ESMO Open最新文献

{"title":"Genomic landscape, immune microenvironment and survival in male versus female breast cancer☆","authors":"D. Trapani ,&nbsp;S.K. Deshmukh ,&nbsp;T. Samec ,&nbsp;S. Wu ,&nbsp;J. Xiu ,&nbsp;P. Walker ,&nbsp;D.L. Abravanel ,&nbsp;P. Advani ,&nbsp;P.M. Spanheimer ,&nbsp;N.U. Lin ,&nbsp;G. Curigliano ,&nbsp;S.L. Graff ,&nbsp;M. Lustberg ,&nbsp;G.W. Sledge ,&nbsp;S.M. Tolaney ,&nbsp;J.P. Leone","doi":"10.1016/j.esmoop.2026.106059","DOIUrl":"10.1016/j.esmoop.2026.106059","url":null,"abstract":"<div><h3>Background</h3><div>Male breast cancer (MaBC) represents ∼1% of breast malignancies and may have significant differences to female BC (FeBC) that impact prognosis and treatment response. In this work, we sought to characterize the molecular and immune landscape of MaBC.</div></div><div><h3>Materials and methods</h3><div>We analyzed whole-transcriptome (WTS) and whole exome sequencing from 19 697 deidentified tumor samples provided to Caris Life Sciences.</div></div><div><h3>Results</h3><div>Our study found significant sex-based differences in the molecular and immunological landscape within each tumor subtype between MaBC and FeBC, including increased M2 Mϕ, and decreased dendritic cells and immune-related gene expression. Genetic amplifications and mutation frequency differences between MaBC and FeBC across molecular subtypes included significant differences in <em>TP53</em> and <em>ESR1</em> mutation [2.4% versus 31.2%; 5.8% versus 13.3%, hormone receptor (HR)-positive/HER2-negative], and <em>BRCA2</em> and <em>CDH1</em> mutation [6.7% versus 2.1%, HER2-positive; 16.7% versus 5.6%, triple-negative breast cancer (TNBC)]. Immunologically, MaBC exhibited increased tumor-promoting M2 Mϕ (5.8% versus 3.0%, TNBC), decreased dendritic cell infiltration (2.2% versus 2.6%, HR-positive/HER2-negative) and decreased <em>PDCD1</em> and <em>LAG3</em> immune checkpoint gene expression (0.3% versus 0.4%; 2.3% versus 2.9%, HR-positive/HER2-negative) against FeBC.</div></div><div><h3>Conclusions</h3><div>Our findings suggest a unique genomic and immunologic landscape in MaBC requiring a sex-informed approach and provide candidate therapeutic targets and mechanisms of resistance.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 3","pages":"Article 106059"},"PeriodicalIF":8.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world external control arm for the single-arm LIBRETTO-001 trial of selpercatinib in RET-mutation-positive medullary thyroid cancer: RECALIB-RET","authors":"J. Hadoux ,&nbsp;J. Hernando ,&nbsp;K.H. Wong ,&nbsp;C. Do Cao ,&nbsp;H. Lasolle ,&nbsp;C. Buffet ,&nbsp;D. Benisvy ,&nbsp;F. Illouz ,&nbsp;O. Schneegans ,&nbsp;R. Varnier ,&nbsp;D. Drui ,&nbsp;S. Zanetta ,&nbsp;S. Hescot ,&nbsp;M. Muller ,&nbsp;C. Nascimento ,&nbsp;N. Roudaut ,&nbsp;M. Khanal ,&nbsp;S. Zheng ,&nbsp;X. Li ,&nbsp;R. Singh ,&nbsp;G. Segall","doi":"10.1016/j.esmoop.2026.106083","DOIUrl":"10.1016/j.esmoop.2026.106083","url":null,"abstract":"<div><h3>Background</h3><div>The single-arm phase I/II LIBRETTO-001 trial demonstrated durable efficacy with selpercatinib in patients with rearranged during transfection (<em>RET</em>)-mutation-positive medullary thyroid cancer (MTC). RECALIB-RET compared effectiveness outcomes using a real-world external control (EC) arm of patients with <em>RET</em>-mutation-positive MTC treated with standard of care (SoC) versus selpercatinib (LIBRETTO-001).</div></div><div><h3>Patients and methods</h3><div>In this retrospective study, the selpercatinib arm comprised first-line (1L) or second-and-later-line (≥2L) patients from LIBRETTO-001. The EC arm comprised SoC-treated patients, pooled across (i) the French ENDOCAN-TUTHYREF (Refractory Thyroid Tumours) database (1L and ≥2L); (ii) a chart review of European patient medical records (1L and ≥2L) and (iii) a published United States chart review (≥2L). Index treatment was cabozantinib or vandetanib (1L) and any SoC (≥2L; including multikinase inhibitor, chemotherapy or immunotherapy). The primary endpoint was progression-free survival (PFS). The safety profile of SoC in the EC arm was a secondary endpoint. Propensity score matching (PSM) balanced baseline characteristics between treatment arms.