Pub Date : 2026-02-02DOI: 10.1016/j.annonc.2026.01.011
J S Deutsch, T R Cottrell, K Y Chen, C E De Andrea, E Baraban, P O Fiset, J J Jedrych, C E Orr, F X Real, R Salgado, C M Schürch, R A Scolyer, R Seethala, L M Sholl, S Signoretti, M Tetzlaff, H Wang, T Wang, A Weissferdt, X Xu, J Ziai, A Cimino-Mathews, J M Taube
Background: Pathologic response is an emerging surrogate marker for therapeutic efficacy and long-term patient outcomes. Updated guidelines for pan-tumor pathologic response assessment have recently been adopted for ongoing clinical trials and routine clinical care. The goal of this study was to prospectively evaluate the interobserver variability among pathologists in assessments of treatment response across tumor types, anatomic locations, and specimen types.
Materials and methods: A multi-institutional, international study led by the Society for Immunotherapy of Cancer was carried out to assess the concordance of pathologic response assessment using the pan-tumor criteria in neoadjuvant-treated resection specimens and on-treatment biopsies. Online lecture-based modules for scoring were developed, and 14 pathologists from multiple institutions were trained. The pathologists then assessed 42 specimens representing 12 different tumor types (total of n = 362 hematoxylin-eosin-stained slides) for the three tissue classes that are assessed: %residual viable tumor (RVT), %regression, and %necrosis. Pathologists were also surveyed regarding interest in and barriers related to pan-tumor pathologic response assessment, as well as quality and effectiveness of the training materials.
Results: Scoring of pathologic response using the pan-tumor system was highly reproducible, irrespective of disease location (primary tumor versus lymph node) or specimen type (resection versus biopsy), with intraclass correlation coefficients (ICCs) > 0.8 for %RVT, %regression, and %necrosis. Subset analyses also showed strong reproducibility of %RVT within almost all individual tumor types evaluated (ICC all ≥ 0.86). The poststudy survey completed by the participating pathologists was used to refine the training materials, and the revised modules are provided as a resource to the wider pathology and oncology communities.
Conclusions: This highly reproducible scoring system enables quantitative assessment of treatment response in pathology specimens across multiple tumor types, anatomic sites, disease stages, and therapies, akin to RECIST for radiographic assessment. We identified potential barriers to implementation and highlight strategies to overcome these challenges.
背景：病理反应是治疗效果和患者长期预后的替代指标。最近，正在进行的临床试验和常规临床护理采用了泛肿瘤病理反应评估的最新指南。本研究的目的是前瞻性地评估病理学家在评估不同肿瘤类型、解剖位置和标本类型的治疗反应时的观察者之间的差异。材料和方法：由癌症免疫治疗学会（Society for Immunotherapy of Cancer）领导的一项多机构国际研究，利用新佐剂治疗的切除标本和治疗中活检的泛肿瘤标准，评估病理反应评估的一致性。开发了基于讲座的在线评分模块，对来自多家机构的14名病理学家进行了培训。病理学家随后评估了代表12种不同肿瘤类型的42个标本（共n=362张h&e染色玻片），评估了三种组织类别：残余活肿瘤（RVT） %、消退%和坏死%。病理学家也被调查了对泛肿瘤病理反应评估的兴趣和障碍，以及培训材料的质量和有效性。结果：使用泛肿瘤系统进行病理反应评分具有高度可重复性，与疾病部位（原发肿瘤与淋巴结）或标本类型（切除与活检）无关，组内相关系数（ICCs）为>.8 %RVT， %消退和%坏死。亚群分析也显示，在几乎所有被评估的个体肿瘤类型中，%RVT的重复性很强（ICC均为0.86）。参与的病理学家完成的学习后调查被用来完善培训材料，修订后的模块作为资源提供给更广泛的病理学和肿瘤学社区。结论：这种高度可重复的评分系统可以对多种肿瘤类型、解剖部位、疾病分期和治疗的病理标本的治疗反应进行定量评估，类似于放射学评估的RECIST。我们确定了实施的潜在障碍，并强调了克服这些挑战的战略。
{"title":"Pan-tumor harmonization of pathologic response assessment for standardized data collection in neoadjuvant trials (PATHdata): results of a Society for Immunotherapy of Cancer multi-institutional reproducibility study.","authors":"J S Deutsch, T R Cottrell, K Y Chen, C E De Andrea, E Baraban, P O Fiset, J J Jedrych, C E Orr, F X Real, R Salgado, C M Schürch, R A Scolyer, R Seethala, L M Sholl, S Signoretti, M Tetzlaff, H Wang, T Wang, A Weissferdt, X Xu, J Ziai, A Cimino-Mathews, J M Taube","doi":"10.1016/j.annonc.2026.01.011","DOIUrl":"10.1016/j.annonc.2026.01.011","url":null,"abstract":"<p><strong>Background: </strong>Pathologic response is an emerging surrogate marker for therapeutic efficacy and long-term patient outcomes. Updated guidelines for pan-tumor pathologic response assessment have recently been adopted for ongoing clinical trials and routine clinical care. The goal of this study was to prospectively evaluate the interobserver variability among pathologists in assessments of treatment response across tumor types, anatomic locations, and specimen types.</p><p><strong>Materials and methods: </strong>A multi-institutional, international study led by the Society for Immunotherapy of Cancer was carried out to assess the concordance of pathologic response assessment using the pan-tumor criteria in neoadjuvant-treated resection specimens and on-treatment biopsies. Online lecture-based modules for scoring were developed, and 14 pathologists from multiple institutions were trained. The pathologists then assessed 42 specimens representing 12 different tumor types (total of n = 362 hematoxylin-eosin-stained slides) for the three tissue classes that are assessed: %residual viable tumor (RVT), %regression, and %necrosis. Pathologists were also surveyed regarding interest in and barriers related to pan-tumor pathologic response assessment, as well as quality and effectiveness of the training materials.</p><p><strong>Results: </strong>Scoring of pathologic response using the pan-tumor system was highly reproducible, irrespective of disease location (primary tumor versus lymph node) or specimen type (resection versus biopsy), with intraclass correlation coefficients (ICCs) > 0.8 for %RVT, %regression, and %necrosis. Subset analyses also showed strong reproducibility of %RVT within almost all individual tumor types evaluated (ICC all ≥ 0.86). The poststudy survey completed by the participating pathologists was used to refine the training materials, and the revised modules are provided as a resource to the wider pathology and oncology communities.</p><p><strong>Conclusions: </strong>This highly reproducible scoring system enables quantitative assessment of treatment response in pathology specimens across multiple tumor types, anatomic sites, disease stages, and therapies, akin to RECIST for radiographic assessment. We identified potential barriers to implementation and highlight strategies to overcome these challenges.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117694","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 : 2026-02-02DOI: 10.1016/j.annonc.2026.01.012
