Cancer最新文献

{"title":"Correction to “Efficacy and safety of teclistamab in triple-class exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort”","authors":"","doi":"10.1002/cncr.70342","DOIUrl":"10.1002/cncr.70342","url":null,"abstract":"<p>Martin TG, Mateos M-V, Yi JH, et al. Efficacy and safety of teclistamab in triple-class exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort. <i>Cancer</i>. 2026;e70237. doi:10.1002/cncr.70237</p><p></p><p>We apologize for these errors.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 1 study of berzosertib (M6620, VX-970) in combination with cisplatin and radiation in patients with locally advanced head and neck squamous cell carcinoma (ETCTN 9950)","authors":"Aarti Bhatia MD, MPH,&nbsp;Zhengjia Chen PhD,&nbsp;Yuji Zhang PhD,&nbsp;Justine Yang Bruce MD,&nbsp;Susanne Arnold MD,&nbsp;Varinder Kaur MD,&nbsp;Jonathan W. Riess MD,&nbsp;Moon Fenton MD, PhD,&nbsp;Barbara Burtness MD,&nbsp;Nabil F. Saba MD,&nbsp;Harold Tara MD,&nbsp;Conor E. Steuer MD,&nbsp;Dong M. Shin MD,&nbsp;Garrett Wasp MD, MPH,&nbsp;Thomas H. Davis MD,&nbsp;Malini Patel MD,&nbsp;John C. Schmitz PhD,&nbsp;Priyanka Bhateja MD,&nbsp;Virginia Diavolitsis MD,&nbsp;Dan P. Zandberg MD,&nbsp;Darrion L. Mitchell MD, PhD,&nbsp;Brian F. Kiesel PhD,&nbsp;Charles Kunos MD,&nbsp;Steven D. Gore MD,&nbsp;Michael Carducci MD,&nbsp;Jan H. Beumer PharmD, PhD, DABT,&nbsp;Taofeek K. Owonikoko MD, PhD","doi":"10.1002/cncr.70346","DOIUrl":"10.1002/cncr.70346","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ataxia telangiectasia Rad3-related (ATR) protein kinase regulates DNA damage response and is essential for tumor cell survival. Preclinically, ATR inhibition can sensitize tumor cells to radiation and chemotherapy. The authors conducted a phase 1 trial of berzosertib, a selective ATR inhibitor, in combination with definitive radiation and cisplatin in locally advanced head and neck squamous cell cancers (LA-HNSCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>LA-HNSCC patients received daily radiation (2 Gy per fraction to 70 Gy) and weekly intravenous (iv) cisplatin 40 mg/m². Berzosertib was administered (iv) once weekly, starting with a pharmacokinetic lead-in dose. Three berzosertib dose levels (DL) were tested: 120 mg/m² (DL1), 160 mg/m² (DL2), and 200 mg/m² (DL3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-one of 43 enrolled patients were evaluable for safety and preliminary efficacy assessments. Four patients experienced dose-limiting toxicities (DLTs) in dose-escalation: grade 4 thrombocytopenia (1), grade 4 respiratory failure (1), grade 3 renal injury and hypoxia (1), and inability to receive 90% of the planned radiation dose (1). DL3 was the recommended phase 2 dose, and 15 patients were enrolled at this DL as an expansion cohort. Objective response rates (ORR) in patient cohorts treated with any amount of berzosertib; treated with at least 50% of planned treatment; and in the expansion cohort were 78.8% (26 of 33), 78.8% (26 of 33), and 63.6% (7 of 11), respectively, after excluding eight inevaluable patients without post-treatment imaging assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Berzosertib (200 mg/m² iv weekly) was safe when combined with chemoradiation but did not improve complete response rate in LA-HNSCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12984462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147441987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing molecular residual disease detection in cervical cancer through next-generation sequencing of circulating human papillomavirus DNA","authors":"Kathy Han MD, MSc","doi":"10.1002/cncr.70352","DOIUrl":"10.1002/cncr.70352","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442025","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":"Correction to “Imidazoquinoxaline derivative EAPB0503: A promising drug targeting mutant nucleophosmin 1 in acute myeloid leukemia”","authors":"","doi":"10.1002/cncr.70347","DOIUrl":"10.1002/cncr.70347","url":null,"abstract":"<p>Nabbouh AI, Hleihel RS, Saliba JL, et al. Imidazoquinoxaline derivative EAPB0503: a promising drug targeting mutant nucleophosmin 1 in acute myeloid leukemia. <i>Cancer</i>. 