Annals of Oncology最新文献

{"title":"SKYSCRAPER-07: falling short of the top","authors":"S.S. Kim, N.V. Uboha","doi":"10.1016/j.annonc.2026.09.010","DOIUrl":"10.1016/j.annonc.2026.09.010","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1457-1458"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036059","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":"Long-term benefit from immune checkpoint inhibition in squamous esophageal cancer","authors":"V.E. Blanco, E. Smyth","doi":"10.1016/j.annonc.2026.09.001","DOIUrl":"10.1016/j.annonc.2026.09.001","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1459-1460"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079480","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":"Retraction notice to “389P Monocyte reprogramming in high-grade serous ovarian cancer and chemotherapy impact: A single-cell RNA sequencing study”","authors":"K.I. Enikeeva, V.N. Pavlov","doi":"10.1016/j.annonc.2026.09.012","DOIUrl":"10.1016/j.annonc.2026.09.012","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Page 1572"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149308173","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":"Therapeutic targeting of RAS-mediated resistance in oncogene-driven lung cancer","authors":"F. Facchinetti,&nbsp;L. Friboulet,&nbsp;L. Liao,&nbsp;M. Peroni,&nbsp;S. Nakazawa,&nbsp;L. Zullo,&nbsp;M. Aldea,&nbsp;F. Pecci,&nbsp;M. Makarem,&nbsp;I. Alonso Garcia,&nbsp;R. Minari,&nbsp;B. Tuladhar,&nbsp;K. Ngo,&nbsp;A. Da Silva,&nbsp;L. Bigot,&nbsp;I. Odintsov,&nbsp;M.K.A. Koivu,&nbsp;A. Leonetti,&nbsp;J. Samaniego,&nbsp;E. Bernard,&nbsp;P.A. Jänne","doi":"10.1016/j.annonc.2026.08.004","DOIUrl":"10.1016/j.annonc.2026.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Despite the dramatic activity of next-generation targeted therapies, most patients with oncogene-driven lung cancers eventually relapse. Novel inhibitors are particularly active against on-target resistance, fostering the emergence of off-target resistance mechanisms. The current clinical development of RAS inhibitors hints at their potential role in overcoming off-target resistance mediated by <em>RAS</em> alterations.</div></div><div><h3>Patients and methods</h3><div>Using tissue and liquid biopsies, we assessed resistance mechanisms to first-line osimertinib in patients with epidermal growth factor receptor-mutant lung cancer and to <em>ALK</em>, <em>MET</em>, <em>ROS1</em>, and <em>RET</em> inhibitors, for a total of 590 patients. We established two patient-derived models with acquired <em>KRAS</em> mutations obtained at osimertinib progression, enabling <em>in vitro</em> and <em>in vivo</em> functional experiments.</div></div><div><h3>Results</h3><div>Among 312 patients progressing on first-line osimertinib, we observed a major complementary role of tissue and liquid biopsies in identifying resistance mechanisms. We identified <em>RAS</em> alterations in 35 of 312 patients (11.2%), with an enrichment in KRAS G12D (<em>n</em> = 10) and a paucity of KRAS G12C (<em>n</em> = 1) mutations. In patients with ALK-positive disease (<em>n</em> = 148), <em>RAS</em> alterations were more common at resistance to lorlatinib compared with second-generation inhibitors (14.7% versus 5%, <em>P</em> = 0.0444). Across <em>MET-</em>, <em>ROS1-</em>, and <em>RET-</em>driven lung cancers at progression to targeted agents, <em>RAS</em> alterations were detected in 7%-16% of the cases. In the two patient-derived models established at osimertinib resistance with acquired <em>KRAS</em> mutations (G12D and G12R, respectively), we tested the combinatorial effect of osimertinib with either the selective KRAS G12D inhibitor zoldonrasib or the pan-RAS inhibitor daraxonrasib. Both combinations demonstrated marked synergistic activity <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Conclusions</h3><div><em>RAS</em> alterations mediate resistance to targeted agents in ∼10% of oncogene-driven lung cancer. Rational combinations with novel RAS inhibitors are effective in preclinical models, providing the basis for their clinical investigation and extending the paradigm of precision oncology.