Journal of Clinical Oncology最新文献

{"title":"Reply to: Adjuvant Treatment Options and Modalities in Pancreatic Adenocarcinoma: Insights From ESPAC4.","authors":"Daniel H Palmer, Richard J Jackson, Christoph Springfeld, Thilo Hackert, Christoph W Michalski, John P Neoptolemos","doi":"10.1200/JCO-25-00333","DOIUrl":"10.1200/JCO-25-00333","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2229-2230"},"PeriodicalIF":42.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752959","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":"Development and Validation of a Novel Prediction Model for Hearing Loss From Cisplatin Chemotherapy.","authors":"Joshua Millstein, Shahrad R Rassekh, Austin L Brown, Qi Nie, Adam J Esbenshade, Kristin R Knight, Michael E Scheurer, Lillian Sung, Beth Brooks, Diana J Moke, Colin J D Ross, Michael Wright, Victoria Mena, Teresa Rushing, Bruce C Carleton, Etan Orgel","doi":"10.1200/JCO-24-01861","DOIUrl":"10.1200/JCO-24-01861","url":null,"abstract":"<p><strong>Purpose: </strong>Cisplatin treats many common tumors but causes permanent and debilitating hearing loss (HL). The objective of this study was to develop and externally validate a predictive model of HL in cisplatin-treated children and adolescent cancer survivors.</p><p><strong>Methods: </strong>The Pediatric Holistic Evaluation of Auditory Risk (PedsHEAR) model architecture used several machine learning approaches followed by an ensemble predictor. The primary end point was post-treatment communication-affecting HL (International Society of Pediatric Oncology Ototoxicity Scale [SIOP] Grade ≥2). PedsHEAR was developed from a multicenter data set of cisplatin-exposed patients up to 21 years old (1984-2017) and externally validated using data from the Children's Oncology Group ACCL05C1 study (2007-2012) and two combined institutional cohorts (1988-2022). The model predicts post-treatment HL in each patient (probability [%], 95% CI) and classifies patients as low, intermediate, or high risk for HL (probability HL <0.33, 0.33-0.60, >0.60, respectively).</p><p><strong>Results: </strong>In the training data set (n = 1,115, median age 6.3 years, SIOP Grade ≥2 HL 44%), PedsHEAR demonstrated excellent discrimination (AUC, 0.93 [95% CI, 0.92 to 0.95]) and then successfully validated within the internal (testing; AUC, 0.79 [95% CI, 0.74 to 0.85]) and two external validation cohorts (AUC, 0.74 and AUC, 0.67). In an aggregate validation cohort (n = 631), the model predicted the probability of HL (AUC, 0.76 [95% CI, 0.72 to 0.79]) and classified 22% (141/631), 71% (447/631), and 7% (43/631) of patients as low, intermediate, or high risk for HL.</p><p><strong>Conclusion: </strong>PedsHEAR predicted SIOP Grade ≥2 HL in pediatric cisplatin-treated patients. This is the first validated model to successfully predict cisplatin-induced HL in a broadly representative population treated with diverse regimens across a range of treatment settings.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2173-2183"},"PeriodicalIF":42.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994523","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":"Overall Survival and the Evolving Benefit-Risk Assessment for Poly (ADP-ribose) Polymerase Inhibitors in Advanced Ovarian Cancer.","authors":"Mirat Shah, Ting-Yu Chen, Gwynn Ison, Mallorie H Fiero, Hui Zhang, Xin Gao, Marc Neilson, Kirsten B Goldberg, Abhilasha Nair, Tiffany K Ricks, William F Pierce, Nicole Gormley, Marc R Theoret, Shenghui Tang, Richard Pazdur, Paul G Kluetz, Laleh Amiri-Kordestani","doi":"10.1200/JCO-24-02834","DOIUrl":"10.1200/JCO-24-02834","url":null,"abstract":"<p><p>From 2014 through 2019, the US Food and Drug Administration (FDA) granted approval to six indications for poly (ADP-ribose) polymerase (PARP) inhibitors in advanced epithelial ovarian cancer (EOC). From 2022 through 2023, these six indications were withdrawn or narrowed after observation of a potential detrimental effect on overall survival (OS) in four randomized controlled trials. The indications for niraparib, olaparib, and rucaparib for the treatment of <i>BRCA</i>-mutated or homologous recombination deficiency-positive advanced EOC were withdrawn. The indications for niraparib, olaparib, and rucaparib for the maintenance treatment of recurrent EOC were narrowed to only patients with <i>BRCA</i> mutations. Recognizing the clinical implications of these regulatory actions, herein we describe the FDA's decision-making process and the rationale behind the removal or narrowing of these indications for PARP inhibitors in advanced EOC. Furthermore, this article provides insight into the FDA's interpretation of potential OS detriments and subgroup analyses to shape regulatory decisions.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2218-2227"},"PeriodicalIF":42.