2017;123(9):1662-1673. doi:10.1002/cncr.30515</p><p>In the published article, the GAPDH blots for the KG-1α and MOLM13 extracts in Figure 2E were inaccurately presented due to inadvertent errors during figure preparation. The correct Figure 2 is provided below.</p><p>Figure 2. Corrected.</p><p></p><p>The legend for Figure 2 has also been updated (changes in bold) to clarify that the same GAPDH blots for the OCI-AML3 extracts were used in Figures 2E and 2G:</p><p>Furthermore, the loading controls for the KG-1α and MOLM13 extracts in Figure 3A were inaccurately labelled as “Actin” instead of “GAPDH”. The correct Figure 3 is provided below.</p><p>Figure 3. Corrected.</p><p></p><p>The authors apologize for these errors and for the inconvenience they may have caused.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 phase II trial of gemcitabine, nab-paclitaxel, cisplatin with or without a medically supervised ketogenic diet for patients with metastatic pancreatic cancer","authors":"Gayle S. Jameson MSN, ACNP-BC, AOCN,&nbsp;Denise J. Roe PhD,&nbsp;Erkut Borazanci MD,&nbsp;Diana L. Hanna MD,&nbsp;Caroline G. P. Roberts MD,&nbsp;Meredith S. Pelster MD,&nbsp;Richard C. Frank MD,&nbsp;Angela T. Alistar MD,&nbsp;Alan M. Miller MD, PhD,&nbsp;J. Erin Wiedmeier-Nutor MD, MPH,&nbsp;Sandra D. Algaze MD,&nbsp;Alison R. Zoller MS, RDN,&nbsp;Sarah J. Hallberg DO, MS,&nbsp;Betsy C. Wertheim MS,&nbsp;Keehoon Lee PhD,&nbsp;Derek Cridebring PhD,&nbsp;Joshua D. Rabinowitz MD, PhD,&nbsp;Stephen Gately PhD,&nbsp;Jennifer Keppler MBA,&nbsp;Sunil Sharma MD,&nbsp;Daniel D. Von Hoff MD,&nbsp;Drew W. Rasco MD","doi":"10.1002/cncr.70343","DOIUrl":"10.1002/cncr.70343","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A randomized phase II screening trial of gemcitabine, nab-paclitaxel, and cisplatin with a medically supervised ketogenic diet (MSKD) versus usual diet (non-MSKD) was conducted in patients with treatment-naive metastatic pancreatic ductal adenocarcinoma (PDAC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with untreated metastatic PDAC were randomized 1:1 to MSKD or non-MSKD while receiving gemcitabine, nab-paclitaxel, and cisplatin on days 1 and 8 of a 21-day cycle. The MSKD was guided by a remote health care team and daily ketone (beta-hydroxybutyrate) levels, with goal beta-hydroxybutyrate of 0.5 to 3.0 mM. The primary endpoint was progression-free survival (PFS) using a one-sided alpha level of 0.20. Secondary endpoints included overall survival (OS), safety, and quality of life (QOL). Changes in microbiome were an exploratory endpoint.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Overall, there were 32 evaluable patients. In the MSKD arm, 15 of 16 patients achieved nutritional ketosis; the median proportion of days in ketosis was 39.4%. The median PFS was 8.5 months in MSKD patients and 6.2 months in non-MSKD patients: hazard ratio, 0.53 (95% CI, 0.21–1.37); one-sided <i>p</i> = .096. The median OS was 13.7 months with MSKD and 10.2 months in the non-MSKD arm: hazard ratio, 0.58 (95% CI, 0.25–1.37); one-sided <i>p</i> = .107). All MSKD-related adverse events were grade 1-2. There were no significant differences in grade ≥3 chemotherapy-related adverse events between the arms. MSKD patients had no decline in QOL and had significant enrichment of beneficial taxa in the microbiome (<i>p</i> &lt; .05, log-fold change ≥2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The MSKD is feasible in patients with PDAC and, although not powered for definitive outcomes, shows trends in improved PFS and OS when combined with gemcitabine, nab-paclitaxel, and cisplatin, without added toxicity or detriment to QOL. Larger studies are required to confirm these findings and establish the value of the MSKD in pancreatic cancer treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The landscape of chemotherapy modifications among women treated for stage I–IIIA breast cancer","authors":"Jenna Bhimani MBBS, MPH,&nbsp;Kelli O’Connell MSPH,&nbsp;Victoria S. Blinder MD, MSc,&nbsp;Rachael Burganowski MS,&nbsp;Isaac J. Ergas PhD, MPH, MFA,&nbsp;Grace B. Gallagher MPH,&nbsp;Jennifer J. Griggs MD, MPH,&nbsp;Narre Heon MPA,&nbsp;Sankeerth Jinna MPH,&nbsp;Tatjana Kolevska