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1549-1563"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787436","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":"Safety and antitumor activity of the first-in-class EGFR–HER3 bispecific antibody–drug conjugate iza-bren (BL-B01D1) in patients with pretreated locally advanced or metastatic breast cancer: a phase Ib study☆","authors":"J. Zhang,&nbsp;Y. Meng,&nbsp;Y. Du,&nbsp;T. Sun,&nbsp;J. Cui,&nbsp;Y. Chen,&nbsp;Y. Sun,&nbsp;Y. Wang,&nbsp;W. Chen,&nbsp;F. Xu,&nbsp;Y. Shi,&nbsp;Y. Chen,&nbsp;K. Wang,&nbsp;G. Jin,&nbsp;H. Zhou,&nbsp;Z. Zhuang,&nbsp;W. Xie,&nbsp;Z. Wang,&nbsp;M. Sun,&nbsp;Q. Wen,&nbsp;J. Wu","doi":"10.1016/j.annonc.2026.09.002","DOIUrl":"10.1016/j.annonc.2026.09.002","url":null,"abstract":"<div><h3>Background</h3><div>Bispecific antibody–drug conjugates (ADCs) may overcome limitations of monospecific ADCs. We report results from a phase Ib study of iza-bren, a first-in-class epidermal growth factor receptor–human epidermal growth factor receptor 3 bispecific ADC, in patients with heavily pretreated locally advanced or metastatic breast cancer (MBC).</div></div><div><h3>Patients and methods</h3><div>This multicenter study enrolled pretreated patients into three groups: human epidermal growth factor receptor 2 (HER2)-positive (<em>n</em> = 41), hormone receptor (HR)-positive/HER2-negative (<em>n</em> = 75), and triple-negative breast cancer (TNBC; <em>n</em> = 46). Patients received iza-bren 2.5 mg/kg i.v. on days 1 and 8 of each 21-day cycle. The primary endpoint was safety.</div></div><div><h3>Results</h3><div>All 162 enrolled patients were heavily pretreated (69.8% had ≥3 prior lines of therapy). Treatment-related adverse events occurred in 99.4% of patients, with grade ≥3 events observed in 77.8%, primarily hematological toxicities (neutropenia 55.6% and anemia 42.0%). Two treatment-related deaths occurred (febrile neutropenia and intracranial hemorrhage). No interstitial lung disease was reported. Confirmed objective response rates were 46.3% [95% confidence interval (CI) 30.7% to 62.6%] in HER2-positive, 37.3% (95% CI 26.4% to 49.3%) in HR-positive/HER2-negative, and 34.8% (95% CI 21.4% to 50.2%) in TNBC groups, with median progression-free survival of 5.8, 7.0, and 5.8 months, respectively.</div></div><div><h3>Conclusions</h3><div>Iza-bren exhibited a generally tolerable safety profile and demonstrated clinically meaningful antitumor activity across three major subtypes of heavily pretreated MBC.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1480-1488"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944141","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":"Atezolizumab with or without tiragolumab in unresectable esophageal squamous-cell carcinoma following definitive concurrent chemoradiotherapy (SKYSCRAPER-07): a randomised, phase III study","authors":"R.H. Xu,&nbsp;B.C. Cho,&nbsp;M. Chen,&nbsp;K. Muro,&nbsp;L. Wyrwicz,&nbsp;B. Li,&nbsp;S. Gao,&nbsp;C. Hsu,&nbsp;A. Turpin,&nbsp;F. Lordick,&nbsp;E. Cha,&nbsp;Q. Wu,&nbsp;S. Kim,&nbsp;J. Cai,&nbsp;L. Zhang,&nbsp;J. Fan,&nbsp;L. Wang,&nbsp;K. Sully,&nbsp;L. Wang,&nbsp;K. Goodman,&nbsp;I. Chau","doi":"10.1016/j.annonc.2026.07.413","DOIUrl":"10.1016/j.annonc.2026.07.413","url":null,"abstract":"<div><h3>Background</h3><div>New therapies are needed to improve survival in unresectable esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy (dCRT). We investigated the efficacy and safety of atezolizumab with or without tiragolumab versus placebo in this setting.