</div></div><div><h3>Results</h3><div>Baseline characteristics of the 1L selpercatinib (<em>n</em> = 116) and EC (<em>n</em> = 107) arms were balanced; PSM reduced the sample size by &lt;30% across arms (<em>n</em> = 84 per arm after PSM). 1L selpercatinib conferred statistically significant PFS benefit over SoC both pre-PSM [median: not reached (NR) versus 24.0 months; <em>P</em> &lt; 0.001] and post-PSM (median: NR versus 26.1 months; <em>P</em> &lt; 0.001). In ≥2L (selpercatinib, <em>n</em> = 179; EC, <em>n</em> = 51), PSM increased attrition, reducing sample sizes by 78.8% (selpercatinib) and 25.5% (EC), to <em>n</em> = 38 per arm. The unadjusted median PFS was significantly longer with ≥2L selpercatinib versus SoC (35.6 months versus 11.6 months; <em>P</em> = 0.005); the difference did not reach significance after PSM. Safety findings were consistent with previously reported findings for SoC.</div></div><div><h3>Conclusion</h3><div>Selpercatinib conferred significant PFS benefit over SoC in treatment-naïve (1L) patients with <em>RET</em>-mutation-positive MTC, with inconclusive results in the ≥2L setting. Matching retrospective real-world data to prospective trial data is feasible. EC arms to single-arm trials may provide evidence supporting the evaluation of comparative effectiveness.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 3","pages":"Article 106083"},"PeriodicalIF":8.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II study of magrolimab combination therapies in patients with head and neck squamous-cell carcinoma","authors":"A.D. Colevas ,&nbsp;V. Chin ,&nbsp;J.J. Park ,&nbsp;D. Adkins ,&nbsp;M. Phan ,&nbsp;B. Fang ,&nbsp;F. Forget ,&nbsp;J. Amorim ,&nbsp;K. Misiukiewicz ,&nbsp;D. Alpuim Costa ,&nbsp;N. Rainey ,&nbsp;C. Even ,&nbsp;D.J. Wong ,&nbsp;K. Kerrigan ,&nbsp;Y. Zhang ,&nbsp;M. Dong ,&nbsp;R. Rong ,&nbsp;K. Caldwell ,&nbsp;C. Leung ,&nbsp;J. Dinis","doi":"10.1016/j.esmoop.2026.106085","DOIUrl":"10.1016/j.esmoop.2026.106085","url":null,"abstract":"<div><h3>Background</h3><div>The phase II ELEVATE HNSCC study evaluated magrolimab combinations in metastatic head and neck squamous-cell carcinoma (mHNSCC).</div></div><div><h3>Patients and methods</h3><div>Eligible patients had previously untreated recurrent/mHNSCC (untreated cohort) or pretreated advanced/mHNSCC (pretreated cohort). Safety run-in (SRI) evaluations were followed by phase II assessments. In the SRI, the untreated cohort received magrolimab (M), pembrolizumab (Pem), and platinum/5-fluorouracil (PF) chemotherapy (MPemPF). In phase II, this cohort was randomized to MPemPF, PemPF, or M plus zimberelimab (Zim) and PF (MZimPF). The pretreated cohort received magrolimab plus docetaxel (MDtx; SRI and phase II). SRI primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase II primary endpoints were progression-free survival (PFS; untreated recurrent/mHNSCC) and objective response rate (ORR; pretreated advanced/mHNSCC).</div></div><div><h3>Results</h3><div>No DLTs occurred in the SRIs. In phase II, median PFS in the untreated cohort was 5.5 months with MPemPF (52 patients) versus 5.6 months with PemPF (54 patients; hazard ratio 1.314, 95% confidence interval 0.809-2.136). ORR was 12.2% in the pretreated cohort (41 patients). Grade 3-4 AE rates were 88.5% (MPemPF), 71.7% (PemPF), and 85.4% (MDtx). Across cohorts, 12 fatal AEs occurred (none magrolimab-related).</div></div><div><h3>Conclusions</h3><div>There was no benefit observed with magrolimab treatment. The study closed prematurely, limiting interpretation.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 3","pages":"Article 106085"},"PeriodicalIF":8.