Olusegun I. Alatise MD, Israel A. Owoade MBBS, Oluwaleke J. Fayenuwo MPH, Nafisat O. O. Lawal MBBS, Cristina Olcese BS, Rivka Kahn MPH, Alexia Iasonos PhD, Adeoluwa O. Adeleye PhD, Christopher O. Bamidele MSc, Felicita Akinlusi BAgricTech, Temitope Ogunkoya MSc, Sola O. Olugbade MPH, Priscilla Akinsiku MSc, Opeyemi Akinlusi BSc, Abigael Akinwale BSc, Moyinoluwa Oyelakin BSc, Oluwadayomi Adedeji BSc, Gbenga S. Ogunleye MSc, Oluwabusayomi R. Ademakinwa PhD, Tajudeen Mohammed MBChB, Adewale Aderounmu MBBS, Funmilola Wuraola MD, Oluwatosin Z. Omoyiola MBChB, Omolade A. Betiku MBBS, Adeleye D. Omisore MSc, Olalekan Olasehinde MD, Dean Hosgood PhD, Adebola Adedimeji PhD, Anna Dare MD, Adewale O. Adisa MD, T. Peter Kingham MD
Background
Colorectal cancer (CRC) incidence is increasing in low- and middle-income countries, where late-stage presentation is common and survival rates remain poor. Early-detection programs are critical to improving outcomes.
Methods
A longitudinal early-detection study was conducted in Osun State, Nigeria. A 6-month community awareness campaign was implemented with posters, radio jingles, social media, and messaging disseminated via health and religious institutions. CRC knowledge was assessed before and after the intervention with the validated Bowel Cancer Awareness Measure questionnaire. Individuals with indicators of CRC were referred from peripheral facilities to an early-diagnosis (ED) clinic at a tertiary center. Demographic data, presenting features, and diagnostic outcomes were prospectively recorded. The primary end point was detection of advanced adenomas and CRC.
Results
Of 497 eligible participants, 322 (64.8%) completed pre- and postcampaign surveys. Awareness of CRC improved from 54 (16.8%) to 311 (96.9%) (p < .001). Good knowledge of CRC risk factors and symptoms also increased significantly (p < .001). A total of 329 individuals were navigated to the ED clinic; 168 (51.1%) were eligible for the protocol, and 116 (73.0%) completed colonoscopy. CRC was diagnosed in four patients (3.4%), with stage 0 (n = 2), II (n = 1), and III (n = 1). Advanced adenomas were identified in 11% of patients (13 of 116) who underwent colonoscopy.
Conclusions
Combining community engagement with patient navigation significantly increased CRC awareness and enabled the detection of advanced adenomas and early-stage cancers. Expanding this model to a national level is recommended to evaluate broader impact, cost-effectiveness, and potential implementation challenges.
{"title":"Customized early detection of colorectal cancer in Nigeria identifies advanced adenomas and early-stage disease","authors":"Olusegun I. Alatise MD, Israel A. Owoade MBBS, Oluwaleke J. Fayenuwo MPH, Nafisat O. O. Lawal MBBS, Cristina Olcese BS, Rivka Kahn MPH, Alexia Iasonos PhD, Adeoluwa O. Adeleye PhD, Christopher O. Bamidele MSc, Felicita Akinlusi BAgricTech, Temitope Ogunkoya MSc, Sola O. Olugbade MPH, Priscilla Akinsiku MSc, Opeyemi Akinlusi BSc, Abigael Akinwale BSc, Moyinoluwa Oyelakin BSc, Oluwadayomi Adedeji BSc, Gbenga S. Ogunleye MSc, Oluwabusayomi R. Ademakinwa PhD, Tajudeen Mohammed MBChB, Adewale Aderounmu MBBS, Funmilola Wuraola MD, Oluwatosin Z. Omoyiola MBChB, Omolade A. Betiku MBBS, Adeleye D. Omisore MSc, Olalekan Olasehinde MD, Dean Hosgood PhD, Adebola Adedimeji PhD, Anna Dare MD, Adewale O. Adisa MD, T. Peter Kingham MD","doi":"10.1002/cncr.70156","DOIUrl":"10.1002/cncr.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal cancer (CRC) incidence is increasing in low- and middle-income countries, where late-stage presentation is common and survival rates remain poor. Early-detection programs are critical to improving outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A longitudinal early-detection study was conducted in Osun State, Nigeria. A 6-month community awareness campaign was implemented with posters, radio jingles, social media, and messaging disseminated via health and religious institutions. CRC knowledge was assessed before and after the intervention with the validated Bowel Cancer Awareness Measure questionnaire. Individuals with indicators of CRC were referred from peripheral facilities to an early-diagnosis (ED) clinic at a tertiary center. Demographic data, presenting features, and diagnostic outcomes were prospectively recorded. The primary end point was detection of advanced adenomas and CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 497 eligible participants, 322 (64.8%) completed pre- and postcampaign surveys. Awareness of CRC improved from 54 (16.8%) to 311 (96.9%) (<i>p</i> < .001). Good knowledge of CRC risk factors and symptoms also increased significantly (<i>p</i> < .001). A total of 329 individuals were navigated to the ED clinic; 168 (51.1%) were eligible for the protocol, and 116 (73.0%) completed colonoscopy. CRC was diagnosed in four patients (3.4%), with stage 0 (<i>n</i> = 2), II (<i>n</i> = 1), and III (<i>n</i> = 1). Advanced adenomas were identified in 11% of patients (13 of 116) who underwent colonoscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Combining community engagement with patient navigation significantly increased CRC awareness and enabled the detection of advanced adenomas and early-stage cancers. Expanding this model to a national level is recommended to evaluate broader impact, cost-effectiveness, and potential implementation challenges.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802710","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}
Ok CY, Natu A, Daneshpajouhnejad P, et al. Chronic myelomonocytic leukemia in the young (aged 50 years and younger): Divergent clinical and molecular characteristics from the elderly. Cancer. 2025;e70176. doi:10.1002/cncr.70176
Please note that Daniel A. Arber’s middle initial was omitted in the originally published version of this article.