</div></div><div><h3>Patients and methods</h3><div>SKYSCRAPER-07 (ClinicalTrials.gov: <span><span>NCT04543617</span><svg><path></path></svg></span>) is a global, randomised, placebo-controlled, phase III trial carried out at 166 centres in 28 countries. Adult patients with stage II-IVA locally advanced and selected stage IVB ESCC who had received dCRT were randomly assigned (1 : 1 : 1) to receive atezolizumab 1200 mg plus tiragolumab 600 mg, atezolizumab 1200 mg plus placebo, or placebo plus placebo (hereafter placebo) intravenously every 3 weeks for 17 cycles. Hierarchically tested primary endpoints are investigator-assessed progression-free survival (INV-PFS) then overall survival (OS) with atezolizumab plus tiragolumab versus placebo, followed by OS with atezolizumab plus placebo versus placebo.</div></div><div><h3>Results</h3><div>Between 28 September 2020 and 31 August 2023, 760 patients were assigned to receive atezolizumab plus tiragolumab (<em>n</em> = 257), atezolizumab plus placebo (<em>n</em> = 250), or placebo (<em>n</em> = 253). Overall, 564 (74.2%) patients were male and 477 (62.8%) were Asian. At a median survival follow-up of 25.0 months, atezolizumab plus tiragolumab versus placebo did not statistically improve INV-PFS [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65-1.03, <em>P</em> = 0.0947] or OS (HR 0.91, 95% CI 0.70-1.18, descriptive <em>P</em> = 0.4772). However, OS was significantly improved with atezolizumab plus placebo versus placebo (HR 0.69, 95% CI 0.52-0.91, descriptive <em>P</em> = 0.0085), as was INV-PFS (HR 0.74, 95% CI 0.58-0.93). Treatment-related adverse events occurred in 74.8%, 65.2%, and 55.4% of patients in the atezolizumab plus tiragolumab, atezolizumab plus placebo, and placebo groups, respectively, with treatment-related deaths occurring in 1.2%, 0.8%, and 1.6%, respectively.</div></div><div><h3>Conclusions</h3><div>The SKYSCRAPER-07 study did not meet the primary endpoint. Clinically meaningful improvements in OS and PFS were demonstrated with atezolizumab plus placebo versus placebo following dCRT for patients with unresectable ESCC.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1489-1501"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787464","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":"ESMO Clinical Practice Guideline Express Update on daraxonrasib in the treatment of metastatic pancreatic cancer","authors":"T. Conroy,&nbsp;M. Ducreux,&nbsp;ESMO Guidelines Committee","doi":"10.1016/j.annonc.2026.08.003","DOIUrl":"10.1016/j.annonc.2026.08.003","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1463-1466"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787491","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":"Sustained benefit of adjuvant olaparib in women with germline BRCA1- and BRCA2-associated high-risk HER2-negative early breast cancer: updated results from the OlympiA phase III trial","authors":"J.E. Garber,&nbsp;D. Cameron,&nbsp;C. Campbell,&nbsp;G. Yothers,&nbsp;M. Taboada,&nbsp;S. El-Abed,&nbsp;P. Rastogi,&nbsp;R. McConnell,&nbsp;A. Correa,&nbsp;S. Delaloge,&nbsp;W.T. Liu,&nbsp;P. Sharma,&nbsp;J. Bergh,&nbsp;W. Janni,&nbsp;J. Balmaña,&nbsp;N. Loman,&nbsp;T. Španić,&nbsp;S. Friedman,&nbsp;T. Freeman,&nbsp;A. Armstrong,&nbsp;A.N.J. Tutt","doi":"10.1016/j.annonc.2026.08.002","DOIUrl":"10.1016/j.annonc.2026.08.002","url":null,"abstract":"<div><h3>Background</h3><div>The randomised phase III OlympiA trial (NCT02032823) compared 1 year of adjuvant olaparib [oral poly (ADP-ribose) polymerase inhibitor] with placebo in 1836 patients with pathogenic/likely pathogenic <em>BRCA1</em> or <em>BRCA2</em> [germline <em>BRCA</em> pathogenic variants (g<em>BRCA</em>pvs)] germline variants and high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (BC). Previous interim analyses (IAs) demonstrated statistically significant improvements in invasive disease–free survival (IDFS), distant disease-free survival (DDFS) and overall survival (OS), irrespective of hormone receptor status, prior platinum administration, timing of prior chemotherapy or type of g<em>BRCA</em>pv. Herein are the results of the third prespecified IA with a median follow-up (MFU) of 6.1 years.