The Lancet Oncology最新文献

{"title":"Health-related quality of life in patients with KRASG12C-mutated chemorefractory metastatic colorectal cancer treated with sotorasib plus panitumumab or standard of care (CodeBreaK 300): results from a phase 3, randomised clinical trial","authors":"Dominik Paul Modest, Marwan Fakih, Lisa Salvatore, Taito Esaki, David Páez Lopez-Bravo, Julien Taieb, Michalis Karamouzis, Erika Ruiz-Garcia, Tae Won Kim, Yasutoshi Kuboki, Fausto Meriggi, David Cunningham, Kun-Huei Yeh, Chiara Cremolini, Qui Tran, Emily Chan, Joseph Chao, Istvan Matyas Majer, Filippo Pietrantonio","doi":"10.1016/s1470-2045(25)00352-3","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00352-3","url":null,"abstract":"<h3>Background</h3>In the phase 3 CodeBreaK 300 study, sotorasib (KRAS<sup><em>G12C</em></sup> inhibitor) plus panitumumab (EGFR inhibitor) significantly prolonged progression-free survival versus investigator's choice of trifluridine–tipiracil or regorafenib (standard of care) in patients with <em>KRAS</em><sup><em>G12C</em></sup>-mutated chemorefractory metastatic colorectal cancer. This analysis evaluated patient-reported outcomes (PROs) as secondary and exploratory endpoints.<h3>Methods</h3>In this open-label, randomised clinical trial, adult (aged ≥18 years) patients from 67 centres in 13 countries in Asia, Australia, Europe, and North America with <em>KRAS</em><sup><em>G12C</em></sup>-mutated chemorefractory metastatic colorectal cancer (as assessed by central molecular testing of tumour biopsy specimens) who were KRAS<sup><em>G12C</em></sup> inhibitor-naive, had progressed to recurrence after previous therapy with fluoropyrimidine, oxaliplatin, and irinotecan, with measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1, and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2, were enrolled. Patients were randomly assigned 1:1:1 using interactive response technology to receive sotorasib 960 mg (daily, orally)–panitumumab (6 mg/kg every 2 weeks, intravenous infusion), sotorasib 240 mg (daily, orally)–panitumumab (6 mg/kg every 2 weeks, intravenous infusion), or investigator's choice of trifluridine–tipiracil (35 mg/m<sup>2</sup> [up to 80 mg per dose] on days 1–5 and 8–12 twice a day, orally) or regorafenib (160 mg daily for the first 21 days, orally). Randomisation was stratified by by previous anti-angiogenic therapy, time from initial diagnosis of metastatic disease to randomisation, and ECOG performance status. The primary endpoint was progression-free survival (reported previously). PROs included fatigue at its worst according to the Brief Fatigue Inventory, pain at its worst according to the Brief Pain Inventory (where lower score is better), and Global Health Status–Quality of Life (GHS–QoL) and physical function subscales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (where higher score is better) assessed via validated PRO questionnaires, administered at baseline, day 1 of each 4-week cycle until disease progression, and safety follow-up. Analyses were conducted in a modified intention-to-treat population. Least squares mean changes from baseline to week 9 were estimated using a mixed effects model for repeated measures. Time to deterioration (TTD), change in overall status, and patient-reported tolerability were also evaluated as prespecified exploratory outcomes. TTD was summarised using a stratified Cox proportional hazards model and Kaplan–Meier curve. Change in overall status and patient-reported tolerability were also summarised descriptively over time. The study is registered with <span><span>Clinic","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kenya adopts digitally enabled cancer-care model","authors":"Paul Adepoju","doi":"10.1016/s1470-2045(25)00483-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00483-8","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strength of evidence supporting cancer drug approvals in China between 2017 and 2021: a retrospective analysis","authors":"Yichen Zhang, Dingyi Chen, Mengyuan Fu, Luwen Shi, Huseyin Naci, Anita K Wagner, Joseph S Ross, Xiaodong Guan","doi":"10.1016/s1470-2045(25)00329-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00329-8","url":null,"abstract":"<h3>Background</h3>Well designed pivotal clinical trials can provide robust evidence for the market authorisation of new cancer drugs, whereas lower-quality clinical evidence leads to uncertainty about drug benefits and harms. We aimed to investigate the strength of evidence supporting new cancer drug indications approved in China from 2017 to 2021.