We apologize for this error.
Ok CY, Natu A, Daneshpajouhnejad P，等。慢性粒细胞白血病在年轻人（50岁及以下）：不同于老年人的临床和分子特征。癌症。2025;e70176。doi: 10.1002 / cncr。70176请注意，在这篇文章最初发表的版本中，省略了Daniel A. Arber中间的首字母。我们为这个错误道歉。
{"title":"Correction to “Chronic myelomonocytic leukemia in the young (aged 50 years and younger): Divergent clinical and molecular characteristics from the elderly”","authors":"","doi":"10.1002/cncr.70232","DOIUrl":"10.1002/cncr.70232","url":null,"abstract":"<p>Ok CY, Natu A, Daneshpajouhnejad P, et al. Chronic myelomonocytic leukemia in the young (aged 50 years and younger): Divergent clinical and molecular characteristics from the elderly. <i>Cancer</i>. 2025;e70176. doi:10.1002/cncr.70176</p><p>Please note that Daniel A. Arber’s middle initial was omitted in the originally published version of this article.</p><p>We apologize for this error.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792688","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}
Georges Gebrael MD, Neeraj Agarwal MD, Alicia K. Morgans MD, MPH, Randy Vince Jr MD, Umang Swami MD, MS, Angela Y. Jia MD, PhD, Nicholas Zaorsky MD, MS, Chadi Hage Chehade MD, Zeynep Irem Ozay MD, Shawn Malone MD, Scott C. Morgan MD, Msc, Christopher J. D. Wallis MD, PhD, Amar U. Kishan MD, Pedro C. Barata MD, MSc, Simon Chowdhury MD, PhD, Jorge A Garcia MD, Iris Sheng MD, Jason R. Brown MD, PhD, Eric J. Small MD, Yilun Sun PhD, Neal D. Shore MD, Fred Saad MD, Daniel E. Spratt MD, Soumyajit Roy MBBS, MSc
Background
Clinical studies have shown that outcomes of patients with prostate cancer could vary depending on race. In this study, the authors sought to determine if the treatment effect of apalutamide, an androgen receptor pathway inhibitor (ARPI), on overall survival (OS) varies depending on the race of the patient.
Methods
This pooled analysis includes individual patient data from two phase 3 trials, TITAN and SPARTAN, which randomized patients to androgen deprivation therapy (ADT) ± apalutamide in metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer, respectively. Race was self-identified and categorized as Asian, Black, White, and Others categories. The authors applied a stratified (stratification for the trial) multivariable Cox proportional hazards regression model to determine heterogeneity of treatment effect on OS after adjustment for age, performance status, body mass index, T- and N-stage, Gleason score, comorbidities, and exposure to statins and metformin.
Results
Overall, 2190 patients were included: 16.9% patients were Asian, 3.7% were Black, 67.4% were White, and 12.0% were from the Others category. The authors did not find any significant heterogeneity of treatment effect from apalutamide on OS across racial groups (interaction-p = .46). Among ADT plus apalutamide-treated patients, there was no association of race with OS (hazard ratio for Asian, 0.77 [95% CI, 0.56–1.06]; Black, 0.82 [95% CI, 0.49–1.37]; and Others, 1.00 [95% CI, 0.75–1.34], all compared to White).
Conclusions
In this study, the authors did not find any evidence of difference in the treatment effect of apalutamide on OS across patients of different races, although interpretation remains limited by poor representation of racial minorities. Among apalutamide-treated patients, there was no association of race with OS.
{"title":"Association of race and survival in patients treated with apalutamide: Pooled analysis of two phase 3 trials","authors":"Georges Gebrael MD, Neeraj Agarwal MD, Alicia K. Morgans MD, MPH, Randy Vince Jr MD, Umang Swami MD, MS, Angela Y. Jia MD, PhD, Nicholas Zaorsky MD, MS, Chadi Hage Chehade MD, Zeynep Irem Ozay MD, Shawn Malone MD, Scott C. Morgan MD, Msc, Christopher J. D. Wallis MD, PhD, Amar U. Kishan MD, Pedro C. Barata MD, MSc, Simon Chowdhury MD, PhD, Jorge A Garcia MD, Iris Sheng MD, Jason R. Brown MD, PhD, Eric J. Small MD, Yilun Sun PhD, Neal D. Shore MD, Fred Saad MD, Daniel E. Spratt MD, Soumyajit Roy MBBS, MSc","doi":"10.1002/cncr.70236","DOIUrl":"10.1002/cncr.70236","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Clinical studies have shown that outcomes of patients with prostate cancer could vary depending on race. In this study, the authors sought to determine if the treatment effect of apalutamide, an androgen receptor pathway inhibitor (ARPI), on overall survival (OS) varies depending on the race of the patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This pooled analysis includes individual patient data from two phase 3 trials, TITAN and SPARTAN, which randomized patients to androgen deprivation therapy (ADT) ± apalutamide in metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer, respectively. Race was self-identified and categorized as Asian, Black, White, and Others categories. The authors applied a stratified (stratification for the trial) multivariable Cox proportional hazards regression model to determine heterogeneity of treatment effect on OS after adjustment for age, performance status, body mass index, T- and N-stage, Gleason score, comorbidities, and exposure to statins and metformin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 2190 patients were included: 16.9% patients were Asian, 3.7% were Black, 67.4% were White, and 12.0% were from the Others category. The authors did not find any significant heterogeneity of treatment effect from apalutamide on OS across racial groups (interaction-<i>p</i> = .46). Among ADT plus apalutamide-treated patients, there was no association of race with OS (hazard ratio for Asian, 0.77 [95% CI, 0.56–1.06]; Black, 0.82 [95% CI, 0.49–1.37]; and Others, 1.00 [95% CI, 0.75–1.34], all compared to White).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this study, the authors did not find any evidence of difference in the treatment effect of apalutamide on OS across patients of different races, although interpretation remains limited by poor representation of racial minorities. Among apalutamide-treated patients, there was no association of race with OS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792657","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}
Charbel Chidiac MD, Paul Phan BS, Katherine M. McDermott MD, MHS, Christine A. Pratilas MD, Adam S. Levin MD, Christian F. Meyer MD, PhD, Nicolas J. Llosa MD, Alejandro V. Garcia MD, Mark B. Slidell MD, MPH, Daniel S. Rhee MD, MPH
Introduction
Sarcoma management is complex, requiring multidisciplinary care. Previous studies show improved outcomes at high-volume hospitals (HVHs), but optimal volume thresholds remain unclear. The aim was to identify hospital volume thresholds associated with improved survival for sarcoma patients across age groups.