N Coleman, H N Tan, J Rodon Ahnert
Innovation in drug development is an evolving concept that can take many forms and is often confused with iteration, i.e. new versions of existing drug classes targeting familiar oncogenes. Yet meaningful innovation increasingly lies in translating approaches to historically 'untouchable' targets: transcription factors, tumor suppressors, and lineage-defining proteins, which have long resisted conventional pharmacologic approaches. At the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) 2025 Congress, a growing body of early-phase trials has continued to test and refine this paradigm, showcasing first-in-human studies and novel modalities aimed at drugging long-deemed inaccessible sites. In this manuscript, we review key highlights from ESMO TAT and other pivotal drug development meetings and delve into targeting these so-called 'untouchable' targets. Organized by target class (KRAS, MYC, TP53, WNT) and modality [proteolysis-targeting chimeras (PROTACs), antibody-drug conjugates, bispecifics], we explore how translational frameworks, rational trial design, and platform-specific engineering are reshaping what is now clinically feasible in drug development. Finally, we present early-phase data from the most compelling trials and compounds and explore what remains to be achieved to move beyond proof of concept into clinically meaningful benefits for patients with cancer.
{"title":"Progress in targeting the untouchables: emerging approaches for hard-to-drug cancer targets.","authors":"N Coleman, H N Tan, J Rodon Ahnert","doi":"10.1016/j.annonc.2026.01.012","DOIUrl":"10.1016/j.annonc.2026.01.012","url":null,"abstract":"<p><p>Innovation in drug development is an evolving concept that can take many forms and is often confused with iteration, i.e. new versions of existing drug classes targeting familiar oncogenes. Yet meaningful innovation increasingly lies in translating approaches to historically 'untouchable' targets: transcription factors, tumor suppressors, and lineage-defining proteins, which have long resisted conventional pharmacologic approaches. At the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) 2025 Congress, a growing body of early-phase trials has continued to test and refine this paradigm, showcasing first-in-human studies and novel modalities aimed at drugging long-deemed inaccessible sites. In this manuscript, we review key highlights from ESMO TAT and other pivotal drug development meetings and delve into targeting these so-called 'untouchable' targets. Organized by target class (KRAS, MYC, TP53, WNT) and modality [proteolysis-targeting chimeras (PROTACs), antibody-drug conjugates, bispecifics], we explore how translational frameworks, rational trial design, and platform-specific engineering are reshaping what is now clinically feasible in drug development. Finally, we present early-phase data from the most compelling trials and compounds and explore what remains to be achieved to move beyond proof of concept into clinically meaningful benefits for patients with cancer.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117718","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 : 2026-02-01Epub Date: 2025-10-18DOI: 10.1016/j.annonc.2025.10.010
C. Suarez , C. Rojas , S.J. Shin , P. Yanez Weber , L. Albiges , R. Motzer , H. Hammers , A. Peer , J.-L. Lee , W.H. Miller , T. Waddell , V. Neiman , D. Keizman , A. Zwenger Kloster , A. Weickhardt , R. Dziadziuszko , L. Suttner , M. Sharma , J.E. Burgents , T. Powles
Background
First-line triplet therapy may expand clinical benefit for advanced clear-cell renal cell carcinoma (ccRCC). The phase Ib/II KEYMAKER-U03 substudy 03A (NCT04626479) investigated novel pembrolizumab (pembro)-based regimens in this setting.
Patients and methods
Participants with advanced ccRCC and no prior systemic therapy were randomized 2 : 1 to quavonlimab (qmab)/pembro plus lenvatinib (lenva), favezelimab (fave)/pembro plus lenva, pembro plus lenva plus belzutifan (bel), and vibostolimab (vibo)/pembro plus bel or a concurrent reference treatment (pembro plus lenva). A safety lead-in of ∼10 participants occurred for all investigative treatments before randomization. Primary endpoints were objective response rate (ORR) per RECIST v1.1 by blinded independent central review in all randomized participants (excluding safety lead-in), and safety in all treated participants. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).
Results
As of 31 March 2025, 393 participants were enrolled. Median follow-up for randomized participants across the five cohorts ranged between 16 and 39 months. The ORR was 80.6% [95% confidence interval (CI) 68.6% to 89.6%] with pembro plus lenva, 71.3% (95% CI 60.0% to 80.8%) with qmab/pembro plus lenva, 62.7% (95% CI 48.1% to 75.9%) with fave/pembro plus lenva, 77.5% (95% CI 66.8% to 86.1%) with pembro plus lenva plus bel, and 42.5% (95% CI 31.5% to 54.1%) with vibo/pembro plus bel. Median PFS was 26.3 months (95% CI 15.3-39.8 months) with pembro plus lenva, 18.0 months (95% CI 11.6-34.3 months) with qmab/pembro plus lenva, 26.0 months (95% CI 8.2-31.8 months) with fave/pembro plus lenva, 31.8 months [95% CI 26.3 months-not reached (NR)] with pembro plus lenva plus bel, and 15.2 months (95% CI 12.4 months-NR) with vibo/pembro plus bel. Median OS was not reached in any arm. Grade ≥3 treatment-related adverse events occurred in 71.0% (44/62) of participants treated with pembro plus lenva, 73.3% (66/90) with qmab/pembro plus lenva, 86.9% (53/61) with fave/pembro plus lenva, 70.0% (63/90) with pembro plus lenva plus bel, and 68.9% (62/90) with vibo/pembro plus bel.
