Annals of Oncology最新文献

{"title":"Results from a phase Ib study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small-cell lung cancer (NSCLC) after progression on prior osimertinib","authors":"H. Horinouchi ,&nbsp;B.C. Cho ,&nbsp;D.R. Camidge ,&nbsp;K. Goto ,&nbsp;P. Tomasini ,&nbsp;Y. Li ,&nbsp;A. Vasilopoulos ,&nbsp;P. Brunsdon ,&nbsp;D. Hoffman ,&nbsp;W. Shi ,&nbsp;E. Bolotin ,&nbsp;V. Blot ,&nbsp;J. Goldman","doi":"10.1016/j.annonc.2025.01.001","DOIUrl":"10.1016/j.annonc.2025.01.001","url":null,"abstract":"<div><h3>Background</h3><div>Osimertinib is the standard first-line treatment for advanced epidermal growth factor receptor <em>(EGFR)</em>-mutated non-small-cell lung cancer (NSCLC). However, treatment resistance is inevitable and increased c-Met protein expression correlates with resistance. Telisotuzumab vedotin (Teliso-V) is an antibody–drug conjugate that targets c-Met protein overexpression. In this article, we report the results of a phase I/Ib trial evaluating Teliso-V plus osimertinib in patients with NSCLC after progression on osimertinib.</div></div><div><h3>Patients and methods</h3><div>This multicenter, open-label study (NCT02099058) enrolled patients with advanced <em>EGFR</em>-mutated, c-Met protein-overexpressing, non-squamous NSCLC that had progressed on prior osimertinib. Patients received Teliso-V (intravenously, every 2 weeks) plus osimertinib (orally, 80 mg once daily). Teliso-V was evaluated at 1.6 mg/kg in a safety lead-in phase and escalated to 1.9 mg/kg. Dose expansion included both doses. Endpoints included safety and tolerability, pharmacokinetics, objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS).</div></div><div><h3>Results</h3><div>A total of 38 patients received Teliso-V (1.6 mg/kg, <em>n</em> = 20; 1.9 mg/kg, <em>n</em> = 18) plus osimertinib and were included in this analysis. No dose-limiting toxicities were observed. Most frequent any-grade treatment-emergent adverse events (TEAEs) were peripheral sensory neuropathy (50%), peripheral edema (32%), and nausea (24%). Most common grade 3/4 TEAEs were anemia (11%) and pulmonary embolism (8%). Five TEAEs led to death; none were reported as being related to Teliso-V or osimertinib. The pharmacokinetic profile of Teliso-V plus osimertinib was similar to Teliso-V monotherapy. After a median follow-up of 7.4 months, the ORR was 50.0% per independent central review (ICR) (DOR not reached), and median PFS per ICR was 7.4 months (95% confidence interval 5.4 months-not reached).</div></div><div><h3>Conclusions</h3><div>Teliso-V plus osimertinib had promising activity and a manageable safety profile in patients with c-Met protein-overexpressing, <em>EGFR</em>-mutated non-squamous NSCLC after progression on osimertinib. This combination has the potential to address an unmet medical need in this patient population.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 5","pages":"Pages 583-591"},"PeriodicalIF":56.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977345","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":"Neo-adjuvant FOLFOX with and without panitumumab for patients with KRAS-wt locally advanced colon cancer: results following an extended biomarker panel on the FOxTROT trial embedded phase II population☆","authors":"J.F. Seligmann ,&nbsp;D. Morton ,&nbsp;F. Elliott ,&nbsp;K. Handley ,&nbsp;R. Gray ,&nbsp;M. Seymour ,&nbsp;B. Glimelius ,&nbsp;L. Magill ,&nbsp;C.J.M. Williams ,&nbsp;P. Quirke ,&nbsp;D. Bottomley ,&nbsp;H.M. Wood ,&nbsp;K. Murakami ,&nbsp;A.D. Beggs ,&nbsp;N.P. West ,&nbsp;FOxTROT Collaborative Group","doi":"10.1016/j.annonc.2024.12.013","DOIUrl":"10.1016/j.annonc.2024.12.013","url":null,"abstract":"<div><h3>Background</h3><div>The FOxTROT trial has reported advantages of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). In this article, we present results of the embedded randomised phase II trial testing the addition of panitumumab to neoadjuvant FOLFOX compared with FOLFOX alone in <em>RAS</em> and <em>BRAF</em>-wild-type (wt) patients and with biomarker hyperselection.