimal residual disease (MRD) negativity rate (<10-5), and safety.RESULTSOverall, 263 patients were randomly assigned (venetoclax-dexamethasone, n = 133; pomalidomide-dexamethasone, n = 130). Median PFS was 9.9 months (95% CI, 6.9 to 12.6) with venetoclax-dexamethasone versus 5.8 months (95% CI, 3.8 to 9.2) with pomalidomide-dexamethasone (HR, 0.823 [95% CI, 0.596 to 1.136]; P = .24). Overall response and very good partial response or better rates were 62% and 39%, respectively, with venetoclax-dexamethasone versus 35% and 14% with pomalidomide-dexamethasone. MRD negativity rate was 8% with venetoclax-dexamethasone and 0% with pomalidomide-dexamethasone. Median OS was 32.4 months (95% CI, 26.4 to 40.7) with venetoclax-dexamethasone and 26.9 months (95% CI, 20.4 to 38.9) with pomalidomide-dexamethasone (HR, 0.856 [95% CI, 0.612 to 1.197]). Grade ≥3 treatment-emergent adverse event rates were 67% with venetoclax-dexamethasone versus 83% with pomalidomide-dexamethasone. There were 16 (12%) treatment-emergent deaths with venetoclax-dexamethasone versus 8 (6%) with pomalidomide-dexamethasone.CONCLUSIONThe primary end point of PFS was not met. PFS and OS were numerically longer with venetoclax-dexamethasone versus pomalidomide-dexamethasone in t(11;14)-positive RRMM. Consistent with previous studies, infections were associated with venetoclax-dexamethasone; no new safety signals were observed.
{"title":"Venetoclax-Dexamethasone Versus Pomalidomide-Dexamethasone in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma: Primary Results of the Randomized, Phase III CANOVA Study.","authors":"Rakesh Popat,Meral Beksac,Meletios A Dimopoulos,Moshe E Gatt,Francesca Gay,Jae-Cheol Jo,Prashant Kapoor,Eirini Katodritou,K Martin Kortüm,Silvia Ling,Chandramouli Nagarajan,Kenshi Suzuki,Lugui Qiu,Maika Onishi,Grace Ku,Monique Dail,Nabanita Mukherjee,Jeremy A Ross,Mohamed Ali Badawi,Mary Jean Fusco,Edyta Dobkowska,Emma Arriola,Orlando F Bueno,Nizar J Bahlis,Shinsuke Iida,Philippe Moreau,Jason Valent,María-Victoria Mateos","doi":"10.1200/jco-25-00924","DOIUrl":"https://doi.org/10.1200/jco-25-00924","url":null,"abstract":"PURPOSEVenetoclax, an oral BCL-2 inhibitor, has efficacy in t(11;14)-positive relapsed/refractory multiple myeloma (RRMM), which is enhanced by dexamethasone, which promotes BCL-2 dependency.METHODSThe randomized, open-label, phase III CANOVA study (ClinicalTrials.gov identifier: NCT03539744) enrolled adults with t(11;14)-positive RRMM who had received ≥2 previous lines of therapy. Patients were randomly assigned (1:1) to venetoclax-dexamethasone or pomalidomide-dexamethasone until progression or intolerable toxicity. The primary end point was independent review committee assessed-progression-free survival (PFS) in the intention-to-treat population analyzed by stratified log-rank test (two-sided type I error rate, α = .05), with hazard ratio (HR) and 95% CI estimated by stratified Cox proportional hazard model. Secondary end points included response rates, overall survival (OS), minimal residual disease (MRD) negativity rate (<10-5), and safety.RESULTSOverall, 263 patients were randomly assigned (venetoclax-dexamethasone, n = 133; pomalidomide-dexamethasone, n = 130). Median PFS was 9.9 months (95% CI, 6.9 to 12.6) with venetoclax-dexamethasone versus 5.8 months (95% CI, 3.8 to 9.2) with pomalidomide-dexamethasone (HR, 0.823 [95% CI, 0.596 to 1.136]; P = .24). Overall response and very good partial response or better rates were 62% and 39%, respectively, with venetoclax-dexamethasone versus 35% and 14% with pomalidomide-dexamethasone. MRD negativity rate was 8% with venetoclax-dexamethasone and 0% with pomalidomide-dexamethasone. Median OS was 32.4 months (95% CI, 26.4 to 40.7) with venetoclax-dexamethasone and 26.9 months (95% CI, 20.4 to 38.9) with pomalidomide-dexamethasone (HR, 0.856 [95% CI, 0.612 to 1.197]). Grade ≥3 treatment-emergent adverse event rates were 67% with venetoclax-dexamethasone versus 83% with pomalidomide-dexamethasone. There were 16 (12%) treatment-emergent deaths with venetoclax-dexamethasone versus 8 (6%) with pomalidomide-dexamethasone.CONCLUSIONThe primary end point of PFS was not met. PFS and OS were numerically longer with venetoclax-dexamethasone versus pomalidomide-dexamethasone in t(11;14)-positive RRMM. Consistent with previous studies, infections were associated with venetoclax-dexamethasone; no new safety signals were observed.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"5 1","pages":"JCO2500924"},"PeriodicalIF":45.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717275","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":"Improving the Reporting of Long-Term Effects in the IMpower010 Trial.","authors":"Paul de Boissieu,Sylvie Chevret","doi":"10.1200/jco-25-01352","DOIUrl":"https://doi.org/10.1200/jco-25-01352","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"61 1","pages":"JCO2501352"},"PeriodicalIF":45.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10Epub Date: 2025-11-06DOI: 10.1200/JCO-25-00559
Capucine Baldini, Loic Verlingue, Vincent Goldschmidt, Bernard Doger de Spéville, Julia Lostes, Antoine Italiano, Sophie Cousin, Gerald S Falchook, Andrea Necchi, Oscar Reig Torras, Elisa Fontana, Louise Carter, Jordi Rodon Ahnert, Jason R Brown, Leslie R DeMars, Kate Josephs, Amy Dickson, Cong Xu, Justin Bader, Carly Campbell, Rajiv Sharma, Meredith McKean
Purpose: Zelenectide pevedotin (BT8009) is a Bicycle Drug Conjugate comprising a highly selective Nectin-4-targeting Bicycle peptide, linked to monomethyl auristatin E. We report monotherapy dose-escalation results from Duravelo-1 (Phase I/II; ClinicalTrials.gov identifier: NCT04561362).
Methods: Adults with advanced/metastatic solid tumors associated with Nectin-4 expression received zelenectide pevedotin intravenously at 2.5, 5.0, or 7.5 mg/m2 once weekly on a 28-day cycle; or 7.5 mg/m2 on days 1 and 8 of a 21-day cycle; or 7.5 or 10.0 mg/m2 once every 2 weeks on a 28-day cycle. Primary objectives were to evaluate safety and tolerability; antitumor activity and pharmacokinetic characterization were secondary objectives.
Results: Forty-nine patients, most with urothelial carcinoma (UC; 25 of 49), received three previous lines of therapy (median). Common treatment-related adverse events (TRAEs) included nausea (49% [grade 3/4 2%]), likely because of a lack of prophylactic antiemetics during the dose-limiting toxicity period, and fatigue (39% [grade 3/4 6%]). The most common TRAEs of clinical interest were peripheral neuropathy (33% [grade 3/4 2%]), neutropenia (22% [grade 3/4 16%]), and skin reactions (22% [grade 3/4 2%]). The maximum tolerated dose was 7.5 mg/m2 once every 2 weeks; the recommended phase 2 doses were 5.0 mg/m2 once weekly and 7.5 mg/m2 on days 1 and 8 of a 21-day cycle. Across doses (efficacy-evaluable; all tumor types), the objective response rate (ORR) was 24% and the clinical benefit rate (CBR) was 48% (n = 10 of 42; 95% CI, 12.1 to 39.5); the ORR was 38% and the CBR was 57% for patients with UC (n = 8 of 21; 95% CI, 18.1 to 61.6). The median duration of response and the median follow-up for all patients were 11.1 and 7.4 months, respectively.
Conclusion: Zelenectide pevedotin monotherapy demonstrated a generally well-tolerated safety profile and preliminary efficacy, particularly in UC, supporting investigation of UC and non-UC populations in the expansion phase.