Methods
Patients with Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, and nonrhabdomyosarcoma soft-tissue sarcoma were queried from the National Cancer Database (2004–2020). Patients were divided into children (0–17 years), young adults (YA) (18–39 years), and adults (≥40 years). The primary outcome was overall survival. Restricted cubic splines identified volume thresholds, which were validated using Kaplan–Meier curves and Cox regression.
Results
Among 71,463 patients, 7829 (10.9%) were children, 12,901 (18.1%) were YA, and 50,733 (71.0%) were adults. Identified HVH thresholds were 37 cases/year for all ages, five for children and YA, and 24 for adults. Using these thresholds, 17/1289 hospitals were HVHs for all ages, 30/413 for children, 40/970 for YA, and 19/1264 for adults. Treatment at HVHs was associated with better 5-year overall survival compared to low-volume hospitals for all ages (64.8% vs. 60.0%, p < .001) and adults (63.0% vs. 56.8%, p < .001). In multivariable analysis, HVH treatment was associated with better survival across all groups: all ages (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.83–0.88), children (aHR, 0.91; 95% CI, 0.83–0.98), YA (aHR, 0.94; 95% CI, 0.88–0.99), and adults (aHR, 0.81; 95% CI, 0.78–0.85).
Conclusion
Treatment at HVHs is associated with improved survival for sarcoma patients across all age groups. Our study defines distinct volume thresholds for children, young adults, and adults, guiding referrals and optimizing care.
肉瘤的治疗是复杂的，需要多学科的治疗。先前的研究表明，大容量医院（HVHs）的结果有所改善，但最佳容量阈值仍不清楚。目的是确定与各年龄组肉瘤患者生存率提高相关的医院容量阈值。方法从美国国家癌症数据库（2004-2020）中查询尤文氏肉瘤、骨肉瘤、横纹肌肉瘤和非横纹肌肉瘤软组织肉瘤患者。患者分为儿童（0 ~ 17岁）、青壮年（18 ~ 39岁）和成人（≥40岁）。主要终点是总生存期。限制三次样条确定了体积阈值，并使用Kaplan-Meier曲线和Cox回归进行了验证。结果71463例患者中，儿童7829例（10.9%），YA 12901例（18.1%），成人50733例（71.0%）。确定的HVH阈值为所有年龄段37例/年，儿童和青少年5例，成人24例。使用这些阈值，17/1289家医院为所有年龄段的hhs， 30/413家为儿童，40/970家为青少年，19/1264家为成人。与小容量医院相比，在HVHs治疗的所有年龄段（64.8% vs. 60.0%, p < 0.001）和成人（63.0% vs. 56.8%, p < 0.001）的5年总生存率更高。在多变量分析中，HVH治疗在所有组中均与更好的生存率相关：所有年龄组（校正风险比[aHR]， 0.85; 95% CI, 0.83-0.88）、儿童（aHR, 0.91; 95% CI, 0.83-0.98）、YA （aHR, 0.94; 95% CI, 0.88-0.99）和成人（aHR, 0.81; 95% CI, 0.78-0.85）。结论：在HVHs治疗可提高所有年龄组肉瘤患者的生存率。我们的研究为儿童、年轻人和成年人定义了不同的容量阈值，指导转诊和优化护理。
{"title":"Exploring hospital volume thresholds for improved sarcoma treatment across different age categories in the United States","authors":"Charbel Chidiac MD, Paul Phan BS, Katherine M. McDermott MD, MHS, Christine A. Pratilas MD, Adam S. Levin MD, Christian F. Meyer MD, PhD, Nicolas J. Llosa MD, Alejandro V. Garcia MD, Mark B. Slidell MD, MPH, Daniel S. Rhee MD, MPH","doi":"10.1002/cncr.70224","DOIUrl":"https://doi.org/10.1002/cncr.70224","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Sarcoma management is complex, requiring multidisciplinary care. Previous studies show improved outcomes at high-volume hospitals (HVHs), but optimal volume thresholds remain unclear. The aim was to identify hospital volume thresholds associated with improved survival for sarcoma patients across age groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, and nonrhabdomyosarcoma soft-tissue sarcoma were queried from the National Cancer Database (2004–2020). Patients were divided into children (0–17 years), young adults (YA) (18–39 years), and adults (≥40 years). The primary outcome was overall survival. Restricted cubic splines identified volume thresholds, which were validated using Kaplan–Meier curves and Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 71,463 patients, 7829 (10.9%) were children, 12,901 (18.1%) were YA, and 50,733 (71.0%) were adults. Identified HVH thresholds were 37 cases/year for all ages, five for children and YA, and 24 for adults. Using these thresholds, 17/1289 hospitals were HVHs for all ages, 30/413 for children, 40/970 for YA, and 19/1264 for adults. Treatment at HVHs was associated with better 5-year overall survival compared to low-volume hospitals for all ages (64.8% vs. 60.0%, <i>p</i> < .001) and adults (63.0% vs. 56.8%, <i>p</i> < .001). In multivariable analysis, HVH treatment was associated with better survival across all groups: all ages (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.83–0.88), children (aHR, 0.91; 95% CI, 0.83–0.98), YA (aHR, 0.94; 95% CI, 0.88–0.99), and adults (aHR, 0.81; 95% CI, 0.78–0.85).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Treatment at HVHs is associated with improved survival for sarcoma patients across all age groups. Our study defines distinct volume thresholds for children, young adults, and adults, guiding referrals and optimizing care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792507","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}
Irfan Yasin MD, Anna Stengel MSc, Haipeng Shao MD, PhD, Amandeep Kaur MD, Emily F. Mason MD, PhD, Pranav P. Patwardhan MD, Nathanael G. Bailey MD, Sharmila Ghosh MD, Kedar V. Inamdar MD, PhD, Anand A. Patel MD, Madhavi Pandiri MD, Jingjing Zhang MD, PhD, Payal Sojitra MD, Hamza Tariq MD, Zenggang Pan MD, PhD, Danica Wiredja MD, PhD, Peng Wang MD, Melissa Y. Tjota MD, PhD, Jeremy P. Segal MD, Hong Chang MD, PhD, David A. Sallman MD, Daniel A. Arber MD, Ayalew Tefferi MD, Talha Badar MD, Anamarija M. Perry MD, Claudia Haferlach MD, Angela M. Lager PhD, Girish Venkataraman MD
Background
Isolated chromosome 5/5q losses (–5/5q) without TP53 mutations are associated with favorable outcomes in myeloid neoplasms (MN) with <5% blasts. However, the clinical implication of concurrent −5/5q and TP53 aberrations in MN with ≥5% blasts is poorly understood.