Conclusions
Observed efficacy and safety of pembro plus lenva were confirmatory of prior observations for this combination. ORR was similar to reference for pembro plus lenva plus bel and qmab/pembro plus lenva, but not the other investigative arms. Further investigation of pembro plus lenva plus bel and qmab/pembro plus lenva versus pembro plus lenva is ongoing in the phase III LITESPARK-012 study.
{"title":"Novel pembrolizumab-based treatments as first-line therapy in advanced clear-cell renal cell carcinoma: substudy 03A of the open-label, umbrella platform, phase I/II KEYMAKER-U03 trial☆","authors":"C. Suarez , C. Rojas , S.J. Shin , P. Yanez Weber , L. Albiges , R. Motzer , H. Hammers , A. Peer , J.-L. Lee , W.H. Miller , T. Waddell , V. Neiman , D. Keizman , A. Zwenger Kloster , A. Weickhardt , R. Dziadziuszko , L. Suttner , M. Sharma , J.E. Burgents , T. Powles","doi":"10.1016/j.annonc.2025.10.010","DOIUrl":"10.1016/j.annonc.2025.10.010","url":null,"abstract":"<div><h3>Background</h3><div>First-line triplet therapy may expand clinical benefit for advanced clear-cell renal cell carcinoma (ccRCC). The phase Ib/II KEYMAKER-U03 substudy 03A (NCT04626479) investigated novel pembrolizumab (pembro)-based regimens in this setting.</div></div><div><h3>Patients and methods</h3><div>Participants with advanced ccRCC and no prior systemic therapy were randomized 2 : 1 to quavonlimab (qmab)/pembro plus lenvatinib (lenva), favezelimab (fave)/pembro plus lenva, pembro plus lenva plus belzutifan (bel), and vibostolimab (vibo)/pembro plus bel or a concurrent reference treatment (pembro plus lenva). A safety lead-in of ∼10 participants occurred for all investigative treatments before randomization. Primary endpoints were objective response rate (ORR) per RECIST v1.1 by blinded independent central review in all randomized participants (excluding safety lead-in), and safety in all treated participants. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).</div></div><div><h3>Results</h3><div>As of 31 March 2025, 393 participants were enrolled. Median follow-up for randomized participants across the five cohorts ranged between 16 and 39 months. The ORR was 80.6% [95% confidence interval (CI) 68.6% to 89.6%] with pembro plus lenva, 71.3% (95% CI 60.0% to 80.8%) with qmab/pembro plus lenva, 62.7% (95% CI 48.1% to 75.9%) with fave/pembro plus lenva, 77.5% (95% CI 66.8% to 86.1%) with pembro plus lenva plus bel, and 42.5% (95% CI 31.5% to 54.1%) with vibo/pembro plus bel. Median PFS was 26.3 months (95% CI 15.3-39.8 months) with pembro plus lenva, 18.0 months (95% CI 11.6-34.3 months) with qmab/pembro plus lenva, 26.0 months (95% CI 8.2-31.8 months) with fave/pembro plus lenva, 31.8 months [95% CI 26.3 months-not reached (NR)] with pembro plus lenva plus bel, and 15.2 months (95% CI 12.4 months-NR) with vibo/pembro plus bel. Median OS was not reached in any arm. Grade ≥3 treatment-related adverse events occurred in 71.0% (44/62) of participants treated with pembro plus lenva, 73.3% (66/90) with qmab/pembro plus lenva, 86.9% (53/61) with fave/pembro plus lenva, 70.0% (63/90) with pembro plus lenva plus bel, and 68.9% (62/90) with vibo/pembro plus bel.</div></div><div><h3>Conclusions</h3><div>Observed efficacy and safety of pembro plus lenva were confirmatory of prior observations for this combination. ORR was similar to reference for pembro plus lenva plus bel and qmab/pembro plus lenva, but not the other investigative arms. Further investigation of pembro plus lenva plus bel and qmab/pembro plus lenva versus pembro plus lenva is ongoing in the phase III LITESPARK-012 study.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 2","pages":"Pages 229-240"},"PeriodicalIF":65.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336376","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 : 2026-02-01Epub Date: 2025-10-17DOI: 10.1016/j.annonc.2025.10.011
T. Powles , S.A. Hussain , M.A. Climent , I.G. Carbonero , J. Molina-Cerrillo , J. Puente , P. Borrega , J. Malik , L.-M. Dourthe , R. Jones , D. Castellano , I. Durán , Y. Loriot , G. Priyadarshini , B. Szabados , F. Jamal , Y.Q. Wang , N. Kotriwala , F. Jackson-Spence , C. Ackerman , E. Grande
Background
Six cycles of platinum-based chemotherapy followed by avelumab continues to be used in some circumstances in advanced/metastatic urothelial cancer (mUC). To investigate whether shorter chemotherapy duration improves quality of life (QoL) without worsening efficacy, this study compared three versus six cycles followed by avelumab.
Patients and methods
This randomized phase II trial compared three versus six cycles (3C arm versus 6C arm) of chemotherapy followed by avelumab in patients receiving first-line treatment for mUC. This trial had co-primary endpoints of patient-reported outcomes (PROs), defined as change from baseline to cycle 6 on the global health status/QoL score, and superior overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate, and safety. Here, we report the final PRO analysis and interim OS.