{"title":"First-in-Human, Phase I/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation.","authors":"Capucine Baldini, Loic Verlingue, Vincent Goldschmidt, Bernard Doger de Spéville, Julia Lostes, Antoine Italiano, Sophie Cousin, Gerald S Falchook, Andrea Necchi, Oscar Reig Torras, Elisa Fontana, Louise Carter, Jordi Rodon Ahnert, Jason R Brown, Leslie R DeMars, Kate Josephs, Amy Dickson, Cong Xu, Justin Bader, Carly Campbell, Rajiv Sharma, Meredith McKean","doi":"10.1200/JCO-25-00559","DOIUrl":"10.1200/JCO-25-00559","url":null,"abstract":"<p><strong>Purpose: </strong>Zelenectide pevedotin (BT8009) is a Bicycle Drug Conjugate comprising a highly selective Nectin-4-targeting Bicycle peptide, linked to monomethyl auristatin E. We report monotherapy dose-escalation results from Duravelo-1 (Phase I/II; ClinicalTrials.gov identifier: NCT04561362).</p><p><strong>Methods: </strong>Adults with advanced/metastatic solid tumors associated with Nectin-4 expression received zelenectide pevedotin intravenously at 2.5, 5.0, or 7.5 mg/m<sup>2</sup> once weekly on a 28-day cycle; or 7.5 mg/m<sup>2</sup> on days 1 and 8 of a 21-day cycle; or 7.5 or 10.0 mg/m<sup>2</sup> once every 2 weeks on a 28-day cycle. Primary objectives were to evaluate safety and tolerability; antitumor activity and pharmacokinetic characterization were secondary objectives.</p><p><strong>Results: </strong>Forty-nine patients, most with urothelial carcinoma (UC; 25 of 49), received three previous lines of therapy (median). Common treatment-related adverse events (TRAEs) included nausea (49% [grade 3/4 2%]), likely because of a lack of prophylactic antiemetics during the dose-limiting toxicity period, and fatigue (39% [grade 3/4 6%]). The most common TRAEs of clinical interest were peripheral neuropathy (33% [grade 3/4 2%]), neutropenia (22% [grade 3/4 16%]), and skin reactions (22% [grade 3/4 2%]). The maximum tolerated dose was 7.5 mg/m<sup>2</sup> once every 2 weeks; the recommended phase 2 doses were 5.0 mg/m<sup>2</sup> once weekly and 7.5 mg/m<sup>2</sup> on days 1 and 8 of a 21-day cycle. Across doses (efficacy-evaluable; all tumor types), the objective response rate (ORR) was 24% and the clinical benefit rate (CBR) was 48% (n = 10 of 42; 95% CI, 12.1 to 39.5); the ORR was 38% and the CBR was 57% for patients with UC (n = 8 of 21; 95% CI, 18.1 to 61.6). The median duration of response and the median follow-up for all patients were 11.1 and 7.4 months, respectively.</p><p><strong>Conclusion: </strong>Zelenectide pevedotin monotherapy demonstrated a generally well-tolerated safety profile and preliminary efficacy, particularly in UC, supporting investigation of UC and non-UC populations in the expansion phase.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3728-3738"},"PeriodicalIF":41.9,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12680284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458803","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":"Adjuvant Atezolizumab in Early-Stage Non-Small Cell Lung Cancer: Signals, Silences, and the Need for Methodological Clarity.","authors":"Jiebing He,Bo Zheng,Zhenrong Wang","doi":"10.1200/jco-25-01540","DOIUrl":"https://doi.org/10.1200/jco-25-01540","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"1 1","pages":"JCO2501540"},"PeriodicalIF":45.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10Epub Date: 2025-10-28DOI: 10.1200/JCO-25-02239
Eric Assenat, Meher Ben Abdelghani, Sophie Gourgou, Hervé Perrier, Faiza Khemissa Akouz, Romain Desgrippes, Marie-Pierre Galais, Chloé Janiszewski, Thibault Mazard, Yves Rinaldi, Côme Lepage, Raphael Tetreau, Pierre Senesse