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant immune checkpoint inhibitors for localized dMMR/MSI-H gastric cancer: a meta-analysis","authors":"W.K. Schwengber ,&nbsp;R.A. Pereira ,&nbsp;L.F. Leite da Silva ,&nbsp;M. Tumelero ,&nbsp;G. Lenz ,&nbsp;I. Michelon ,&nbsp;K. Chung ,&nbsp;P.L.S. Uson Junior ,&nbsp;T. Bekaii-Saab ,&nbsp;C. de la Fouchardière ,&nbsp;M.B. Sonbol","doi":"10.1016/j.esmoop.2026.106066","DOIUrl":"10.1016/j.esmoop.2026.106066","url":null,"abstract":"<div><h3>Background</h3><div>Early studies indicate that neoadjuvant immune checkpoint inhibitors (ICIs) induce high rates of tumor regression in localized deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) gastric and gastroesophageal junction (GEJ) cancers, raising interest in nonoperative management (NOM). Most available data, however, come from small, nonrandomized cohorts. A systematic synthesis was undertaken to better characterize efficacy and safety outcomes.</div></div><div><h3>Materials and methods</h3><div>A systematic search of PubMed, EMBASE, Scopus, Web of Science, and Cochrane Reviews was conducted from inception through June 2025 for prospective or retrospective studies of neoadjuvant ICIs in localized dMMR/MSI-H gastric or GEJ cancers reporting at least one prespecified outcome. Two reviewers independently extracted data and assessed study quality according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pooled estimates were calculated using a DerSimonian and Laird random-effects model, and NOM outcomes were qualitatively summarized.</div></div><div><h3>Results</h3><div>Twenty studies (396 patients) met inclusion criteria; three used dual ICI therapy, and the remainder used ICI alone or with chemotherapy. Overall, 320 patients (81.0%) underwent surgical resection. The pooled pathologic complete response (pCR) rate was 41.9% [95% confidence interval (CI) 33.2% to 51.1%], clinical complete response 63.8% (95% CI 45.6% to 78.8%), major pathologic response 64.2% (95% CI 49.1% to 76.9%), and grade 3-4 immune-related adverse events 6.7% (95% CI 1.7% to 13.8%). pCR was higher with treatment duration ≥3 months compared with &lt;3 months [50.2% (95% CI 42.3% to 58.7%) versus 28.4% (95% CI 18.9% to 40.2%), χ² = 8.84, <em>P</em> = 0.003]. Forty-four patients were managed nonoperatively, with two early local regrowths at median follow-up ranging from 11.5 to 28 months.</div></div><div><h3>Conclusions</h3><div>Neoadjuvant ICIs are associated with favorable efficacy and safety in localized dMMR/MSI-H gastric and GEJ cancers. Longer neoadjuvant exposure (≥3 months) may improve pCR rates. Larger prospective studies are needed to define optimal treatment duration and the role of organ-preserving strategies such as NOM.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 3","pages":"Article 106066"},"PeriodicalIF":8.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIGNIFIED: whole-body MRI screening in Li–Fraumeni syndrome in the UK","authors":"E. Finn ,&nbsp;A. Sohaib ,&nbsp;S.J. Withey ,&nbsp;S. Sardo Infirri ,&nbsp;C. Bunce ,&nbsp;C.S. Clarke ,&nbsp;J.Y. Weng ,&nbsp;E. Scurr ,&nbsp;R.W. Lee ,&nbsp;R. Eeles ,&nbsp;A. George","doi":"10.1016/j.esmoop.2025.106045","DOIUrl":"10.1016/j.esmoop.2025.106045","url":null,"abstract":"<div><h3>Background</h3><div>Li–Fraumeni syndrome (LFS), caused by a pathogenic germline variant of the <em>TP53</em> tumour suppressor gene, is an autosomal dominant condition that predisposes affected individuals to multiple cancers at a young age. International guidelines recommend yearly screening to identify cancers: in addition to annual breast magnetic resonance imaging (MRI) in female patients and full dermatological skin check, patients should undergo whole-body imaging. Whole-body MRI (WB-MRI) can image from vertex to toes in a single examination, without the use of ionising radiation. We aimed to assess the utility of WB-MRI in detecting malignancies in LFS patients.