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101839","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":"Randomized Phase III Trial of Ramucirumab Beyond Progression Plus Irinotecan in Patients With Ramucirumab-Refractory Advanced Gastric Cancer: RINDBeRG Trial.","authors":"Daisuke Sakai, Shigenori Kadowaki, Ryohei Kawabata, Hiroki Hara, Hironaga Satake, Masazumi Takahashi, Atsushi Takeno, Hiroo Imai, Keiko Minashi, Takeshi Kawakami, Shogen Boku, Jin Matsuyama, Yasuhiro Sakamoto, Kentaro Sawada, Masato Kataoka, Hisato Kawakami, Toshio Shimokawa, Narikazu Boku, Taroh Satoh","doi":"10.1200/JCO.24.01119","DOIUrl":"10.1200/JCO.24.01119","url":null,"abstract":"<p><strong>Purpose: </strong>Continuous use of antiangiogenic agents has demonstrated survival benefits in various cancers. This trial aimed to compare the efficacy and safety of ramucirumab plus irinotecan with irinotecan monotherapy as a third- or later-line treatment for patients with advanced or recurrent gastric or gastroesophageal cancer (AGC) that has progressed on previous ramucirumab-based chemotherapy.</p><p><strong>Methods: </strong>Patients age 20 years and older with AGC, who had experienced disease progression during ramucirumab-based chemotherapy, were randomly assigned to receive either ramucirumab plus irinotecan or irinotecan monotherapy. The primary end point was overall survival (OS) expecting a hazard ratio (HR) of 0.77 (a power of 80% and a significance level of one-sided 0.05). Secondary end points included progression-free survival (PFS), response rate, disease control rate (DCR), and safety.</p><p><strong>Results: </strong>Between February 2017 and August 2022, 402 patients in Japan were randomly assigned to receive ramucirumab plus irinotecan (n = 202) or irinotecan monotherapy (n = 200). The median OS was 9.4 months in the combination arm and 8.5 months in the monotherapy arm, with an adjusted HR of 0.91 (95% CI, 0.74 to 1.12; <i>P</i> = .49). PFS was improved (median, 3.8 <i>v</i> 2.8 months; HR, 0.72 [95% CI, 0.59 to 0.89]; <i>P</i> = .002), while the DCR was significantly better (64.4% <i>v</i> 52.1%; <i>P</i> = .03) with the combination therapy. The adverse events of the combination therapy were manageable.</p><p><strong>Conclusion: </strong>Adding ramucirumab to irinotecan does not provide a significant advantage in OS over irinotecan alone in patients with AGC who have progressed during ramucirumab-containing chemotherapy.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2196-2207"},"PeriodicalIF":42.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132443","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":"Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory <i>KRAS</i> G12C Colorectal Cancer.","authors":"Filippo Pietrantonio, Lisa Salvatore, Taito Esaki, Dominik Paul Modest, David Paez Lopez-Bravo, Julien Taieb, Michalis V Karamouzis, Erika Ruiz-Garcia, Tae Won Kim, Yasutoshi Kuboki, Fausto Meriggi, David Cunningham, Kun-Huei Yeh, Emily Chan, Joseph Chao, Qui Tran, Chiara Cremolini, Marwan Fakih","doi":"10.1200/JCO-24-02026","DOIUrl":"10.1200/JCO-24-02026","url":null,"abstract":"<p><p>In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with <i>KRAS</i> G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). One hundred sixty patients were randomly assigned 1:1:1 to receive sotorasib 960 mg-panitumumab (n = 53), sotorasib 240 mg-panitumumab (n = 53), or investigator's choice (n = 54; crossover permitted after primary analysis). Overall survival (OS) analysis, a key secondary end point, although not adequately powered, was prespecified at 50% maturity (after approximately 80 deaths). In this study, we report the OS, updated overall response rates (ORRs), and data for safety. After a median follow-up of 13.6 months, 24, 28, and 30 deaths occurred in the sotorasib 960 mg-panitumumab, sotorasib 240 mg-panitumumab, and investigator's choice arms, respectively; updated objective response rates (ORRs; 95% CI) were 30.2% (95% CI, 18.3 to 44.3), 7.5% (95% CI, 2.1 to 18.2), and 1.9% (95% CI, 0.0 to 9.9), respectively. Compared with investigator's choice, the hazard ratios (HRs [95% CI]) for OS were 0.70 (95% CI, 0.41 to 1.18; two-sided <i>P</i> = .20) with sotorasib 960 mg-panitumumab and 0.83 (95% CI, 0.49 to 1.39; two-sided <i>P</i> = .50) with sotorasib 240 mg-panitumumab. No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory <i>KRAS</i> G12C mCRC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2147-2154"},"PeriodicalIF":42.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993885","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":"Adjuvant Treatment Options and Modalities in Pancreatic Adenocarcinoma: Insights From ESPAC4.","authors":"Halil Göksel Güzel, Arif Hakan Önder","doi":"10.1200/JCO-24-02707","DOIUrl":"10.1200/JCO-24-02707","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2228"},"PeriodicalIF":42.