{"title":"Erratum: Impact of Lean Body Mass-Based Oxaliplatin Dose Calculation on Neurotoxicity in Adjuvant Treatment of Stage III Colon Cancer: Results of the Phase II Randomized LEANOX Trial.","authors":"Eric Assenat, Meher Ben Abdelghani, Sophie Gourgou, Hervé Perrier, Faiza Khemissa Akouz, Romain Desgrippes, Marie-Pierre Galais, Chloé Janiszewski, Thibault Mazard, Yves Rinaldi, Côme Lepage, Raphael Tetreau, Pierre Senesse","doi":"10.1200/JCO-25-02239","DOIUrl":"10.1200/JCO-25-02239","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3774"},"PeriodicalIF":41.9,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145389720","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}
Priyanka A Pophali,Vaishalee P Kenkre,Christi Ann Hayes
{"title":"Bridging the Gap: Chimeric Antigen Receptor T-Cell Therapy in Diffuse Large B-Cell Lymphoma: Long-Term Benefit, Yet Real-World Complexity.","authors":"Priyanka A Pophali,Vaishalee P Kenkre,Christi Ann Hayes","doi":"10.1200/jco-25-02323","DOIUrl":"https://doi.org/10.1200/jco-25-02323","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"4 1","pages":"JCO2502323"},"PeriodicalIF":45.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717272","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":"BRUIN 313 and 314 Trials Open the Door for Noncovalent Bruton Tyrosine Kinase Inhibition as Initial Therapy for Chronic Lymphocytic Leukemia.","authors":"Matthew S Davids","doi":"10.1200/jco-25-02691","DOIUrl":"https://doi.org/10.1200/jco-25-02691","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"31 1","pages":"JCO2502691"},"PeriodicalIF":45.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704649","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}
PURPOSETo evaluate the efficacy and safety of adjuvant epirubicin plus cyclophosphamide followed by taxanes (EC-T) versus EC-T plus carboplatin (EC-TCb) in patients with early-stage triple-negative breast cancer (TNBC).PATIENTS AND METHODSIn this phase III trial, patients with TNBC with node-positive or node-negative (tumor size ≥1.0 cm) disease who received definitive surgery, were stratified by lymph node status and randomly assigned in a 1:1 ratio to receive four cycles of EC followed by four cycles T with or without carboplatin adjuvant chemotherapy. The primary end point was disease-free survival (DFS). Secondary end points included distant DFS (DDFS), overall survival (OS), and safety. This study had 80% power to detect a DFS hazard ratio (HR) of 0.64, with a two-sided type I error of 0.05.RESULTSA total of 786 patients were randomly assigned to receive EC-T (n = 391) or EC-TCb (n = 395) between March 2016 and March 2023. With a median follow-up of 4.52 (IQR, 2.83-6.06) years, 62 and 41 events were reported in the EC-T and EC-TCb arm, respectively. Adding carboplatin significantly improved DFS (HR, 0.66; [95% CI, 0.44 to 0.97]; P = .034), DDFS (HR, 0.61 [95% CI, 0.38 to 0.98]; P = .040), and OS (HR, 0.39 [95% CI, 0.16 to 0.94]; P = .029). Grade 3 to 4 adverse events were more frequent among the EC-TCb arm (49.9%) than the EC-T arm (38.7%), primarily driven by higher incidence of neutropenia (47.0% v 37.8%) and thrombocytopenia (4.5% v 0%). Other grade 3 to 4 toxicities were comparable.CONCLUSIONAdding carboplatin to adjuvant EC-T chemotherapy significantly improves DFS, DDFS, and OS in patients with early-stage TNBC. Although increased hematologic toxicity was observed, no new safety signals emerged.