MD,&nbsp;Yuriy Kotsurovskyy MD,&nbsp;Candyce H. Kroenke ScD, MPH,&nbsp;Cecile A. Laurent MS,&nbsp;Raymond Liu MD,&nbsp;Kanichi G. Nakata PhD,&nbsp;Sonia Persaud MPH,&nbsp;Janise M. Roh MSW, MPH,&nbsp;Emily Valice MPH,&nbsp;Elisa V. Bandera MD, PhD,&nbsp;Erin J. Aiello Bowles MPH,&nbsp;Lawrence H. Kushi ScD,&nbsp;Elizabeth D. Kantor PhD, MPH","doi":"10.1002/cncr.70318","DOIUrl":"10.1002/cncr.70318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In the delivery of cancer care, patients may experience modifications to their intended chemotherapy regimen for reasons such as toxicity, tolerability, and scheduling challenges. Understanding modifications from the intended chemotherapy in the real-world setting of cancer care may affect treatment planning and inferences of real-world treatment effectiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By leveraging data from the Optimal Breast Cancer Chemotherapy Dosing Study, this research studied 12,558 women receiving chemotherapy for primary stage I–IIIA breast cancer at Kaiser Permanente Northern California (2006–2019) and Kaiser Permanente Washington (2004–2015). Modifications in chemotherapy administered from intended, both overall and by regimen, are described. Prevalence ratios (PRs) were calculated for associations between regimen attributes and treatment modifications via generalized linear models of the Poisson family with a log-link function and robust standard errors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intent to receive a guideline-concordant regimen was associated with a lower likelihood of modifications from the intended chemotherapy (vs. non–guideline concordant) (PR, 0.74; 95% CI, 0.69–0.79), as was receiving a dose-dense regimen (vs. non–dose dense) (PR, 0.84; 95% CI, 0.78–0.91). Those receiving any neoadjuvant chemotherapy (vs. adjuvant only) were more likely to have modifications from the intended chemotherapy (PR, 1.29; 95% CI, 1.19–1.41). Increasing numbers of cycles and drugs administered were associated with a higher likelihood of modifications (<i>p</i>_trend &lt; .001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Breast cancer chemotherapy regimens used in the real-world setting were examined. Chemotherapy modifications varied markedly by regimen and by characteristics of the regimen administered. Given that more than one in three women in this cohort did not receive chemotherapy as intended, these novel findings may be informative in treatment planning and for future research assessing real-world treatment effectiveness.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429786","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":"Review of patient-reported outcomes in EMPOWER-Lung 1 in patients with advanced non-small cell lung cancer treated with cemiplimab versus chemotherapy","authors":"David R. Gandara MD,&nbsp;Mahmut Gümüş MD,&nbsp;Saadettin Kilickap MD,&nbsp;Ahmet Sezer MD,&nbsp;Igor Bondarenko MD,&nbsp;Mustafa Özgüroğlu MD,&nbsp;Miranda Gogishvili MD,&nbsp;Eric Yan PhD,&nbsp;Xue Jia MPH,&nbsp;Eric Kim MD,&nbsp;Frank Seebach MD,&nbsp;Ruben G. W. Quek PhD","doi":"10.1002/cncr.70339","DOIUrl":"10.1002/cncr.70339","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patient-reported outcomes (PROs) for cemiplimab monotherapy versus chemotherapy from the EMPOWER-Lung 1 phase 3 clinical trial (ClinicalTrials.gov identifier NCT03088540) in patients who had advanced non-small cell lung cancer with programmed cell death-ligand 1 expression ≥50% were previously reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review article characterizes PRO findings for cemiplimab monotherapy versus chemotherapy overall and in prespecified subgroups of patients from the EMPOWER-Lung 1 clinical trial. Patients were randomly assigned 1:1 to receive either cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy, and multiple PROs, including the European Organization for Research and Treatment of Cancer Quality of Life–Core 30 questionnaire, were administered in the EMPOWER-Lung 1 trial. PRO analyses using mixed model for repeated measures analysis to estimate least-squares mean changes in PRO scores from baseline and Cox proportional hazards models for the time