Methods
Patients with TP53-mutated MN carrying ≥5% blasts assessing the prognostic impact of -5/5q on 24-month overall survival (OS24) were examined.
Results
Of 587 patients, 515 (88%) exhibited −5/5q overwhelmingly in the context of a complex karyotype (98.3% vs. 61.1% complex karyotype without −5/5q; p < .0001) and multihit TP53 allelic state (88.3% vs. 56.9%; p < .0001). Proportions of patients with blasts ≥20% were comparable between groups with and without −5/5q; p = 0.26. Notably, patients with −5/5q exhibited significantly fewer coalterations; p < .0001. Looking at outcomes, presence of −5/5q was associated with shorter median 24-month overall survival (7.8 months vs. 11.2 months; pLog-rank = .012), an effect restricted to subgroups with blasts <20% (p = .039; N = 163), absent −7/7q (p = .007; N = 225), or WHO5-defined single hit allelic state (p = 0.030; N = 91). Importantly, −5/5q retained independent adverse prognostic significance regardless of TP53 allelic state in a multivariable model. Furthermore, among the subset of 75 (13%) patients undergoing allogeneic stem cell transplantation, −5/5q predicted significantly shorter median 5-year posttransplant survival (16.2 months vs. median not reached; pLog-rank = .009).
Conclusions
These findings emphasize the independent prognostic relevance of chromosome 5/5q losses underscoring the clinical relevance of cytogenetic testing for −5/5q even in this high-risk cohort.
无TP53突变的分离染色体5/5q缺失（-5/5q）与具有<；5%原细胞的髓系肿瘤（MN）的良好预后相关。然而，在≥5%的MN细胞中并发−5/5q和TP53畸变的临床意义尚不清楚。方法检测携带≥5%原细胞的tp53突变MN患者，评估-5/5q对24个月总生存（OS24）的预后影响。结果587例患者中，515例（88%）在复杂核型（98.3% vs. 61.1%没有- 5/5q的复杂核型）和多重TP53等位基因状态（88.3% vs. 56.9%; p < .0001）中绝大多数表现为- 5/5q。有- 5/5q和没有- 5/5q的两组间，原细胞≥20%的患者比例具有可比性；P = 0.26。值得注意的是，−5/5q患者的共变明显减少；P < .0001；观察结果，−5/5q的存在与较短的中位24个月总生存期相关（7.8个月vs 11.2个月；pLog-rank = 0.012），这种影响仅限于胚素<；20% （p = 0.039; N = 163）、缺失−7/7q （p = 0.0007; N = 225）或who5定义的单命中等位基因状态（p = 0.030; N = 91）的亚组。重要的是，在多变量模型中，无论TP53等位基因状态如何，−5/5q仍然具有独立的不良预后意义。此外，在接受同种异体干细胞移植的75例（13%）患者中，−5/5q预测移植后5年平均生存期显著缩短（16.2个月vs.中位未达到；pLog-rank = 0.009）。这些发现强调了5/5q染色体缺失与预后的独立相关性，强调了- 5/5q细胞遗传学检测的临床相关性，即使在这一高危队列中也是如此。
{"title":"Characterization of chromosome 5 aberrations in TP53 mutated myeloid neoplasms with ≥5% blasts: An International TP53 Investigators Network (iTiN) study","authors":"Irfan Yasin MD, Anna Stengel MSc, Haipeng Shao MD, PhD, Amandeep Kaur MD, Emily F. Mason MD, PhD, Pranav P. Patwardhan MD, Nathanael G. Bailey MD, Sharmila Ghosh MD, Kedar V. Inamdar MD, PhD, Anand A. Patel MD, Madhavi Pandiri MD, Jingjing Zhang MD, PhD, Payal Sojitra MD, Hamza Tariq MD, Zenggang Pan MD, PhD, Danica Wiredja MD, PhD, Peng Wang MD, Melissa Y. Tjota MD, PhD, Jeremy P. Segal MD, Hong Chang MD, PhD, David A. Sallman MD, Daniel A. Arber MD, Ayalew Tefferi MD, Talha Badar MD, Anamarija M. Perry MD, Claudia Haferlach MD, Angela M. Lager PhD, Girish Venkataraman MD","doi":"10.1002/cncr.70210","DOIUrl":"https://doi.org/10.1002/cncr.70210","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Isolated chromosome 5/5q losses (–5/5q) without <i>TP53</i> mutations are associated with favorable outcomes in myeloid neoplasms (MN) with <5% blasts. However, the clinical implication of concurrent −5/5q and <i>TP53</i> aberrations in MN with ≥5% blasts is poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with <i>TP53</i>-mutated MN carrying ≥5% blasts assessing the prognostic impact of -5/5q on 24-month overall survival (OS24) were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 587 patients, 515 (88%) exhibited −5/5q overwhelmingly in the context of a complex karyotype (98.3% vs. 61.1% complex karyotype without −5/5q; <i>p <</i> .0001) and multihit <i>TP53</i> allelic state (88.3% vs. 56.9%; <i>p <</i> .0001). Proportions of patients with blasts ≥20% were comparable between groups with and without −5/5q; <i>p =</i> 0.26. Notably, patients with −5/5q exhibited significantly fewer coalterations; <i>p <</i> .0001. Looking at outcomes, presence of −5/5q was associated with shorter median 24-month overall survival (7.8 months vs. 11.2 months; <i>p</i><sub><i>Log-rank</i></sub> = .012), an effect restricted to subgroups with blasts <20% (<i>p =</i> .039; <i>N =</i> 163), absent −7/7q (<i>p =</i> .007; <i>N =</i> 225), or WHO5-defined single hit allelic state (<i>p =</i> 0.030; <i>N =</i> 91). Importantly, −5/5q retained independent adverse prognostic significance regardless of <i>TP53</i> allelic state in a multivariable model. Furthermore, among the subset of 75 (13%) patients undergoing allogeneic stem cell transplantation, −5/5q predicted significantly shorter median 5-year posttransplant survival (16.2 months vs. median not reached; <i>p</i><sub><i>Log-rank</i></sub> = .009).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings emphasize the independent prognostic relevance of chromosome 5/5q losses underscoring the clinical relevance of cytogenetic testing for −5/5q even in this high-risk cohort.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792441","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}
Fen Saj MD, DM, Felicity K. Namayanja MBChB, MPH, Lianchun Xiao MS, Mitesh J Borad MD, Robin Kate Kelley MD, Lipika Goyal MD, MPhil, Nilofer S. Azad MD, Melinda Bachini, Stacie Lindsey BA, Shubham Pant MD, Juan W. Valle MBChB, MSc, FRCP, Lola A Fashoyin-Aje MD, MPH, Milind Javle MD
Background