Results
A total of 267 patients were randomized (133 to 3C arm, 134 to 6C arm). Forty-two percent received gemcitabine/cisplatin and 58% gemcitabine/carboplatin. Seventy-eight percent and 40% of patients completed three and six cycles as allocated. Seventy-four percent of patients received avelumab in the 3C arm, versus 56% in the 6C arm. The mean QoL change between baseline and cycle 6 was 0 [95% confidence interval (CI) −5.9 to 5.2] in the 3C arm versus −8.5 (95% CI −14.1 to −2.9) in the 6C arm, with a significant difference favouring 3C (+8.5 points, 95% CI 0.7-16.3, P = 0.016). Improvement in PRO scores was observed in 41% (3C arm) versus 24% (6C arm) of patients. OS was not significant (18.9 months in both arms [hazard ratio (HR) 1.15, 95% CI 0.72-1.86, P = 0.56]. Median PFS was 8.0 months (95% CI 6.7-11.9 months) in the 3C arm versus 9.0 months (95% CI 6.9-12.7 months) in the 6C arm (HR 1.05, 95% CI 0.73-1.53). Median grade 3-4 treatment-related adverse events occurred in 11.9% (3C arm) versus 15.7% (6C arm).
Conclusions
Three cycles of chemotherapy followed by maintenance avelumab is associated with better QoL than six cycles. Randomized trials with patient-focused outcomes exploring shorter duration of therapy are feasible (NCT06892860).
{"title":"Three versus six cycles of platinum-based chemotherapy followed by avelumab maintenance as first-line treatment for advanced urothelial cancer: the phase II DISCUS trial☆","authors":"T. Powles , S.A. Hussain , M.A. Climent , I.G. Carbonero , J. Molina-Cerrillo , J. Puente , P. Borrega , J. Malik , L.-M. Dourthe , R. Jones , D. Castellano , I. Durán , Y. Loriot , G. Priyadarshini , B. Szabados , F. Jamal , Y.Q. Wang , N. Kotriwala , F. Jackson-Spence , C. Ackerman , E. Grande","doi":"10.1016/j.annonc.2025.10.011","DOIUrl":"10.1016/j.annonc.2025.10.011","url":null,"abstract":"<div><h3>Background</h3><div>Six cycles of platinum-based chemotherapy followed by avelumab continues to be used in some circumstances in advanced/metastatic urothelial cancer (mUC). To investigate whether shorter chemotherapy duration improves quality of life (QoL) without worsening efficacy, this study compared three versus six cycles followed by avelumab.</div></div><div><h3>Patients and methods</h3><div>This randomized phase II trial compared three versus six cycles (3C arm versus 6C arm) of chemotherapy followed by avelumab in patients receiving first-line treatment for mUC. This trial had co-primary endpoints of patient-reported outcomes (PROs), defined as change from baseline to cycle 6 on the global health status/QoL score, and superior overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate, and safety. Here, we report the final PRO analysis and interim OS.</div></div><div><h3>Results</h3><div>A total of 267 patients were randomized (133 to 3C arm, 134 to 6C arm). Forty-two percent received gemcitabine/cisplatin and 58% gemcitabine/carboplatin. Seventy-eight percent and 40% of patients completed three and six cycles as allocated. Seventy-four percent of patients received avelumab in the 3C arm, versus 56% in the 6C arm. The mean QoL change between baseline and cycle 6 was 0 [95% confidence interval (CI) −5.9 to 5.2] in the 3C arm versus −8.5 (95% CI −14.1 to −2.9) in the 6C arm, with a significant difference favouring 3C (+8.5 points, 95% CI 0.7-16.3, <em>P</em> = 0.016). Improvement in PRO scores was observed in 41% (3C arm) versus 24% (6C arm) of patients. OS was not significant (18.9 months in both arms [hazard ratio (HR) 1.15, 95% CI 0.72-1.86, <em>P</em> = 0.56]. Median PFS was 8.0 months (95% CI 6.7-11.9 months) in the 3C arm versus 9.0 months (95% CI 6.9-12.7 months) in the 6C arm (HR 1.05, 95% CI 0.73-1.53). Median grade 3-4 treatment-related adverse events occurred in 11.9% (3C arm) versus 15.7% (6C arm).</div></div><div><h3>Conclusions</h3><div>Three cycles of chemotherapy followed by maintenance avelumab is associated with better QoL than six cycles. Randomized trials with patient-focused outcomes exploring shorter duration of therapy are feasible (NCT06892860).</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 2","pages":"Pages 250-259"},"PeriodicalIF":65.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328074","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 : 2026-02-01Epub Date: 2025-10-18DOI: 10.1016/j.annonc.2025.10.009
A.W. Hahn , J. Chahoud , W.P. Skelton , Y. Yuan , A.J. Zurita-Saavedra , C. Kovitz , O. Alhalabi , M.T. Campbell , E. Jonasch , J.K. Lin , M. Desai , M.J.M.N. Santos , H. Hwang , P.G. Corn , P. Msaouel , N.M. Tannir
Background
First-line treatments for metastatic clear-cell renal-cell carcinoma (ccRCC) combine programmed cell death protein 1 (PD-1) immune checkpoint inhibition (ICI) with cytotoxic T-lymphocyte associated protein 4 ICI or angiogenesis targeted therapies (TT). Upon progression, common options include cabozantinib or lenvatinib + everolimus, although these regimens have never been directly compared. We hypothesized that lenvatinib + everolimus will improve progression-free survival (PFS) compared with cabozantinib after progression on PD-1 ICI.
Patients and methods
This multicenter, randomized phase II trial enrolled patients with metastatic ccRCC previously treated with one to two lines including PD-1 ICI. Participants received lenvatinib 18 mg/day + everolimus 5 mg/day versus cabozantinib 60 mg/day, stratified by International Metastatic RCC Database Consortium risk group and prior TT. A Bayesian optimal phase II design was used.