to deterioration using a 10-point threshold have been reported and are summarized herein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Generally, the mixed model for repeated measures analysis of global health status/quality of life (GHS/QoL) significantly favored cemiplimab versus chemotherapy in the overall study population and in prespecified subgroup populations. Statistically significant differences in the overall change from baseline in GHS/QoL favoring cemiplimab versus chemotherapy were observed overall and in multiple subgroups, including patients who had brain metastasis (<i>p</i> = .0110), an Eastern Cooperative Oncology Group performance status of 1 (<i>p</i> = .0017), squamous (<i>p</i> = .0247) and nonsquamous (<i>p</i> = .0073) histology, and patients aged 65 years and older (<i>p</i> = .0069). Statistically significant delays in the time to deterioration favoring cemiplimab were observed in GHS/QoL for the subgroup with programmed cell death-ligand 1 expression ≥90% (<i>p</i> = .0152) and the subgroup younger than 65 years (<i>p</i> = .0195).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, the current data support the GHS/QoL benefit of first-line cemiplimab monotherapy versus chemotherapy overall and in multiple subpopulations of patients with programmed cell death-ligand 1 expression ≥50% advanced non-small cell lung cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12976832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Transmission ratio distortion of germline TP53 variants in Li–Fraumeni syndrome families”","authors":"","doi":"10.1002/cncr.70348","DOIUrl":"10.1002/cncr.70348","url":null,"abstract":"<p>Halpern N, Kventsel I, Strauss G, et al. Transmission ratio distortion of germline <i>TP53</i> variants in Li–Fraumeni syndrome families. <i>Cancer</i>. 2025;e35943. doi:10.1002/cncr.35943</p><p>The author Zehavit Frenkel was unintentionally omitted from the author list. The correct author list is as follows:</p><p>Naama Halpern MD, MBA, MPA^1,2, Iris Kventsel MD³, Gal Strauss MD^1,2, Yehudit Peerless MD¹, Ben Boursi MD, MPH^1,2,4, Michal Yalon MD³, Yael Goldberg MD^2,5, Inbal Kedar MSc⁵, Hagit Shani MD⁶, Zehavit Frenkel PhD³, Eitan Friedman MD^2,7, Rinat Bernstein-Molho MD^1,2,8</p><p>1. The Jusidman Cancer Center, Sheba Medical Center, Ramat Gan, Israel</p><p>2. Faculty of Medical and Health Sciences, School of Medicine, Tel-Aviv University, Tel-Aviv, Israel</p><p>3. Department of Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel</p><p>4. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA</p><p>5. The Recanati Genetics Unit, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel</p><p>6. Preimplantation Genetic Diagnosis Center, Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, Israel</p><p>7. The Meirav High-Risk clinic, Sheba Medical Center, Ramat Gan, Israel</p><p>8. The Suzanne Levy-Gertner Oncogenetics Unit, Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, Israel</p><p>We apologize for this error.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted therapy for DNA damage response and homologous recombination repair defects: The Olaparib Combinations trial","authors":"Deborah B. Doroshow MD, PhD,&nbsp;Geoffrey I. Shapiro MD, PhD,&nbsp;Khanh Do MD,&nbsp;Vicki L. Keedy MD,&nbsp;Haider Mahdi MD,&nbsp;Davendra P. S. Sohal MD, PhD,&nbsp;Navid Hafez MD, PhD,&nbsp;Patricia M. LoRusso DO, PhD (h),&nbsp;Michael Cecchini MD,&nbsp;Jeffrey Sklar MD, PhD,&nbsp;Peter Mortimer PhD,&nbsp;Colin Glover PhD,&nbsp;Jacqueline Moses BA,&nbsp;Juliane M. Jürgensmeier PhD,&nbsp;Joseph P. Eder MD","doi":"10.1002/cncr.70332","DOIUrl":"10.1002/cncr.70332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mutations in genes encoding proteins involved the DNA damage response (DDR) occur in up to 20% of patients with cancer. It is unknown whether poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, alone or in combination with ATR or AKT inhibitors, have histology-agnostic clinical efficacy in tumors with DDR mutations or PI3K/AKT pathway mutations, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Olaparib Combinations (OLAPCO) trial enrolled patients in treatment arms based on next-generation sequencing