Eligibility criteria for clinical trials are crucial for maintaining safety and study integrity. However, overly restrictive criteria can result in unrepresentative trial populations, leading to gaps in understanding real-world treatment efficacy. Addressing potentially modifiable exclusions (PMEs) could enhance trial accessibility and participation without compromising safety.
Methods
The authors retrospectively analyzed screen-failed patients with biliary tract cancer or pancreatic cancer between August 2019 and November 2024 at The University of Texas MD Anderson Cancer Center. Screen-failed patients were those who provided informed consent but did not participate for any reason. Clinical data were obtained from screening logs and electronic health records. PMEs were identified and validated by two independent medical oncologists.
Results
Of 585 screen-failed patients from 18 trials, 509 were analyzed (367 with pancreatic cancer and 142 with biliary tract cancer) after excluding 76 because of incomplete data. Leading causes of screen failure were declined participation (19%), comorbidities (12%), suboptimal organ function (11%), absence of a biomarker (10%), and insufficient biospecimens (7%). Reasons for declining included preference for standard care (23%), travel (22%), and competing trials (5%). The authors identified 69 patients (13.6%) who had PMEs (primarily borderline laboratory abnormalities), including liver function (23%), kidney function (20%), platelet count (12%), hemoglobin (7%), and white blood cell count (6%) abnormalities. Other PMEs included previous or concurrent malignancies (9%) and viral hepatitis (4%). PMEs were evenly distributed across trials.
Conclusions
Rigid eligibility criteria exclude stable patients who might benefit from investigational treatments. Easing criteria related to incidental or asymptomatic laboratory abnormalities could broaden trial accessibility and improve enrollment in populations that are more representative of real-world use.
{"title":"Broadening the gates: Analysis of potentially modifiable study entry criteria in pancreatic and biliary tract cancer trials","authors":"Fen Saj MD, DM, Felicity K. Namayanja MBChB, MPH, Lianchun Xiao MS, Mitesh J Borad MD, Robin Kate Kelley MD, Lipika Goyal MD, MPhil, Nilofer S. Azad MD, Melinda Bachini, Stacie Lindsey BA, Shubham Pant MD, Juan W. Valle MBChB, MSc, FRCP, Lola A Fashoyin-Aje MD, MPH, Milind Javle MD","doi":"10.1002/cncr.70227","DOIUrl":"https://doi.org/10.1002/cncr.70227","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Eligibility criteria for clinical trials are crucial for maintaining safety and study integrity. However, overly restrictive criteria can result in unrepresentative trial populations, leading to gaps in understanding real-world treatment efficacy. Addressing potentially modifiable exclusions (PMEs) could enhance trial accessibility and participation without compromising safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors retrospectively analyzed <i>screen-failed</i> patients with biliary tract cancer or pancreatic cancer between August 2019 and November 2024 at The University of Texas MD Anderson Cancer Center. Screen-failed patients were those who provided informed consent but did not participate for any reason. Clinical data were obtained from screening logs and electronic health records. PMEs were identified and validated by two independent medical oncologists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 585 screen-failed patients from 18 trials, 509 were analyzed (367 with pancreatic cancer and 142 with biliary tract cancer) after excluding 76 because of incomplete data. Leading causes of screen failure were declined participation (19%), comorbidities (12%), suboptimal organ function (11%), absence of a biomarker (10%), and insufficient biospecimens (7%). Reasons for declining included preference for standard care (23%), travel (22%), and competing trials (5%). The authors identified 69 patients (13.6%) who had PMEs (primarily borderline laboratory abnormalities), including liver function (23%), kidney function (20%), platelet count (12%), hemoglobin (7%), and white blood cell count (6%) abnormalities. Other PMEs included previous or concurrent malignancies (9%) and viral hepatitis (4%). PMEs were evenly distributed across trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Rigid eligibility criteria exclude stable patients who might benefit from investigational treatments. Easing criteria related to incidental or asymptomatic laboratory abnormalities could broaden trial accessibility and improve enrollment in populations that are more representative of real-world use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792526","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}
Elisabeth T. Tracy MD, Harold J. Leraas MD, Michael R. Phillips MD, MSCR, Kyle J. Van Arendonk MD, PhD, Katherine T. Flynn-O’Brien MD, Benjamin E. Padilla MD, Katie W. Russell MD, Vanessa Niba MD, Samir K. Gadepalli MD, Adam B. Goldin MD, MPH, Matthew Hall PhD, Peter F. Ehrlich MD, MSc
Background
The complexity of pediatric solid tumor care has been associated with improved outcomes but has also increased the burden of care for families. This study aimed to understand and quantify the medicalized days experienced by children with solid tumors during the first year after diagnosis, and changes over time, via national population-level data.