Results
In total 90 patients were randomized; 86 patients received at least one dose of assigned lenvatinib + everolimus (n = 40) or cabozantinib (n = 46). Median time from randomization to data cut-off date (1 August 2025) was 20 months (interquartile range 14.9-22.5 months). A total of 60 PFS events were observed. Median PFS was 15.7 months with lenvatinib + everolimus and 10.2 months with cabozantinib [hazard ratio 0.51, 95% confidence interval (CI) 0.29-0.89, P = 0.02]. The objective response rate was 52.6% with lenvatinib + everolimus and 38.6% with cabozantinib. Overall survival (OS) data were immature and inconclusive due to a low number of events (n = 24/86; 1-year OS probability 87.0% versus 84.6% [95% CI 0.47% to 2.38%] with lenvatinib + everolimus versus cabozantinib, respectively. Discontinuation rates due to toxicity were 20% with lenvatinib + everolimus and 10.9% with cabozantinib.
Conclusions
In this randomized phase II trial in metastatic ccRCC that progressed on prior PD-1 ICIs, lenvatinib + everolimus significantly prolonged PFS over cabozantinib. As the first head-to-head comparison of contemporary second-line or later treatments after ICI, these results are relevant to treatment sequencing and inform oncology practice.
{"title":"A multicenter randomized phase II trial of lenvatinib plus everolimus versus cabozantinib in patients with metastatic clear-cell RCC that progressed on PD-1 immune checkpoint inhibition (LenCabo)☆","authors":"A.W. Hahn , J. Chahoud , W.P. Skelton , Y. Yuan , A.J. Zurita-Saavedra , C. Kovitz , O. Alhalabi , M.T. Campbell , E. Jonasch , J.K. Lin , M. Desai , M.J.M.N. Santos , H. Hwang , P.G. Corn , P. Msaouel , N.M. Tannir","doi":"10.1016/j.annonc.2025.10.009","DOIUrl":"10.1016/j.annonc.2025.10.009","url":null,"abstract":"<div><h3>Background</h3><div>First-line treatments for metastatic clear-cell renal-cell carcinoma (ccRCC) combine programmed cell death protein 1 (PD-1) immune checkpoint inhibition (ICI) with cytotoxic T-lymphocyte associated protein 4 ICI or angiogenesis targeted therapies (TT). Upon progression, common options include cabozantinib or lenvatinib + everolimus, although these regimens have never been directly compared. We hypothesized that lenvatinib + everolimus will improve progression-free survival (PFS) compared with cabozantinib after progression on PD-1 ICI.</div></div><div><h3>Patients and methods</h3><div>This multicenter, randomized phase II trial enrolled patients with metastatic ccRCC previously treated with one to two lines including PD-1 ICI. Participants received lenvatinib 18 mg/day + everolimus 5 mg/day versus cabozantinib 60 mg/day, stratified by International Metastatic RCC Database Consortium risk group and prior TT. A Bayesian optimal phase II design was used.</div></div><div><h3>Results</h3><div>In total 90 patients were randomized; 86 patients received at least one dose of assigned lenvatinib + everolimus (<em>n</em> = 40) or cabozantinib (<em>n</em> = 46). Median time from randomization to data cut-off date (1 August 2025) was 20 months (interquartile range 14.9-22.5 months). A total of 60 PFS events were observed. Median PFS was 15.7 months with lenvatinib + everolimus and 10.2 months with cabozantinib [hazard ratio 0.51, 95% confidence interval (CI) 0.29-0.89, <em>P</em> = 0.02]. The objective response rate was 52.6% with lenvatinib + everolimus and 38.6% with cabozantinib. Overall survival (OS) data were immature and inconclusive due to a low number of events (<em>n</em> = 24/86; 1-year OS probability 87.0% versus 84.6% [95% CI 0.47% to 2.38%] with lenvatinib + everolimus versus cabozantinib, respectively. Discontinuation rates due to toxicity were 20% with lenvatinib + everolimus and 10.9% with cabozantinib.</div></div><div><h3>Conclusions</h3><div>In this randomized phase II trial in metastatic ccRCC that progressed on prior PD-1 ICIs, lenvatinib + everolimus significantly prolonged PFS over cabozantinib. As the first head-to-head comparison of contemporary second-line or later treatments after ICI, these results are relevant to treatment sequencing and inform oncology practice.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 2","pages":"Pages 241-249"},"PeriodicalIF":65.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336399","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 : 2026-02-01Epub Date: 2025-10-21DOI: 10.1016/j.annonc.2025.10.019
N. Harbeck , S. Modi , L. Pusztai , S. Ohno , J. Wu , S.-B. Kim , A. Yoshida , A. Fabi , X. Cao , R. Joseph , R. Li , B. Żurawski , S. Escrivá-de-Romaní , R. Meneguetti , A. Supavavej , S.-C. Chen , Z. Liu , C. Kelly , G. Curigliano , W.F. Symmans , J.-F. Boileau
Background
Neoadjuvant standard-of-care for HER2-positive early-stage breast cancer is trastuzumab + pertuzumab with polychemotherapy; however, existing regimens have high toxicity burdens and suboptimal outcomes. DESTINY-Breast11 assessed efficacy and safety of neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) versus dose-dense doxorubicin + cyclophosphamide (ddAC) followed by THP for high-risk (≥cT3cN0 or cT0–4cN1–3) HER2-positive disease.
Patients and methods
This open-label, phase III trial (147 sites, 18 countries) randomised adults 1 : 1 : 1 to T-DXd (×8 cycles), T-DXd-THP (4 + 4 cycles), or ddAC-THP (4 + 4 cycles). T-DXd-alone arm enrolment closed early following the Independent Data Monitoring Committee recommendation. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0; intent-to-treat population). Secondary endpoints included event-free survival (EFS; intent-to-treat population) and safety (safety analysis set).