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752952","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":"BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203.","authors":"Iván Márquez-Rodas, Caroline Dutriaux, Philippe Saiag, Luis de la Cruz Merino, Eduardo Castañón Álvarez, Caroline Robert, Juan F Rodríguez-Moreno, Ana Arance, Pablo Cerezuela-Fuentes, Henri Montaudié, Miguel F Sanmamed, María González-Cao, Julie Charles, María Pilar López Criado, Alfonso Berrocal, Enrique de Miguel, Elisa Funck-Brentano, Sorilla Prey, Mᵃ Carmen Álamo de la Gala, Ignacio Melero, Jose Antonio Avilés-Izquierdo, Ruth Roman, Beatriz Garcia-Pelaez, Sonia Rodriguez, Zuzana Jirakova Trnkova, Marisol Quintero, Sonia Maciá, Marya F Chaney, Stephane Dalle","doi":"10.1200/JCO-24-02595","DOIUrl":"https://doi.org/10.1200/JCO-24-02595","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with anti-PD-1-resistant melanoma (MEL) have no well-defined standard of care. BO-112 is a synthetic, double-stranded RNA (poly I:C) nanoplexed with polyethylenimine that when administered intratumorally has showed in patients with solid tumors potential to revert this resistance. We report efficacy and safety of the phase II clinical trial of intratumoral BO-112 plus intravenous pembrolizumab for patients with anti-PD-1-resistant MEL (ClinicalTrials.gov identifier: NCT04570332).</p><p><strong>Methods: </strong>Forty-two patients were treated with intratumoral BO-112 once every week for 7 weeks and then once every 3 weeks (up to 2 mg and up to eight lesions per treatment) combined with 200 mg pembrolizumab once every 3 weeks until progressive disease, unacceptable toxicity, death, or up to 1 year. Primary end point was RECIST 1.1 objective response rate (ORR) by independent central radiology review in modified intention-to-treat population (mITT; patients evaluable for response) with 20% ORR positivity threshold. Secondary key end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety.</p><p><strong>Results: </strong>For mITT, there were 40 patients and the ORR was 25%, with 10% complete, 15% partial, and 40% stable disease, with nonachieved (NA) median DOR (95% CI, 8.3 to NA). For ITT, there were 42 patients, and the median PFS and OS were 3.7 months (95% CI, 2.2 to 9.2) and NA (95% CI, 9.9 to NA), respectively, with 54% patients alive at 24 months. The combination was well tolerated: 16 patients (38.1%) experiencing ≥G3-4 adverse events, four (9.5%) drug-related, and no deaths related to treatment.</p><p><strong>Conclusion: </strong>The clinical trial has met its primary end point (ORR) making BO-112 with pembrolizumab a potential strategy to revert anti-PD-1 resistance in patients with MEL. PFS results are in line with other clinical trials in anti-PD-1-resistant scenario, with promising OS data.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402595"},"PeriodicalIF":42.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512029","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":"Erratum: Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321).","authors":"Jeff P Sharman, Talha Munir, Sebastian Grosicki, Lindsey E Roeker, John M Burke, Christine I Chen, Norbert Grzasko, George Follows, Zoltán Mátrai, Alessandro Sanna, Lugui Qiu, Ru Feng, Vu Minh Hua, Wojciech Jurczak, Matthias Ritgen, Shuhua Yi, Francesc Bosch, Catherine C Coombs, Katherine Bao, Vishalkumar Patel, Bin Liu, Livia Compte, Ananya Guntur, Denise Y Wang, Marisa Hill, Ching Ching Leow, Paolo Ghia, Paul M Barr","doi":"10.1200/JCO-25-01356","DOIUrl":"https://doi.org/10.1200/JCO-25-01356","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501356"},"PeriodicalIF":42.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512030","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":"Erratum: Randomized, Open-Label, Phase III Study of Tilsotolimod in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced Refractory Melanoma (ILLUMINATE-301).","authors":"Adi Diab, Paolo A Ascierto, Michele Maio, Reham Abdel-Wahab, Sylvie Negrier, Laurent Mortier, Petr Arenberger, Stephane Dalle, Ivana Krajsova, Luis de la Cruz, Marie-Therese Leccia, Michele Guida, Celeste Lebbe, Jean-Jacques Grob, Marcus O Butler, Gino K In, Carmen Loquai, John W T Walker, Victoria Atkinson, Ellen Kapiteijn, Sebastian Haferkamp, Srinivas Chunduru, Shahram Rahimian, Massimo Guidoboni, Caroline Robert","doi":"10.1200/JCO-25-01412","DOIUrl":"https://doi.org/10.1200/JCO-25-01412","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501412"},"PeriodicalIF":42.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496806","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":"Enduring Economic Effects of a Cancer Diagnosis in Adolescence and Young Adulthood.","authors":"Danielle Novetsky Friedman,Bridgette Thom","doi":"10.1200/jco-25-01005","DOIUrl":"https://doi.org/10.1200/jco-25-01005","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"17 1","pages":"JCO2501005"},"PeriodicalIF":45.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487885","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}