Methods
A retrospective population-based cohort study was performed of children enrolled in a national claims database that tracks health care utilization across medical encounters. Children (aged <18 years) with a solid tumor diagnosis were identified. The number of medicalized days over the first year after diagnosis was quantified. We also compared trends over time.
Results
For 5263 children with solid tumors, the median number of medicalized days during the first year after diagnosis was 45 days per child (interquartile range [IQR], 45.0–45.3 days). Children saw a median of three providers (IQR, two to seven providers), and underwent a median of 3.8 surgical procedures (IQR, 3.8–3.9 surgical procedures). Total medicalized days increased significantly across the study period (p < .001). Lost economic productivity for families ranged from 14.4% to 22.3% of household income.
Conclusions
Children with solid tumors experience a high number of medicalized days in the first year after diagnosis. Furthermore, the number of medicalized days has increased over the last decade. Quantifying medicalized days provides a way to track the social and economic burdens of care. Better understanding of this care burden may provide an opportunity for physicians, patient advocates, and policymakers to address the financial toxicity of treatment.
{"title":"Characterizing the burden of care for children with solid tumors in the United States: A cross-sectional analysis from the Child Health Evaluation of Surgical Services Group","authors":"Elisabeth T. Tracy MD, Harold J. Leraas MD, Michael R. Phillips MD, MSCR, Kyle J. Van Arendonk MD, PhD, Katherine T. Flynn-O’Brien MD, Benjamin E. Padilla MD, Katie W. Russell MD, Vanessa Niba MD, Samir K. Gadepalli MD, Adam B. Goldin MD, MPH, Matthew Hall PhD, Peter F. Ehrlich MD, MSc","doi":"10.1002/cncr.70193","DOIUrl":"10.1002/cncr.70193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The complexity of pediatric solid tumor care has been associated with improved outcomes but has also increased the burden of care for families. This study aimed to understand and quantify the medicalized days experienced by children with solid tumors during the first year after diagnosis, and changes over time, via national population-level data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective population-based cohort study was performed of children enrolled in a national claims database that tracks health care utilization across medical encounters. Children (aged <18 years) with a solid tumor diagnosis were identified. The number of medicalized days over the first year after diagnosis was quantified. We also compared trends over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For 5263 children with solid tumors, the median number of medicalized days during the first year after diagnosis was 45 days per child (interquartile range [IQR], 45.0–45.3 days). Children saw a median of three providers (IQR, two to seven providers), and underwent a median of 3.8 surgical procedures (IQR, 3.8–3.9 surgical procedures). Total medicalized days increased significantly across the study period (<i>p</i> < .001). Lost economic productivity for families ranged from 14.4% to 22.3% of household income.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Children with solid tumors experience a high number of medicalized days in the first year after diagnosis. Furthermore, the number of medicalized days has increased over the last decade. Quantifying medicalized days provides a way to track the social and economic burdens of care. Better understanding of this care burden may provide an opportunity for physicians, patient advocates, and policymakers to address the financial toxicity of treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779759","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}
Karen Llave PhD, Jiwon Kim PhD, Maja Kuharic PhD, Kathryn Jackson MS, Nicola Lancki MPH, Kimberly A. Webster MA, David Cella PhD
Background
Patient-reported outcomes are valuable sources of information in research and clinical care, particularly in populations experiencing long-term effects on health-related quality of life such as patients with cancer. Identifying meaningful differences and changes in patient-reported outcomes can prove useful in research and clinical settings.
Methods
Data from a system-wide symptom-management intervention trial were analyzed. Patients with cancer completed Patient-Reported Outcomes Measurement Information System (PROMIS) computer-adaptive tests in pain, fatigue, depression, anxiety, and physical function at baseline and 6 months. The authors used a combination of distribution-based and anchor-based approaches to estimate meaningful differences in PROMIS scores at baseline. Meaningful change estimates were calculated using mean changes in PROMIS scores in response to selected anchors.
Results
The sample (n = 3907) was predominantly female (66.1%) and non-Hispanic (84.2%). Overall, the sample reported PROMIS scores close to the general population standard (mean ± standard deviation score, 50 ± 10). Longitudinal anchor-based estimates ranged from 2.4 to 8.0 points for pain interference, 2.0–4.4 points for depression, 2.2–4.5 points for anxiety, 2.0–6.3 points for fatigue, and 1.9–4.4 points for physical functioning. Longitudinal, anchor-based findings revealed smaller changes than cross-sectional differences indicating the responsiveness of PROMIS measures to patient-reported meaningful changes over time. Supporting distribution-based information using SEM criteria produced generally smaller values, ranging from 1.14 for depression to 2.14 for fatigue.
Conclusions
PROMIS computer-adaptive test measures of pain, fatigue, anxiety, depression, and physical function are sensitive to group differences and changes over time. Regular symptom monitoring in conjunction with the recommended thresholds could be useful in research and clinical settings.