</div></div><div><h3>Patients and methods</h3><div>Descriptive analyses are presented for the primary endpoint IDFS and key secondary endpoints of DDFS and OS. Estimates of the hazard ratio (HR) based on the stratified Cox’s proportional hazards model and 95% confidence intervals (CIs) are presented with yearly event rates at an MFU of ≤6.1 years. Safety analyses included adverse events of special interest (AESIs).</div></div><div><h3>Results</h3><div>Olaparib benefits were maintained in IDFS (HR 0.65, 95% CI 0.53-0.78), DDFS (HR 0.65, 95% CI 0.53-0.81) and OS (HR 0.72, 95% CI 0.56-0.93). The 6-year OS for olaparib versus placebo was 87.5% versus 83.2% (difference 4.4%, 95% CI 0.9% to 6.7%). Olaparib benefit was consistent across all key subgroups, including patients with high-risk hormone receptor-positive disease. There were fewer BRCA-associated new BC and ovarian/fallopian tube cancer cases and there was no increase in AESI risks (6.3% versus 9.3%), including myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) (0.4% versus 0.7%), with olaparib versus placebo.</div></div><div><h3>Conclusions</h3><div>At an MFU of 6.1 years, 1 year of adjuvant olaparib after (neo)adjuvant chemotherapy demonstrated ongoing clinically meaningful improvements in IDFS, DDFS and OS in patients with g<em>BRCA</em>pvs and high-risk, HER2-negative early BC, with acceptable toxicity and without increased risk of MDS/AML. These data continue to provide support for adjuvant olaparib in the treatment of g<em>BRCA</em>pv-associated high-risk, HER2-negative early BC.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1467-1479"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811805","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 pembrolizumab for the treatment of clear cell renal cell carcinoma: five-year results from the phase III KEYNOTE-564 study☆","authors":"N.B. Haas,&nbsp;T.B. Powles,&nbsp;P. Tomczak,&nbsp;S.H. Park,&nbsp;B. Venugopal,&nbsp;S.N. Symeonides,&nbsp;T. Ferguson,&nbsp;Y.-H. Chang,&nbsp;J.-L. Lee,&nbsp;P. Sawrycki,&nbsp;N. Sarwar,&nbsp;H. Gurney,&nbsp;M. Gross-Goupil,&nbsp;J.M. Burke,&nbsp;G. Doshi,&nbsp;J. Cornell,&nbsp;J.E. Burgents,&nbsp;R.F. Perini,&nbsp;T.K. Choueiri","doi":"10.1016/j.annonc.2026.08.006","DOIUrl":"10.1016/j.annonc.2026.08.006","url":null,"abstract":"<div><h3>Background</h3><div>The randomized phase III study KEYNOTE-564 (NCT03142334) established pembrolizumab after surgery as the standard of care for patients with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence. Prior analyses showed significantly improved disease-free survival (DFS) and overall survival (OS) with adjuvant pembrolizumab versus placebo. We present results from the fourth prespecified interim analysis, with a minimum follow-up of 5 years.</div></div><div><h3>Patients and methods</h3><div>Eligible adults with ccRCC at increased risk of recurrence were randomly assigned 1 : 1 to receive adjuvant pembrolizumab 200 mg or placebo every 3 weeks following nephrectomy or following nephrectomy and metastasectomy. Study treatment continued for ≤17 cycles (∼1 year), until recurrence, or until treatment discontinuation criteria were met. The primary endpoint was DFS per investigator assessment, and the key secondary endpoint was OS. Safety was a secondary endpoint.</div></div><div><h3>Results</h3><div>Overall, 994 participants were randomly assigned to pembrolizumab (<em>n</em> = 496) or placebo (<em>n</em> = 498). Median time from randomization to data cut-off (25 September 2024) was 70 months (range, 60-87). Pembrolizumab improved DFS versus placebo [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.59-0.86]; median DFS was not reached (NR) versus 68 months, and estimated 5-year DFS rates were 60.9% versus 52.2%, respectively. OS was improved with pembrolizumab over placebo (HR 0.66, 95% CI 0.48-0.90); median OS was NR for both arms with an estimated 5-year OS rate of 87.7% and 82.3%, respectively. DFS and OS benefits were consistent across key subgroups. Safety was largely unchanged since last analysis.