Results
Between 25 October 2021 and 12 March 2025, 286 (T-DXd), 321 (T-DXd-THP), and 320 (ddAC-THP) female patients were randomised. pCR rates were 43.0% (T-DXd, n = 123), 67.3% (T-DXd-THP, n = 216), and 56.3% (ddAC-THP, n = 180). T-DXd-THP versus ddAC-THP absolute pCR rate difference was 11.2% [95% confidence interval (CI), 4.0% to 18.3%, P = 0.003], with benefit in hormone receptor (HR)-positive [61.4% (n/N = 145/236) versus 52.3% (n/N = 123/235); difference in pCR (ΔpCR) 9.1% (95% CI 0.2% to 17.9%)] and HR-negative [83.1% (n/N = 69/83) versus 67.1% (n/N = 57/85); ΔpCR 16.1% (95% CI 3.0% to 28.8%)] subgroups. Median EFS (T-DXd-THP versus ddAC-THP, maturity 4.5%) hazard ratio was 0.56 (95% CI 0.26 to 1.17). Grade ≥3 adverse events (AE; T-DXd, 22.6% (n = 64); T-DXd-THP, 37.5% (n = 120); ddAC-THP, 55.8% (n = 174)], serious AE [T-DXd, 10.2% (n = 29); T-DXd-THP, 10.6% (n = 34); ddAC-THP, 20.2% (n = 63)], and all-grade left-ventricular dysfunction [T-DXd, 0.7% (n = 2); T-DXd-THP, 1.3% (n = 4); ddAC-THP, 6.1% (n = 19)] rates were lower for T-DXd and T-DXd-THP than ddAC-THP. All-grade adjudicated drug-related interstitial lung disease/pneumonitis rates were low and similar across arms [T-DXd, 4.9% (n = 14); T-DXd-THP, 4.4% (n = 14); ddAC-THP, 5.1% (n = 16)]. Three treatment-related deaths occurred [T-DXd-THP, 0.3% (n = 1); ddAC-THP, 0.6% (n = 2)].
Conclusions
Neoadjuvant T-DXd-THP demonstrated statistically significant and clinically meaningful pCR benefit and improved safety versus ddAC-THP.
{"title":"Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): a randomised, open-label, multicentre, phase III trial☆","authors":"N. Harbeck , S. Modi , L. Pusztai , S. Ohno , J. Wu , S.-B. Kim , A. Yoshida , A. Fabi , X. Cao , R. Joseph , R. Li , B. Żurawski , S. Escrivá-de-Romaní , R. Meneguetti , A. Supavavej , S.-C. Chen , Z. Liu , C. Kelly , G. Curigliano , W.F. Symmans , J.-F. Boileau","doi":"10.1016/j.annonc.2025.10.019","DOIUrl":"10.1016/j.annonc.2025.10.019","url":null,"abstract":"<div><h3>Background</h3><div>Neoadjuvant standard-of-care for HER2-positive early-stage breast cancer is trastuzumab + pertuzumab with polychemotherapy; however, existing regimens have high toxicity burdens and suboptimal outcomes. DESTINY-Breast11 assessed efficacy and safety of neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) versus dose-dense doxorubicin + cyclophosphamide (ddAC) followed by THP for high-risk (≥cT3cN0 or cT0–4cN1–3) HER2-positive disease.</div></div><div><h3>Patients and methods</h3><div>This open-label, phase III trial (147 sites, 18 countries) randomised adults 1 : 1 : 1 to T-DXd (×8 cycles), T-DXd-THP (4 + 4 cycles), or ddAC-THP (4 + 4 cycles). T-DXd-alone arm enrolment closed early following the Independent Data Monitoring Committee recommendation. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0; intent-to-treat population). Secondary endpoints included event-free survival (EFS; intent-to-treat population) and safety (safety analysis set).</div></div><div><h3>Results</h3><div>Between 25 October 2021 and 12 March 2025, 286 (T-DXd), 321 (T-DXd-THP), and 320 (ddAC-THP) female patients were randomised. pCR rates were 43.0% (T-DXd, <em>n</em> = 123), 67.3% (T-DXd-THP, <em>n</em> = 216), and 56.3% (ddAC-THP, <em>n</em> = 180). T-DXd-THP versus ddAC-THP absolute pCR rate difference was 11.2% [95% confidence interval (CI), 4.0% to 18.3%, <em>P</em> = 0.003], with benefit in hormone receptor (HR)-positive [61.4% (<em>n</em>/<em>N</em> = 145/236) versus 52.3% (<em>n</em>/<em>N</em> = 123/235); difference in pCR (ΔpCR) 9.1% (95% CI 0.2% to 17.9%)] and HR-negative [83.1% (<em>n</em>/<em>N</em> = 69/83) versus 67.1% (<em>n</em>/<em>N</em> = 57/85); ΔpCR 16.1% (95% CI 3.0% to 28.8%)] subgroups. Median EFS (T-DXd-THP versus ddAC-THP, maturity 4.5%) hazard ratio was 0.56 (95% CI 0.26 to 1.17). Grade ≥3 adverse events (AE; T-DXd, 22.6% (<em>n</em> = 64); T-DXd-THP, 37.5% (<em>n</em> = 120); ddAC-THP, 55.8% (<em>n</em> = 174)], serious AE [T-DXd, 10.2% (<em>n</em> = 29); T-DXd-THP, 10.6% (<em>n</em> = 34); ddAC-THP, 20.2% (<em>n</em> = 63)], and all-grade left-ventricular dysfunction [T-DXd, 0.7% (<em>n</em> = 2); T-DXd-THP, 1.3% (<em>n</em> = 4); ddAC-THP, 6.1% (<em>n</em> = 19)] rates were lower for T-DXd and T-DXd-THP than ddAC-THP. All-grade adjudicated drug-related interstitial lung disease/pneumonitis rates were low and similar across arms [T-DXd, 4.9% (<em>n</em> = 14); T-DXd-THP, 4.4% (<em>n</em> = 14); ddAC-THP, 5.1% (<em>n</em> = 16)]. Three treatment-related deaths occurred [T-DXd-THP, 0.3% (<em>n</em> = 1); ddAC-THP, 0.6% (<em>n</em> = 2)].</div></div><div><h3>Conclusions</h3><div>Neoadjuvant T-DXd-THP demonstrated statistically significant and clinically meaningful pCR benefit and improved safety versus ddAC-THP.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 2","pages":"Pages 166-179"},"PeriodicalIF":65.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353374","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 : 2026-02-01Epub Date: 2025-10-17DOI: 10.1016/j.annonc.2025.10.005
S. Johnston , M. Martin , J. O’Shaughnessy , R. Hegg , S.M. Tolaney , V. Guarneri , L. Del Mastro , M. Campone , J. Sohn , F. Boyle , J. Cortes , H.S. Rugo , M.P. Goetz , E.P. Hamilton , C.-S. Huang , E. Senkus , I. Cicin , L. Testa , P. Neven , J. Huober , N. Harbeck
Background
Adjuvant abemaciclib combined with endocrine therapy (ET) significantly improved invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, node-positive, high-risk early breast cancer (EBC). The impact on overall survival (OS) remained unknown.