{"title":"Meaningful differences and changes for five Patient-Reported Outcomes Measurement Information System domains in a large cohort of patients with cancer","authors":"Karen Llave PhD, Jiwon Kim PhD, Maja Kuharic PhD, Kathryn Jackson MS, Nicola Lancki MPH, Kimberly A. Webster MA, David Cella PhD","doi":"10.1002/cncr.70219","DOIUrl":"10.1002/cncr.70219","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patient-reported outcomes are valuable sources of information in research and clinical care, particularly in populations experiencing long-term effects on health-related quality of life such as patients with cancer. Identifying meaningful differences and changes in patient-reported outcomes can prove useful in research and clinical settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from a system-wide symptom-management intervention trial were analyzed. Patients with cancer completed Patient-Reported Outcomes Measurement Information System (PROMIS) computer-adaptive tests in pain, fatigue, depression, anxiety, and physical function at baseline and 6 months. The authors used a combination of distribution-based and anchor-based approaches to estimate meaningful differences in PROMIS scores at baseline. Meaningful change estimates were calculated using mean changes in PROMIS scores in response to selected anchors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The sample (<i>n</i> = 3907) was predominantly female (66.1%) and non-Hispanic (84.2%). Overall, the sample reported PROMIS scores close to the general population standard (mean ± standard deviation score, 50 ± 10). Longitudinal anchor-based estimates ranged from 2.4 to 8.0 points for pain interference, 2.0–4.4 points for depression, 2.2–4.5 points for anxiety, 2.0–6.3 points for fatigue, and 1.9–4.4 points for physical functioning. Longitudinal, anchor-based findings revealed smaller changes than cross-sectional differences indicating the responsiveness of PROMIS measures to patient-reported meaningful changes over time. Supporting distribution-based information using SEM criteria produced generally smaller values, ranging from 1.14 for depression to 2.14 for fatigue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PROMIS computer-adaptive test measures of pain, fatigue, anxiety, depression, and physical function are sensitive to group differences and changes over time. Regular symptom monitoring in conjunction with the recommended thresholds could be useful in research and clinical settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779800","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}
The US Food and Drug Administration (FDA) has granted accelerated approval to the oral, irreversible, HER2-selective tyrosine kinase inhibitor zongertinib for adults with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) with HER2-activating mutations.1
“Zongertinib is the first oral, targeted therapy approved for patients with HER2-mutated NSCLC,” says Shetal Patel, MD, PhD, an assistant professor of medicine at the University of North Carolina School of Medicine in Chapel Hill.
Approximately 2%–4% of NSCLC tumors have an activating mutation in HER2.2 The only other FDA-approved therapy targeting HER2 in NSCLC is the antibody–drug conjugate trastuzumab deruxtecan, which is administered intravenously.3
Zongertinib was approved based on results from cohort 1 of the phase 1a/1b Beamion LUNG-1 trial.4 Cohort 1 included 75 patients with NSCLC harboring a mutation in the HER2 tyrosine kinase domain who had received prior platinum-based chemotherapy. Patients received zongertinib at a dose of 120 mg.
The primary endpoint of an objective response assessed by blinded independent central review was achieved in 71% of the patients in cohort 1, with confirmed complete responses in 7% and partial responses in 64%.
Responses to zongertinib were durable with a median duration of response of 14.1 months and a median progression-free survival of 12.4 months.
Twenty-eight patients had brain metastases at screening. A confirmed systemic objective response was seen in 64% of these patients; this, the researchers wrote, “suggests that zongertinib may be a promising treatment option in patients with brain metastases.”
“Notably, the toxicity profile of zongertinib was quite manageable,” Dr Patel says, “with mostly grade 1 and 2 diarrhea and rash seen.”
Grade 3 or higher drug-related adverse events occurred in 17% of the patients. No cases of interstitial lung disease were reported.
According to Dr Patel, clinicians should keep in mind that zongertinib was approved for patients with unresectable or metastatic NSCLC and HER2 tyrosine kinase domain mutations who have received prior systemic therapy.
“Additional cohorts of the Beamion LUNG-1 study evaluated the activity of zongertinib in previously untreated patients,” she says. “It is also important to remember that the recommended dose for zongertinib is based on body weight.”
Specifically, the FDA approval noted that patients weighing less than 90 kg should receive 120 mg once daily; patients weighing 90 kg or more should receive 180 mg once daily.1
{"title":"Oral TKI zongertinib gains accelerated approval for HER2-mutant NSCLC","authors":"Leah Lawrence","doi":"10.1002/cncr.70145","DOIUrl":"10.1002/cncr.70145","url":null,"abstract":"<p>The US Food and Drug Administration (FDA) has granted accelerated approval to the oral, irreversible, HER2-selective tyrosine kinase inhibitor zongertinib for adults with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) with <i>HER2</i>-activating mutations.<span><sup>1</sup></span></p><p>“Zongertinib is the first oral, targeted therapy approved for patients with <i>HER2</i>-mutated NSCLC,” says Shetal Patel, MD, PhD, an assistant professor of medicine at the University of North Carolina School of Medicine in Chapel Hill.</p><p>Approximately 2%–4% of NSCLC tumors have an activating mutation in <i>HER2</i>.<span><sup>2</sup></span> The only other FDA-approved therapy targeting <i>HER2</i> in NSCLC is the antibody–drug conjugate trastuzumab deruxtecan, which is administered intravenously.<span><sup>3</sup></span></p><p>Zongertinib was approved based on results from cohort 1 of the phase 1a/1b Beamion LUNG-1 trial.<span><sup>4</sup></span> Cohort 1 included 75 patients with NSCLC harboring a mutation in the <i>HER2</i> tyrosine kinase domain who had received prior platinum-based chemotherapy. Patients received zongertinib at a dose of 120 mg.