results. In cohorts 1 and 2, patients with tumors harboring DDR mutations received either the PARP inhibitor olaparib or olaparib and the ATR inhibitor ceralasertib. In cohort 3, patients with tumors with PI3K-AKT pathway alterations or ARID1A mutations received olaparib and capivasertib. The primary end point was overall response rate (ORR) at 16 weeks assessed by the Response Evaluation Criteria in Solid Tumors, version 1.1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-six patients were treated, including 26 on olaparib monotherapy, 24 on olaparib and ceralasertib, and 16 on olaparib and capivasertib. Among all patients treated, the ORR was 6.1% and the clinical benefit rate was 31.2% with a median duration of benefit (DoB) of 11 months. Among seven patients with platinum- and PARP inhibitor-resistant high-grade ovarian serous cancer in the olaparib and ceralasertib arm, one had a partial response and four had stable disease with a median DoB of 10 months. No unexpected toxicities were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study failed to meet its primary end point of ORR. DDR and homologous recombination repair defects are not consistently actionable with olaparib as monotherapy or in combination with other targeted therapies in a histology-agnostic manner.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429783","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":"Patient-reported outcomes in NRG Oncology RTOG 1010: Phase 3 trial evaluating the addition of trastuzumab to trimodality treatment of HER2 overexpressing esophageal adenocarcinoma","authors":"Lisa A. Kachnic MD,&nbsp;Jennifer Moughan MS,&nbsp;Theodore S. Hong MD,&nbsp;Michael G. Haddock MD,&nbsp;Naeem Tahir MD,&nbsp;Harry H. Yoon MD,&nbsp;Dayssy A. Diaz MD,&nbsp;Carryn M. Anderson MD,&nbsp;Samantha A. Seaward MD,&nbsp;Christopher E. Lominska MD,&nbsp;Paul E. O’Brien MD,&nbsp;Yuhchyau Chen MD, PhD,&nbsp;Jonathan C. Salo MD,&nbsp;Alfred D. Christie MD,&nbsp;Jennifer A. Dorth MD,&nbsp;Raid M. Aljumaily MD,&nbsp;Elizabeth M. Gore MD,&nbsp;Kathryn A. Winter MS,&nbsp;Howard P. Safran MD,&nbsp;Benjamin Movsas MD","doi":"10.1002/cncr.70345","DOIUrl":"10.1002/cncr.70345","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>NRG/RTOG 1010 evaluated trastuzumab added to trimodality therapy for HER2+ localized esophageal adenocarcinoma (EAC) management. Secondary PRO objectives assessed improvement in the FACT-Esophageal Cancer Subscale (ECS), version 4, with trastuzumab, and if improved ECS correlated with pathologic complete response (pCR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients were randomized to weekly paclitaxel/carboplatin/radiation (chemoradiation, CRT) followed by surgery ± trastuzumab (CRT + Tras). Disease-free survival (DFS) was the primary end point. The projected PRO sample size of 158 patients, based on an 80% participation rate of the DFS primary endpoint sample size of 197 HER2+ patients, would provide ≥ 89% power to detect ≥25% increase in the proportion of CRT + Tras patients with ECS improvement from baseline to 6–8 weeks post-CRT; one-sided α = 0.05, using a χ² test. Improvement in ECS and its swallowing index (SI) and eating index (EI) was defined as 5-, 2-, and 2-point increases, respectively, from baseline to 6–8 weeks post-CRT. Univariate logistic regression was assessed if pCR was associated with improved ECS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 2010 to 2015, 203 HER2+ patients were randomized and 194 were eligible. Of 171 PRO consenting patients, the ECS was completed by 162 (95%) at baseline, 108 (64%) 6–8 weeks, 82 (49%) 1 year, and 55 (33%) at 2 years. The proportion of patients with an improvement in 6–8 weeks ECS was higher on the CRT + Tras arm (46% vs. 38%), although not significantly different (<i>p</i> = .39). There was no correlation between pCR and ECS scores at 1 year, with 39% and 37% of pCR and non-pCR patients, respectively, having improved 1-year ECS scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The addition of trastuzumab to CRT for localized HER2+ EAC did not improve PROs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429825","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}