</div></div><div><h3>Patients and methods</h3><div>Patients had operable, computed tomography-predicted stage T3-4, N0-2, M0 colon adenocarcinoma. <em>KRAS</em>-wt patients allocated to NAC could optionally be sub-randomised 1 : 1 to FOLFOX ± panitumumab during the preoperative phase. <em>RAS</em>/<em>BRAF</em> were tested by next-generation sequencing; and epiregulin (<em>EREG</em>)/amphiregulin (<em>AREG</em>) by RNAseq. The primary endpoint was time to recurrence (TTR) in <em>RAS</em>/<em>BRAF</em>-wt patients; secondary endpoints included safety, histological down-staging, disease-free survival (DFS), colon cancer-specific survival (CCSS), overall survival (OS) and impact of primary tumour location and <em>EREG</em>/<em>AREG</em>.</div></div><div><h3>Results</h3><div>In total 269 <em>KRAS</em>-wt patients were enrolled into the embedded phase II trial. Extended <em>RAS</em>/<em>BRAF</em> data were available for 232 (83%) patients; 22/232 (9.5%) were <em>RAS</em>-mutant; 41/210 (20%) were <em>BRAF</em>-mutant. Median follow-up was 42 months. In 169 <em>RAS</em>/<em>BRAF</em>-wt patients, there was a trend towards reduced recurrences with FOLFOX plus panitumumab compared with FOLFOX (12% versus 21%, hazard ratio = 0.51, <em>P</em> = 0.09); significant improvements were seen for DFS, CCSS and OS. Within the hyperselected <em>EREG</em>/<em>AREG</em>-high group, there was significant reduction in recurrences with panitumumab. Panitumumab was not associated with increased pathological regression of the primary tumour (tumour regression grade 1-3 16% versus 22%, <em>P</em> = 0.27). FOLFOX plus panitumumab was associated with higher rates of grade 3 diarrhoea (8% versus 3%) and rash (22% versus 2%).</div></div><div><h3>Conclusion</h3><div>This exploratory analysis from a randomised phase II study shows a non-significant improvement in TTR from the addition of neoadjuvant panitumumab to perioperative FOLFOX in <em>RAS/BRAF</em>-wt LACC. Hyperselection with <em>EREG</em>/<em>AREG</em> status was associated with increased efficacy. A dedicated prospective trial within a biomarker-selected population is under development.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 5","pages":"Pages 520-528"},"PeriodicalIF":56.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977344","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":"Unveiling targets and resistance in FGFR-altered cancers","authors":"C.B. Westphalen","doi":"10.1016/j.annonc.2025.01.002","DOIUrl":"10.1016/j.annonc.2025.01.002","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 359-360"},"PeriodicalIF":56.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969363","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":"Is the abundance of B cells the best biomarker to predict immune checkpoint inhibitor response in head and neck squamous cell cancers?","authors":"J.L. Low ,&nbsp;W.Q. Chong ,&nbsp;B.C. Goh","doi":"10.1016/j.annonc.2025.01.003","DOIUrl":"10.1016/j.annonc.2025.01.003","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 3","pages":"Pages 238-239"},"PeriodicalIF":56.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969360","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":"Subcutaneous versus intravenous nivolumab for renal cell carcinoma☆","authors":"L. Albiges ,&nbsp;M.T. Bourlon ,&nbsp;M. Chacón ,&nbsp;H.J. Cutuli ,&nbsp;Y.A.L. Chuken ,&nbsp;B. Żurawski ,&nbsp;J.M. Mota ,&nbsp;I. Magri ,&nbsp;M. Burotto ,&nbsp;M. Luz ,&nbsp;J. de Menezes ,&nbsp;E.P.Y. Ruiz ,&nbsp;S. Fu ,&nbsp;M. Richardet ,&nbsp;B.P. Valderrama ,&nbsp;M. Maruzzo ,&nbsp;S. Bracarda ,&nbsp;M. Breckenridge ,&nbsp;H.E. Vezina ,&nbsp;D. Rathod ,&nbsp;S. George","doi":"10.1016/j.annonc.2024.09.002","DOIUrl":"10.1016/j.annonc.2024.09.002","url":null,"abstract":"<div><h3>Background</h3><div>The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and health care efficiencies.