目的评价表柔比星加环磷酰胺加紫杉烷（EC-T）与EC-T加卡铂（EC-TCb）治疗早期三阴性乳腺癌（TNBC）的疗效和安全性。患者和方法在这项III期试验中，接受最终手术的淋巴结阳性或淋巴结阴性（肿瘤大小≥1.0 cm） TNBC患者根据淋巴结状况分层，并按1:1的比例随机分配，接受4个周期的EC，然后4个周期的T伴或不伴卡铂辅助化疗。主要终点为无病生存期（DFS）。次要终点包括远端生存期（DDFS）、总生存期（OS）和安全性。本研究检测到DFS风险比（HR）为0.64的概率为80%，双侧I型误差为0.05。结果2016年3月至2023年3月，共786例患者随机分配接受EC-T （n = 391）或EC-TCb （n = 395）治疗。中位随访时间为4.52 （IQR, 2.83-6.06）年，EC-T组和EC-TCb组分别报告了62例和41例事件。添加卡铂可显著改善DFS （HR, 0.66; [95% CI, 0.44 ~ 0.97]; P = 0.034）、DDFS （HR, 0.61 [95% CI, 0.38 ~ 0.98]; P = 0.040）和OS （HR, 0.39 [95% CI, 0.16 ~ 0.94]; P = 0.029）。EC-TCb组3 - 4级不良事件发生率（49.9%）高于EC-T组（38.7%），主要原因是中性粒细胞减少（47.0% vs 37.8%）和血小板减少（4.5% vs 0%）发生率较高。其他3至4级毒性具有可比性。结论卡铂辅助EC-T化疗可显著改善早期TNBC患者的DFS、DDFS和OS。虽然观察到血液毒性增加，但没有出现新的安全信号。
{"title":"Adjuvant Epirubicin Plus Cyclophosphamide Followed by Taxanes With or Without Carboplatin in Early-Stage Triple-Negative Breast Cancer (RJBC 1501): A Randomized Phase III Trial.","authors":"Xiaosong Chen,Jiahui Huang,Haoting Shi,Juanying Zhu,Weizhu Wu,Guolin Ye,Qi He,Yong Shi,Anqin Zhang,Xiaohong Xie,Xiaodong Wang,Xiangjing Chen,Weili Wu,Jundong Wu,Zhian Li,Zhanwen Li,Yuechu Dai,Weili Ren,Qing Shao,Yongan Chen,Yong Zeng,Fengzhe Zhang,Shuwen Dong,Mark Daniel Pegram,Kunwei Shen","doi":"10.1200/jco-25-02412","DOIUrl":"https://doi.org/10.1200/jco-25-02412","url":null,"abstract":"PURPOSETo evaluate the efficacy and safety of adjuvant epirubicin plus cyclophosphamide followed by taxanes (EC-T) versus EC-T plus carboplatin (EC-TCb) in patients with early-stage triple-negative breast cancer (TNBC).PATIENTS AND METHODSIn this phase III trial, patients with TNBC with node-positive or node-negative (tumor size ≥1.0 cm) disease who received definitive surgery, were stratified by lymph node status and randomly assigned in a 1:1 ratio to receive four cycles of EC followed by four cycles T with or without carboplatin adjuvant chemotherapy. The primary end point was disease-free survival (DFS). Secondary end points included distant DFS (DDFS), overall survival (OS), and safety. This study had 80% power to detect a DFS hazard ratio (HR) of 0.64, with a two-sided type I error of 0.05.RESULTSA total of 786 patients were randomly assigned to receive EC-T (n = 391) or EC-TCb (n = 395) between March 2016 and March 2023. With a median follow-up of 4.52 (IQR, 2.83-6.06) years, 62 and 41 events were reported in the EC-T and EC-TCb arm, respectively. Adding carboplatin significantly improved DFS (HR, 0.66; [95% CI, 0.44 to 0.97]; P = .034), DDFS (HR, 0.61 [95% CI, 0.38 to 0.98]; P = .040), and OS (HR, 0.39 [95% CI, 0.16 to 0.94]; P = .029). Grade 3 to 4 adverse events were more frequent among the EC-TCb arm (49.9%) than the EC-T arm (38.7%), primarily driven by higher incidence of neutropenia (47.0% v 37.8%) and thrombocytopenia (4.5% v 0%). Other grade 3 to 4 toxicities were comparable.CONCLUSIONAdding carboplatin to adjuvant EC-T chemotherapy significantly improves DFS, DDFS, and OS in patients with early-stage TNBC. Although increased hematologic toxicity was observed, no new safety signals emerged.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"239 1","pages":"JCO2502412"},"PeriodicalIF":45.3,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710778","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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