Patients and methods
In the phase III monarchE trial (NCT03155997), patients received ET for at least 5 years with or without abemaciclib for 2 years. In this article, we report the primary OS results, a key secondary endpoint, and updated estimates of IDFS and distant relapse-free survival (DRFS).
Results
Overall, 5637 patients underwent randomization, with 2808 assigned to abemaciclib–ET, and 2829 to ET. In the intent-to-treat population, with a median follow-up of 76.2 months, abemaciclib–ET resulted in a 15.8% lower risk of death than ET [661 deaths; hazard ratio 0.842, 95% confidence interval (CI) 0.722-0.981, P = 0.027], meeting the prespecified boundary for significance. The 7-year OS was 86.8% with abemaciclib–ET and 85.0% with ET (absolute difference, 1.8%). OS benefit was consistent across prespecified subgroups. In addition to patients who had already died of metastatic disease, fewer patients in the abemaciclib–ET arm were living with metastatic disease compared with the ET arm (6.4% versus 9.4%). Sustained improvement was demonstrated in IDFS and DRFS (hazard ratio 0.734, 95% CI 0.657-0.820 and hazard ratio 0.746, 95% CI 0.662-0.840, respectively). Seven-year IDFS was 77.4% with abemaciclib–ET and 70.9% with ET (absolute difference, 6.5%) and 7-year DRFS were 80.0% and 74.9% (absolute difference, 5.1%). The long-term safety data compiled did not support any concerns of delayed toxicities.
Conclusions
Adjuvant abemaciclib–ET resulted in a statistically significant and clinically meaningful improvement in OS compared with ET in patients with HR-positive, HER2-negative, node-positive, high-risk EBC. At 7 years, abemaciclib–ET continued to demonstrate a sustained IDFS and DRFS benefit.
{"title":"Overall survival with abemaciclib in early breast cancer☆","authors":"S. Johnston , M. Martin , J. O’Shaughnessy , R. Hegg , S.M. Tolaney , V. Guarneri , L. Del Mastro , M. Campone , J. Sohn , F. Boyle , J. Cortes , H.S. Rugo , M.P. Goetz , E.P. Hamilton , C.-S. Huang , E. Senkus , I. Cicin , L. Testa , P. Neven , J. Huober , N. Harbeck","doi":"10.1016/j.annonc.2025.10.005","DOIUrl":"10.1016/j.annonc.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Adjuvant abemaciclib combined with endocrine therapy (ET) significantly improved invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, node-positive, high-risk early breast cancer (EBC). The impact on overall survival (OS) remained unknown.</div></div><div><h3>Patients and methods</h3><div>In the phase III monarchE trial (NCT03155997), patients received ET for at least 5 years with or without abemaciclib for 2 years. In this article, we report the primary OS results, a key secondary endpoint, and updated estimates of IDFS and distant relapse-free survival (DRFS).</div></div><div><h3>Results</h3><div>Overall, 5637 patients underwent randomization, with 2808 assigned to abemaciclib–ET, and 2829 to ET. In the intent-to-treat population, with a median follow-up of 76.2 months, abemaciclib–ET resulted in a 15.8% lower risk of death than ET [661 deaths; hazard ratio 0.842, 95% confidence interval (CI) 0.722-0.981, <em>P</em> = 0.027], meeting the prespecified boundary for significance. The 7-year OS was 86.8% with abemaciclib–ET and 85.0% with ET (absolute difference, 1.8%). OS benefit was consistent across prespecified subgroups. In addition to patients who had already died of metastatic disease, fewer patients in the abemaciclib–ET arm were living with metastatic disease compared with the ET arm (6.4% versus 9.4%). Sustained improvement was demonstrated in IDFS and DRFS (hazard ratio 0.734, 95% CI 0.657-0.820 and hazard ratio 0.746, 95% CI 0.662-0.840, respectively). Seven-year IDFS was 77.4% with abemaciclib–ET and 70.9% with ET (absolute difference, 6.5%) and 7-year DRFS were 80.0% and 74.9% (absolute difference, 5.1%). The long-term safety data compiled did not support any concerns of delayed toxicities.</div></div><div><h3>Conclusions</h3><div>Adjuvant abemaciclib–ET resulted in a statistically significant and clinically meaningful improvement in OS compared with ET in patients with HR-positive, HER2-negative, node-positive, high-risk EBC. At 7 years, abemaciclib–ET continued to demonstrate a sustained IDFS and DRFS benefit.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 2","pages":"Pages 155-165"},"PeriodicalIF":65.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328035","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 : 2026-02-01Epub Date: 2025-11-04DOI: 10.1016/j.annonc.2025.10.018
J.S. Deutsch , R.A. Scolyer , E. Burton , K.J. Busam , K.Y. Chen , A. Cimino-Mathews , T.R. Cottrell , C.E. de Andrea , P.O. Fiset , G.V. Long , J. Messina , R.V. Rawson , R. Salgado , C.M. Schürch , R.R. Seethala , L.M. Sholl , S. Signoretti , S.L. Topalian , B.A. van de Wiel , X. Xu , J.M. Taube
Background
Practice-changing clinical trials for novel therapeutic regimens administered in the neoadjuvant setting have been reported for multiple cancer types, bringing this treatment strategy to the forefront for patients with high-risk surgically resectable disease. Previously, tumor-type- or therapy-type-specific scoring systems were used for pathologic response assessment. The goal of this effort is to update, harmonize, and standardize the emerging system(s) for pathologic response assessment and data capture.