</div></div><div><h3>Patients and methods</h3><div>CheckMate 67T (NCT04810078) was a phase III, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20 000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). The primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis [time-averaged serum concentration over the first 28 days (C_avgd28), and minimum steady-state serum concentration (C_minss); noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios (GMR) ≥0.8]. Objective response rate (ORR) was a key secondary endpoint powered for noninferiority [noninferiority threshold: lower boundary of 95% CI of relative risk of ORR (subcutaneous versus intravenous nivolumab) ≥0.60].</div></div><div><h3>Results</h3><div>Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of C_avgd28 and C_minss was 2.098 (90% CI 2.001-2.200) and 1.774 (90% CI 1.633-1.927), respectively. After 8 months of minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI 19.0%-30.0%) versus 18.2% with intravenous nivolumab [95% CI 13.6%-23.6%; relative risk: 1.33 (95% CI 0.94-1.87)]. Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar.</div></div><div><h3>Conclusions</h3><div>Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 99-107"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269727","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":"Reply to Letter to the Editor “Optimising Treatment Strategies in Metastatic Colorectal Cancer: Insights from CAIRO4” by Güzel et al.","authors":"J.H.W. de Wilt ,&nbsp;D.E.W. van der Kruijssen ,&nbsp;M. Koopman","doi":"10.1016/j.annonc.2024.10.003","DOIUrl":"10.1016/j.annonc.2024.10.003","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 122-124"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581921","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":"THANKS TO REFEREES 2024","authors":"","doi":"10.1016/j.annonc.2024.11.005","DOIUrl":"10.1016/j.annonc.2024.11.005","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 1-2"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143138771","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":"Tocilizumab provides dual benefits in treating immune checkpoint inhibitor-associated arthritis and preventing relapse during ICI rechallenge: the TAPIR study","authors":"P.-F. Petit ,&nbsp;D. Daoudlarian ,&nbsp;S. Latifyan ,&nbsp;H. Bouchaab ,&nbsp;N. Mederos ,&nbsp;J. Doms ,&nbsp;K. Abdelhamid ,&nbsp;N. Ferahta ,&nbsp;L. Mencarelli ,&nbsp;V. Joo ,&nbsp;R. Bartolini ,&nbsp;A. Stravodimou ,&nbsp;K. Shabafrouz ,&nbsp;G. Pantaleo ,&nbsp;S. Peters ,&nbsp;M. Obeid","doi":"10.1016/j.annonc.2024.08.2340","DOIUrl":"10.1016/j.annonc.2024.08.2340","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this retrospective study was to evaluate the dual efficacy of tocilizumab (TCZ) in the treatment of immune checkpoint inhibitor (ICI)-associated arthritis (ICI-AR) and the prevention of relapses after rechallenge.</div></div><div><h3>Patients and methods</h3><div>We identified 26 patients with ICI-AR. The primary objectives were to evaluate TCZ efficacy in ICI-AR treatment and as secondary prophylaxis during ICI rechallenge in 11 of them. Patients received prednisone (CS) at 0.3 mg/kg tapered at 0.05 mg/kg weekly for six weeks. TCZ was administered at a dose of 8 mg/kg every 2 weeks. In the subgroup receiving secondary prophylaxis (rechallenge <em>n</em> = 11), TCZ was reintroduced with the same regimen concurrently with ICI rechallenge, and without the addition of CS. A control group of patients (rechallenge <em>n</em> = 5) was rechallenged without TCZ. Secondary endpoints included post-rechallenge evaluation of ICI duration, reintroduction of CS &gt;0.1 mg/kg/day, ICI-AR flares, and disease control rate.