</div></div><div><h3>Materials and methods</h3><div>SIGNIFIED was a prospective, exploratory and observational study. Patients with LFS were identified and invited to undergo two WB-MRIs 12 months apart. WB-MRI was carried out at 1.5 T from vertex to toes without contrast, including axial T1-, T2- and diffusion-weighted imaging. Images were reviewed independently by two experienced oncological radiologists. Suspicious lesions and incidental findings were discussed in a multidisciplinary meeting, with further investigation and management carried out on a case-by-case basis.</div></div><div><h3>Results</h3><div>Between July 2022 and August 2023, 54 individuals (14 males, 40 females) with LFS underwent a baseline WB-MRI within the study. Fifty patients had a second scan ∼12 months later. Following the first WB-MRI, nine patients underwent biopsy/excision (16.7%), and four cancers were diagnosed (7.4%). Five patients developed interval cancer between the first and second WB-MRI. These were either outside of the initial WB-MRI field of view (i.e. upper limb sarcoma, breast carcinoma) or had developed clinically since the initial scan. Six patients (12%) were diagnosed with a cancer following the second WB-MRI. Seven (70%) out of the 10 cancers detected overall by both scans were in an early stage, and the remaining 3 (30%) were locally advanced or metastatic.</div></div><div><h3>Conclusion</h3><div>WB-MRI can identify early cancers in the high-risk setting of LFS screening, with cancers detected at both baseline and 12-month follow-up screenings. The burden of additional investigations for incidental findings decreases with repeat imaging.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 3","pages":"Article 106045"},"PeriodicalIF":8.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surrogate endpoints for survival in KEYNOTE-585: neoadjuvant/adjuvant pembrolizumab plus chemotherapy versus placebo plus chemotherapy for gastric or gastroesophageal junction adenocarcinoma☆","authors":"K. Shitara ,&nbsp;Y.-J. Bang ,&nbsp;L.S. Wyrwicz ,&nbsp;S.Y. Rha ,&nbsp;T. Oshima ,&nbsp;F. Pietrantonio ,&nbsp;Y.-K. Park ,&nbsp;S. Lonardi ,&nbsp;P. Yañez ,&nbsp;C.-J. Yen ,&nbsp;J.-P. Metges ,&nbsp;M. Garrido ,&nbsp;M. Moehler ,&nbsp;S. Pelles-Avraham ,&nbsp;W.P. Yong ,&nbsp;A. Spallanzani ,&nbsp;E. Jensen ,&nbsp;R. Krishnan ,&nbsp;C.-S. Shih ,&nbsp;S.-E. Al-Batran","doi":"10.1016/j.esmoop.2026.106090","DOIUrl":"10.1016/j.esmoop.2026.106090","url":null,"abstract":"<div><h3>Background</h3><div>In the randomized phase III KEYNOTE-585 trial, neoadjuvant/adjuvant pembrolizumab plus chemotherapy was not superior to placebo plus chemotherapy for event-free survival (EFS) in participants with locally advanced gastric or gastroesophageal (GEJ) adenocarcinoma. However, pembrolizumab plus chemotherapy significantly improved pathologic complete response (pCR) versus placebo plus chemotherapy (difference 10.9%, 95% confidence interval (CI) 7.5% to 14.8%, <em>P</em> &lt; 0.00001). This <em>post hoc</em> analysis evaluated whether pCR, major pathologic response (mPR), and pathologic downstaging (pDS) after neoadjuvant/adjuvant pembrolizumab plus chemotherapy are associated with improved survival outcomes.</div></div><div><h3>Patients and methods</h3><div>Eligible participants had untreated, locally advanced gastric or GEJ adenocarcinoma (including Siewert type 2 or 3) and were scheduled for surgery after preoperative chemotherapy. The main cohort received pembrolizumab or placebo plus chemotherapy [cisplatin plus capecitabine (XP) or cisplatin plus 5-fluorouracil (FP)], whereas the safety cohort received pembrolizumab or placebo plus docetaxel, oxaliplatin, 5-fluorouracil, and leucovorin (FLOT). The outcomes for this <em>post hoc</em> analysis were the relationship between pCR, mPR, pDS to N0, or any pDS with EFS per RECIST v1.1 (by investigator) and overall survival (OS). We report outcomes in the main and FLOT cohorts combined. The data cut-off date was 9 February 2023.