</div></div><div><h3>Conclusions</h3><div>After a median follow-up of 70 months, adjuvant pembrolizumab demonstrated sustained DFS and OS benefit and a safety profile consistent with prior analyses. These findings continue to support the use of adjuvant pembrolizumab in ccRCC at increased risk of recurrence.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1564-1571"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148824293","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":"Nivolumab plus chemotherapy or ipilimumab versus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma: 5-year follow-up results from CheckMate 648","authors":"K. Kato,&nbsp;J. Ajani,&nbsp;Y. Doki,&nbsp;J. Xu,&nbsp;L. Wyrwicz,&nbsp;S. Motoyama,&nbsp;T. Ogata,&nbsp;H. Kawakami,&nbsp;C.-H. Hsu,&nbsp;A. Adenis,&nbsp;F. el Hajbi,&nbsp;M. Di Bartolomeo,&nbsp;M. Ignez Braghiroli,&nbsp;E. Holtved,&nbsp;T. Makino,&nbsp;M. Blum Murphy,&nbsp;J. Zhang,&nbsp;P. Sharma,&nbsp;B. He,&nbsp;M. Lei,&nbsp;I. Chau","doi":"10.1016/j.annonc.2026.08.001","DOIUrl":"10.1016/j.annonc.2026.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Both nivolumab plus chemotherapy (<em>P</em> &lt; 0.001) and nivolumab plus ipilimumab (<em>P</em> = 0.001) demonstrated significant overall survival (OS) benefit compared with chemotherapy for patients with previously untreated advanced esophageal squamous-cell carcinoma (ESCC) and programmed death-ligand 1 (PD-L1) ≥1%. We report OS and additional analyses at a minimum follow-up of 5 years.</div></div><div><h3>Patients and methods</h3><div>The open-label, phase III CheckMate 648 trial (NCT03143153) enrolled patients with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomly assigned 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. The primary endpoints were OS and progression-free survival (PFS) by blinded independent central review (BICR) in patients with tumor cell PD-L1 expression ≥1%. Key secondary endpoints included OS and PFS by BICR in all randomly assigned patients.</div></div><div><h3>Results</h3><div>In total, 970 patients were randomly assigned. At the 5-year minimum follow-up, OS improvement continued to be observed with nivolumab plus chemotherapy versus chemotherapy [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.48-0.79] and nivolumab plus ipilimumab versus chemotherapy (HR 0.62, 95% CI 0.48-0.80) in patients with tumor cell PD-L1 ≥1%. OS benefit was also observed in all randomly assigned patients (HR 0.77, 95% CI 0.65-0.92 for both nivolumab plus chemotherapy and nivolumab plus ipilimumab versus chemotherapy). PFS benefit was observed with nivolumab plus chemotherapy versus chemotherapy in the tumor cell PD-L1 ≥1% (HR 0.67, 95% CI 0.51-0.88) population but not with nivolumab plus ipilimumab versus chemotherapy (HR 1.03, 95% CI 0.78-1.35). Among all treated patients, grade 3-4 treatment-related adverse events were observed in 49% of patients in the nivolumab plus chemotherapy group, 33% in the nivolumab plus ipilimumab group, and 37% in the chemotherapy group.</div></div><div><h3>Conclusions</h3><div>Nivolumab-containing treatment regimens continued to demonstrate clinically meaningful OS benefit versus chemotherapy at the 5-year follow-up, with no new safety signals. These data further support nivolumab in combination with chemotherapy or ipilimumab as first-line treatment for patients with advanced ESCC.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 11","pages":"Pages 1502-1512"},"PeriodicalIF":80.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705089","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}