</div></div><div><h3>Results</h3><div>The median age of the patients was 70 years. The median follow-up from ICI initiation was 864 days. Among the 20 patients treated with TCZ for ICI-AR, all (100%) achieved an ACR70 response rate, defined as greater than 70% improvement, at 10 weeks. Some 81% of these patients achieved steroid-free remission after 24 weeks on TCZ. The median follow-up period was 552 days in rechallenged patients. The results demonstrated a reduction in ICI-AR relapses upon ICI rechallenge in patients receiving TCZ prophylaxis compared with patients who did not receive prophylaxis (17% versus 40%). The requirement for CS was completely abolished with prophylaxis (0% versus 20%), and the mean duration of ICI treatment was notably extended from 113 to 206 days. The 12-month post-rechallenge outcomes showed a disease control rate of 77%. During TCZ prophylaxis, CXCL9 remained elevated, showing no decline from their concentrations at the onset of ICI-AR.</div></div><div><h3>Conclusions</h3><div>In addition to treating ICI-AR, TCZ demonstrated efficacy as a secondary prophylactic agent, preventing the recurrence of symptoms and lengthening ICI treatment duration after ICI rechallenge.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 43-53"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144991","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":"A randomized, double-blind, placebo-controlled phase II study of olanzapine-based prophylactic antiemetic therapy for delayed and persistent nausea and vomiting in patients with HER2-positive or HER2-low breast cancer treated with trastuzumab deruxtecan: ERICA study (WJOG14320B)☆","authors":"H. Sakai ,&nbsp;J. Tsurutani ,&nbsp;Y. Ozaki ,&nbsp;H. Ishiguro ,&nbsp;K. Nozawa ,&nbsp;T. Yamanaka ,&nbsp;K. Aogi ,&nbsp;K. Matsumoto ,&nbsp;T. Iwasa ,&nbsp;M. Tokiwa ,&nbsp;M. Tsuneizumi ,&nbsp;Y. Miyoshi ,&nbsp;C. Kitagawa ,&nbsp;M. Yamamoto ,&nbsp;Y. Takano ,&nbsp;C.K. Imamura ,&nbsp;Y. Chiba ,&nbsp;D. Takiguchi ,&nbsp;T. Ezumi ,&nbsp;T. Takano","doi":"10.1016/j.annonc.2024.09.001","DOIUrl":"10.1016/j.annonc.2024.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Nausea and vomiting are common adverse events associated with trastuzumab deruxtecan (T-DXd). We evaluated the efficacy of an olanzapine-based triplet regimen for preventing nausea and vomiting in patients receiving their first cycle T-DXd.</div></div><div><h3>Patients and methods</h3><div>This multi-institutional, randomized, double-blind, placebo-controlled (ERICA) phase II study enrolled patients with human epidermal growth factor receptor 2-positive/human epidermal growth factor receptor 2-low metastatic breast cancer receiving their first cycle of T-DXd. Patients were randomized to olanzapine 5 mg or placebo once daily (1 : 1 ratio) from day 1 to day 6, plus a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone 6.6 mg intravenously or 8 mg orally on day 1. The total observation period was 504 h (21 days) from the first T-DXd administration. The primary endpoint was complete response (CR), defined as no emetic events and no rescue medications, in the delayed phase (24-120 h after T-DXd), with the type I error rate of 0.2 (one-sided) for the comparison. Secondary endpoints included no nausea rate in the delayed and persistent phases (120-504 h), adverse event by Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported outcomes version of the CTCAE (PRO-CTCAE).