Materials and methods
Leaders in pathology, oncology, and surgery, including those from the Society for Immunotherapy of Cancer’s Pan-tumor Harmonization of Pathologic Response Assessment (PATHdata) efforts and the International Neoadjuvant Melanoma Consortium (INMC), convened to develop updated consensus guidelines for pathologic response assessment, including specimen handling and tissue submission, scoring, and reporting. This paper builds upon previous recommendations, which are updated based on histologic features associated with patient outcomes. Specific attention was paid to commonalities across tumor types, as well as tumor-type-specific considerations.
Results
A revised and standardized approach to tissue submission is recommended, including total submission of tumors ≤3 cm in size for histologic analysis. Additional guidance is provided for larger tumors. Pathologic response is quantified through assessments of percentage of residual viable tumor (%RVT), necrosis, and regression. Descriptions of histologic features to be scored are provided together with a standardized reporting template. Recommendations regarding collecting additional key datapoints are also made, to allow continued, extended validation of this pan-tumor approach.
Conclusions
As pathologic response emerges as a surrogate endpoint for long-term clinical outcomes and to help inform adaptive adjuvant therapy decisions in routine clinical care, standardization is critical to facilitate consistent and reliable application. This pan-tumor approach to scoring and reporting supports robust stratification of patient outcomes, facilitates comparisons across clinical trials and tumor types, enhances data collection, and establishes a foundation for identifying additional, clinically meaningful %RVT cut points.
{"title":"Updated pan-tumor guidelines for neoadjuvant scoring of pathologic response: a joint SITC and INMC effort","authors":"J.S. Deutsch , R.A. Scolyer , E. Burton , K.J. Busam , K.Y. Chen , A. Cimino-Mathews , T.R. Cottrell , C.E. de Andrea , P.O. Fiset , G.V. Long , J. Messina , R.V. Rawson , R. Salgado , C.M. Schürch , R.R. Seethala , L.M. Sholl , S. Signoretti , S.L. Topalian , B.A. van de Wiel , X. Xu , J.M. Taube","doi":"10.1016/j.annonc.2025.10.018","DOIUrl":"10.1016/j.annonc.2025.10.018","url":null,"abstract":"<div><h3>Background</h3><div>Practice-changing clinical trials for novel therapeutic regimens administered in the neoadjuvant setting have been reported for multiple cancer types, bringing this treatment strategy to the forefront for patients with high-risk surgically resectable disease. Previously, tumor-type- or therapy-type-specific scoring systems were used for pathologic response assessment. The goal of this effort is to update, harmonize, and standardize the emerging system(s) for pathologic response assessment and data capture.</div></div><div><h3>Materials and methods</h3><div>Leaders in pathology, oncology, and surgery, including those from the Society for Immunotherapy of Cancer’s Pan-tumor Harmonization of Pathologic Response Assessment (PATHdata) efforts and the International Neoadjuvant Melanoma Consortium (INMC), convened to develop updated consensus guidelines for pathologic response assessment, including specimen handling and tissue submission, scoring, and reporting. This paper builds upon previous recommendations, which are updated based on histologic features associated with patient outcomes. Specific attention was paid to commonalities across tumor types, as well as tumor-type-specific considerations.</div></div><div><h3>Results</h3><div>A revised and standardized approach to tissue submission is recommended, including total submission of tumors ≤3 cm in size for histologic analysis. Additional guidance is provided for larger tumors. Pathologic response is quantified through assessments of percentage of residual viable tumor (%RVT), necrosis, and regression. Descriptions of histologic features to be scored are provided together with a standardized reporting template. Recommendations regarding collecting additional key datapoints are also made, to allow continued, extended validation of this pan-tumor approach.</div></div><div><h3>Conclusions</h3><div>As pathologic response emerges as a surrogate endpoint for long-term clinical outcomes and to help inform adaptive adjuvant therapy decisions in routine clinical care, standardization is critical to facilitate consistent and reliable application. This pan-tumor approach to scoring and reporting supports robust stratification of patient outcomes, facilitates comparisons across clinical trials and tumor types, enhances data collection, and establishes a foundation for identifying additional, clinically meaningful %RVT cut points.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 2","pages":"Pages 141-154"},"PeriodicalIF":65.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861731","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 : 2026-02-01Epub Date: 2026-01-19DOI: 10.1016/j.annonc.2025.12.016
H. Tawbi , D. Massi
{"title":"Optimizing pathological response assessment after neoadjuvant immunotherapy: linking clinical practice to drug development","authors":"H. Tawbi , D. Massi","doi":"10.1016/j.annonc.2025.12.016","DOIUrl":"10.1016/j.annonc.2025.12.016","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 2","pages":"Pages 139-140"},"PeriodicalIF":65.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993555","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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