</div></div><div><h3>Results</h3><div>A total of 1007 participants were enrolled and randomly assigned (<em>n</em> = 502, pembrolizumab plus chemotherapy; <em>n</em> = 505, placebo plus chemotherapy); 221 (44.0%) and 172 (34.1%) participants, respectively, had pathologic nodal stage N0. The pCR rate was 13.9% with pembrolizumab plus chemotherapy and 2.8% with placebo plus chemotherapy; mPR rates were 31.5% and 22.2%, respectively. Among participants who experienced mPR (≤10% residual viable tumor), the hazard ratios for EFS and OS were 0.6 (95% CI 0.4-1.0) and 0.7 (95% CI 0.4-1.2), respectively, for pembrolizumab plus chemotherapy compared with placebo plus chemotherapy.</div></div><div><h3>Conclusion</h3><div>These findings suggest a potential association between pCR, mPR, or pDS and survival in patients with locally advanced gastric or GEJ adenocarcinoma, although further validation is needed.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 3","pages":"Article 106090"},"PeriodicalIF":8.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges of neoadjuvant immunotherapy in mismatch repair-deficient/microsatellite-unstable localized colon cancer patients","authors":"M. Karoui ,&nbsp;A. Mariani ,&nbsp;J. Taieb","doi":"10.1016/j.esmoop.2026.106893","DOIUrl":"10.1016/j.esmoop.2026.106893","url":null,"abstract":"<div><div>Despite cumulative evidence on the efficacy and tolerability of neoadjuvant immunotherapy in mismatch repair-deficient (dMMR) colon cancer (CC), it is still hard to draw clear recommendations on its indication in our daily clinical practice. Key clinical trials investigating neoadjuvant or adjuvant immune checkpoint inhibitors (ICIs) in dMMR non-metastatic CC were reviewed. Based on their results, we designed an algorithm in the management of dMMR CC patients. The decision to treat patients with non-metastatic dMMR CC with neoadjuvant or adjuvant ICIs is primarily based on the patient’s clinical status, baseline computed tomography (CT) characteristics of the primary tumor, and the therapeutic objectives.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 3","pages":"Article 106893"},"PeriodicalIF":8.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining the role of selinexor in multiple myeloma: strategic use in a shifting treatment landscape","authors":"F. Gay ,&nbsp;G. Buda ,&nbsp;M.T. Petrucci ,&nbsp;N. Bolli ,&nbsp;M. Cea ,&nbsp;D. Derudas ,&nbsp;S. Mangiacavalli ,&nbsp;V. Montefusco ,&nbsp;E. Antonioli ,&nbsp;G. Barilà ,&nbsp;M. Basso ,&nbsp;P. Bertazzoni ,&nbsp;G. Bertuglia ,&nbsp;R. Bianco ,&nbsp;M. Carlisi ,&nbsp;M.L.D. Giudice ,&nbsp;R.D. Pepa ,&nbsp;F. Fazio ,&nbsp;L. Franceschini ,&nbsp;A. Furlan ,&nbsp;E. Zamagni","doi":"10.1016/j.esmoop.2025.106054","DOIUrl":"10.1016/j.esmoop.2025.106054","url":null,"abstract":"<div><div>The treatment landscape of multiple myeloma (MM) has been revolutionized over the past two decades, leading to unprecedented deep and durable responses, prolonged survival, and improved quality of life. Nonetheless, MM is still an incurable disease, and many patients, especially those with high-risk cytogenetics, renal impairment, or early drug resistance, continue to face poor outcomes. Selinexor, the first-in-class, orally bioavailable selective inhibitor of exportin 1 (XPO1), has shown encouraging results in combination with other agents, and selinexor-based therapy has been approved for the treatment of relapsed/refractory MM, with selinexor–bortezomib–dexamethasone approved for patients with at least one prior line of therapy and selinexor–dexamethasone approved in the later-relapse setting. Notably, selinexor-based combinations have demonstrated consistent efficacy across different subgroups of patients, including those with triple-class refractory disease, renal dysfunction, high-risk cytogenetics, and prior anti-CD38 therapy. We herein provide an overview of selinexor, by describing its mechanism of action, potential interaction with other classes of drugs, novel combinations under investigation, and its role in treatment sequencing, by discussing latest results and potential strategies to mitigate toxicities, increase efficacy, and implement treatment adherence in MM. Overall, selinexor continues to represent a valuable option, especially for patients who are ineligible to receive T-cell-redirecting therapies, or difficult-to-treat patient subgroups, where alternative strategies remain limited. Meanwhile, further data on the use of selinexor-based combinations in different settings are eagerly awaited, to help clarify its role and address persistent unmet clinical needs.