</p><p>The primary endpoint of an objective response assessed by blinded independent central review was achieved in 71% of the patients in cohort 1, with confirmed complete responses in 7% and partial responses in 64%.</p><p>Responses to zongertinib were durable with a median duration of response of 14.1 months and a median progression-free survival of 12.4 months.</p><p>Twenty-eight patients had brain metastases at screening. A confirmed systemic objective response was seen in 64% of these patients; this, the researchers wrote, “suggests that zongertinib may be a promising treatment option in patients with brain metastases.”</p><p>“Notably, the toxicity profile of zongertinib was quite manageable,” Dr Patel says, “with mostly grade 1 and 2 diarrhea and rash seen.”</p><p>Grade 3 or higher drug-related adverse events occurred in 17% of the patients. No cases of interstitial lung disease were reported.</p><p>According to Dr Patel, clinicians should keep in mind that zongertinib was approved for patients with unresectable or metastatic NSCLC and <i>HER2</i> tyrosine kinase domain mutations who have received prior systemic therapy.</p><p>“Additional cohorts of the Beamion LUNG-1 study evaluated the activity of zongertinib in previously untreated patients,” she says. “It is also important to remember that the recommended dose for zongertinib is based on body weight.”</p><p>Specifically, the FDA approval noted that patients weighing less than 90 kg should receive 120 mg once daily; patients weighing 90 kg or more should receive 180 mg once daily.<span><sup>1</sup></span></p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766648","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}
Zhong Fan MD, Qi-Wen Chen MMed, Xiu-Ya Huang MMed, Qiang Fu MMed, Hui-Rong Mai MD, Xing-Jiang Long MD, Qiao-Ru Li MMed, Li-Li Liu MMed, Ri-Yang Liu MB, Fei He MMed, Bi-Yun Guo MMed, Min-Hui Zeng MMed, Wu-Qing Wan MD, Wei-Na Zhang MD, Hai-Xia Guo MD, Dun-Hua Zhou MD, Ya-Wei Zou MD, Wen-Jie Xiong MMed, Xiao-Bo Zhou MB, Hui-Qin Chen MD, Li-Min Lin MB, Hao-Yan Ren MB, Xin Tian MD, Hong-Ying Wei MD, He-Kui Lan MMed, Jiao Jin MB, Cong Liang MD, Xue-Qun Luo MMed, Li-Bin Huang MD, Li-Hua Yang MD, Xiao-Li Zhang MMed
Background
Chronic myeloid leukemia (CML) is rare in children and often shows more aggressive features than in adults. Real-world data on the efficacy and safety of frontline nilotinib in pediatric CML in chronic phase (CML-CP) remain limited.
Methods
This prospective multicenter real-world study evaluated the efficacy, safety, and pharmacokinetics of frontline nilotinib in newly diagnosed pediatric CML-CP across 26 hospitals in China between January 2023 and April 2025. Patients received nilotinib 230 mg/m2 twice daily. Primary end points were complete cytogenetic response (CCyR) at six cycles and major molecular response (MMR) at 12 cycles. Secondary end points included time to MMR, event-free survival (EFS), and safety.
Results
Among 59 enrolled patients (median age, 10.6 years), 71.8% (28/39) achieved MMR at 12 cycles and all achieved CCyR at six cycles. Median time to MMR was 6.2 (3.3, 12.2) months, and 2-year EFS was 93.3% (84.4%–100%). Nilotinib trough concentrations (Ctrough) correlated negatively with BCR::ABL1 transcript levels at cycles 6 and 12. Patients with Ctrough >950 ng/mL were three to five times more likely to reach MMR, whereas those with Ctrough ≥1500 ng/mL had a 6.5-fold higher risk of hyperbilirubinemia.
Conclusions
Frontline nilotinib thus shows strong efficacy and manageable safety in pediatric CML-CP. Higher drug exposure predicts deeper molecular responses but increases toxicity, supporting the potential role of therapeutic drug monitoring.
{"title":"Real-world efficacy and adverse events of frontline nilotinib in pediatric chronic myeloid leukemia in chronic phase: A prospective multicenter study from SCCCG[PLUS]-CML 2023","authors":"Zhong Fan MD, Qi-Wen Chen MMed, Xiu-Ya Huang MMed, Qiang Fu MMed, Hui-Rong Mai MD, Xing-Jiang Long MD, Qiao-Ru Li MMed, Li-Li Liu MMed, Ri-Yang Liu MB, Fei He MMed, Bi-Yun Guo MMed, Min-Hui Zeng MMed, Wu-Qing Wan MD, Wei-Na Zhang MD, Hai-Xia Guo MD, Dun-Hua Zhou MD, Ya-Wei Zou MD, Wen-Jie Xiong MMed, Xiao-Bo Zhou MB, Hui-Qin Chen MD, Li-Min Lin MB, Hao-Yan Ren MB, Xin Tian MD, Hong-Ying Wei MD, He-Kui Lan MMed, Jiao Jin MB, Cong Liang MD, Xue-Qun Luo MMed, Li-Bin Huang MD, Li-Hua Yang MD, Xiao-Li Zhang MMed","doi":"10.1002/cncr.70225","DOIUrl":"10.1002/cncr.70225","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic myeloid leukemia (CML) is rare in children and often shows more aggressive features than in adults. Real-world data on the efficacy and safety of frontline nilotinib in pediatric CML in chronic phase (CML-CP) remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective multicenter real-world study evaluated the efficacy, safety, and pharmacokinetics of frontline nilotinib in newly diagnosed pediatric CML-CP across 26 hospitals in China between January 2023 and April 2025. Patients received nilotinib 230 mg/m<sup>2</sup> twice daily. Primary end points were complete cytogenetic response (CCyR) at six cycles and major molecular response (MMR) at 12 cycles. Secondary end points included time to MMR, event-free survival (EFS), and safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 59 enrolled patients (median age, 10.6 years), 71.8% (28/39) achieved MMR at 12 cycles and all achieved CCyR at six cycles. Median time to MMR was 6.2 (3.3, 12.2) months, and 2-year EFS was 93.3% (84.4%–100%). Nilotinib trough concentrations (Ctrough) correlated negatively with <i>BCR::ABL1</i> transcript levels at cycles 6 and 12. Patients with Ctrough >950 ng/mL were three to five times more likely to reach MMR, whereas those with Ctrough ≥1500 ng/mL had a 6.5-fold higher risk of hyperbilirubinemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Frontline nilotinib thus shows strong efficacy and manageable safety in pediatric CML-CP. Higher drug exposure predicts deeper molecular responses but increases toxicity, supporting the potential role of therapeutic drug monitoring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766690","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}
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