</div></div><div><h3>Results</h3><div>In total, 168 patients were enrolled at 43 sites in Japan (November 2021-September 2023) with 162 patients (olanzapine, <em>n</em> = 80; placebo, <em>n</em> = 82) included in the per protocol set. The primary endpoint was met as the delayed phase CR rate was significantly greater with olanzapine than placebo (70.0% versus 56.1%, <em>P</em> = 0.047). Efficacy was maintained in the persistent phase (63.9% versus 44.4%). No nausea rate was also greater with olanzapine (delayed phase: 57.5% versus 37.8%; persistent phase: 51.4% versus 31.9%). CR rates in the delayed phase favored olanzapine across subgroups. Appetite loss was also decreased with olanzapine. Hyperglycemia and somnolence were mostly of low-grade severity.</div></div><div><h3>Conclusion</h3><div>Olanzapine 5 mg for 6 days with 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone appears effective for T-DXd-treated patients to prevent delayed and persistent nausea and vomiting.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 31-42"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279652","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":"Clinical validation of a tissue-agnostic genome-wide methylome enrichment molecular residual disease assay for head and neck malignancies☆","authors":"G. Liu ,&nbsp;S.H. Huang ,&nbsp;L. Ailles ,&nbsp;K. Rey-McIntyre ,&nbsp;C.A. Melton ,&nbsp;S.Y. Shen ,&nbsp;J.M. Burgener ,&nbsp;B. Brown ,&nbsp;J. Zhang ,&nbsp;J. Min ,&nbsp;Y. Wang ,&nbsp;O. Hall ,&nbsp;J.T. Jones ,&nbsp;K. Budhraja ,&nbsp;J.B. Provance ,&nbsp;E.V. Sosa ,&nbsp;A. Licon ,&nbsp;A. Williams ,&nbsp;S.V. Bratman ,&nbsp;B.A. Allen ,&nbsp;D.D. De Carvalho","doi":"10.1016/j.annonc.2024.08.2348","DOIUrl":"10.1016/j.annonc.2024.08.2348","url":null,"abstract":"<div><h3>Background</h3><div>Outcomes for patients with locally advanced head and neck cancer (HNC) treated with curative intent remain disappointing, with 5-year survival rates at 50%. Most recurrences occur within the first 2 years after treatment, providing a window of opportunity to identify patients with molecular residual disease (MRD). A tissue-agnostic test for MRD detection in patients with human papillomavirus (HPV) positive and negative HNC, where tissue is often scarce, is needed.</div></div><div><h3>Patients and methods</h3><div>Patients with stage I-IVB HNC, including patients positive and negative for HPV, were enrolled and peripheral blood plasma was collected longitudinally at diagnosis and ∼3, 12, and 24 months after curative intent treatment. The full cohort includes 325 patients with 1155 samples. Samples were split into distinct sets to train and validate a classifier capable of identifying MRD using a tissue-agnostic genome-wide methylome enrichment platform. The primary endpoint was recurrence-free survival (RFS).</div></div><div><h3>Results</h3><div>With a median follow-up of 60 months, patients in the blinded validation set with MRD positivity experienced significantly worse RFS with a hazard ratio (HR) of 35.7 [95% confidence interval (CI) 10.8-117.8; <em>P</em> &lt; 0.0001]. For patients with HPV negativity, HR was 42.3 (95% CI 9.8-182.3; <em>P</em> &lt; 0.0001); for patients with HPV-positive oropharyngeal cancer, HR was 24.1 (95% CI 3.0-196.8; <em>P</em> &lt; 0.0001). Moreover, the lead time between MRD positivity and clinical recurrence was up to 14.9 months, with a mean lead time of 4.1 months. Surveillance sensitivity was 91% (95% CI 77% to 97%) and specificity was 88% (95% CI 80% to 93%).</div></div><div><h3>Conclusions</h3><div>Here we validate the clinical performance characteristics of a tissue-agnostic genome-wide methylome enrichment assay for MRD detection in patients with HNC. The MRD detection test showed high sensitivity for identifying recurrence at high specificity across different anatomical sites, HPV status, and treatment regimens, highlighting the broad applicability for MRD detection in patients with HNC.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 108-117"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399192","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}