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 3","pages":"Article 106054"},"PeriodicalIF":8.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I study of ABM-1310 as monotherapy and in combination with cobimetinib for BRAF-mutated advanced solid tumors: safety, efficacy, and dose expansion","authors":"S.A. Piha-Paul ,&nbsp;M. De La Fuente ,&nbsp;F. Iwamoto ,&nbsp;J.-J. Zhu ,&nbsp;S. Nagpal ,&nbsp;F. Braiteh ,&nbsp;S. Chandra ,&nbsp;Y. Fu ,&nbsp;C. Chen ,&nbsp;Z. Yang ,&nbsp;K.K. Tsai","doi":"10.1016/j.esmoop.2025.106047","DOIUrl":"10.1016/j.esmoop.2025.106047","url":null,"abstract":"<div><h3>Background</h3><div>ABM-1310 is an investigational, orally bioavailable BRAF V600 inhibitor with high blood–brain barrier (BBB) penetration.</div></div><div><h3>Patients and methods</h3><div>This first-in-human, phase I trial evaluated patients with BRAF V600-mutated advanced solid tumors, including brain metastases (≤3 cm) and primary central nervous system (CNS) tumors. Patients received ABM-1310 monotherapy [25-250 mg twice a day (b.i.d.); Parts A/C] or in combination (ABM-1310 : 100-200 mg b.i.d.; cobimetinib 60 mg once a day, days 1-21 of each 28-day cycle; Part B). Primary endpoints included safety, tolerability, and maximum tolerated dose (MTD); secondary endpoints included pharmacokinetic (PK) profile and antitumor activity per RECIST v1.1 or Response Assessment in Neuro-Oncology criteria.</div></div><div><h3>Results</h3><div>Fifty-three patients were enrolled (36 monotherapy, 17 combination). Median age was 55 years; 68% were male, 72% had ≥3 prior treatment lines, 92.5% had BRAF V600E mutations, 75% of patients had received prior BRAF plus MEK inhibitor therapy, and 7.5% had BRAF inhibitor monotherapy. Common tumor types included melanoma (47%), glioblastoma (17%) and thyroid cancer (13%). The most frequent treatment-related adverse events were QT prolongation and rash. Dose-limiting toxicities (DLTs) occurred in 6/37 patients (16.2%), all at doses ≥150 mg. All DLTs involved asymptomatic electrocardiogram QT prolonged, with two cases presenting co-occurring toxicities: one with rash and one with renal failure—establishing the MTD at 200 mg b.i.d. Among 50 efficacy-evaluable patients, the objective response rate (ORR) was 12% and disease control rate (DCR) was 64%. Median progression-free survival was 4.96 months (2.07-8.31) and median overall survival was 24.48 months 11.6-not estimable. In patients with primary CNS tumors (<em>n</em> = 13), ORR was 23.1% and DCR 76.9%. PK analyses showed dose-proportional exposure and moderate accumulation.</div></div><div><h3>Conclusions</h3><div>ABM-1310 showed a favorable safety profile and encouraging intracranial activity. These findings support continued evaluation for CNS tumors and in cancer patients with prior BRAF inhibitor exposure.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 2","pages":"Article 106047"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PP081 Immune-related gene signature dynamics during neoadjuvant chemotherapy in early triple-negative breast cancer","authors":"Ahwon Lee ,&nbsp;Jieun Lee ,&nbsp;Kabsoo Shin","doi":"10.1016/j.esmoop.2025.105968","DOIUrl":"10.1016/j.esmoop.2025.105968","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 ","pages":"Article 105968"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147394367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}