<h3>Methods</h3>In this retrospective analysis, we searched publicly available data from the National Medical Products Administration website to identify pivotal pre-approval efficacy trials supporting all original and supplemental cancer drug indications approved in China from Jan 1, 2017, to Dec 31, 2021. We included small molecules and biologics, and excluded traditional Chinese medicines, prophylactic vaccines, and generic or biosimilar versions of previously approved drugs. We collected trial protocols and publications from <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, PubMed, and the China National Knowledge Infrastructure database. The primary outcome was the strength of the supporting pivotal studies, as measured by study design (randomised or single-arm) and quality. For study quality, we evaluated the ability of single-arm trials to minimise bias, measured via the adoption of external control arm and adjusted confounders, and the risk of bias in randomised controlled trials (RCTs), evaluated with the revised Cochrane tool for risk-of-bias assessment. We also used ratio of hazard ratios (RHR) to quantify differences in effect size in RCTs with different risks of bias.<h3>Findings</h3>We found 77 novel cancer drugs for 86 original and 62 supplemental indications that were approved in China during the study dates, based on data from 205 pivotal studies. 44 (30%) indications were supported by single-arm trials only and 104 (70%) were supported by at least one RCT. Of the 54 pivotal single-arm trials with regulatory review documents, six (11%) used aggregated data from earlier trials as external controls, without adjustment for confounders. Of the 128 pivotal RCTs with published results, 47 (37%) were assessed as having some concern and 48 (38%) as having a high risk of bias. Overall, 149 (82%) of 182 pivotal trials that were assessable for quality had limitations in bias control. RCTs with some concern or high risk of bias in the randomisation process had smaller effect sizes (RHR 0·678 [95% CI 0·532–0·864]), and those with some concern or high risk of bias in missing outcome data had larger effect sizes (1·114 [1·004–1·237]), compared with RCTs with low risk of bias in these domains.<h3>Interpretation</h3>Four-fifths of assessable pivotal studies supporting new cancer indication approvals in China from 2017 to 2021 had weaknesses in design, conduct, or reporting that introduced uncertainty to the esti","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of high-quality evidence supporting cancer drug approvals","authors":"Kerstin N Vokinger","doi":"10.1016/s1470-2045(25)00361-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00361-4","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"734 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[68Ga]Ga-FAPI-46: an imaging biomarker for FAP-positive tumours","authors":"Roberto C Delgado Bolton, Adriana K Calapaquí Terán, Francesco Giammarile","doi":"10.1016/s1470-2045(25)00370-5","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00370-5","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[68Ga]Ga-FAPI-46 PET accuracy for cancer imaging with histopathology validation: a single-centre, single-arm, interventional, phase 2 trial","authors":"Kim M Pabst, Manuel M Weber, Christina Laschinsky, Patrick Sandach, Timo Bartel, Alina T Küper, Lukas Kessler, Marija Trajkovic-Arsic, Markus Eckstein, Elena Gilman, Michael Nader, Francesco Barbato, Lars E Podleska, Boris A Hadaschik, Rainer Hamacher, David Kersting, Nicola von Ostau, Bastian von Tresckow, Hans-Peter Kaelberlah, Claudia Kesch, Wolfgang P Fendler","doi":"10.1016/s1470-2045(25)00299-2","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00299-2","url":null,"abstract":"<h3>Background</h3>The fibroblast activation protein α (FAP)-directed radiotracer [<sup>68</sup>Ga]Ga-FAPI-46 for PET–CT has shown promising diagnostic accuracy in cancer staging in retrospective studies. We aim to investigate the positive predictive value (PPV) of [<sup>68</sup>Ga]Ga-FAPI-46 PET for detecting FAP-expressing tumours and the potential association between PET radiotracer uptake intensity and immunohistochemical FAP expression.<h3>Methods</h3>This single-centre, single-arm, interventional, phase 2 trial was conducted at the University Hospital Essen, Essen, Germany. Adults aged 18 years or older undergoing initial staging or restaging were eligible if they had at least one measurable tumour lesion (>1 cm) and a confirmed or suspected diagnosis of breast cancer, colorectal cancer, endometrial cancer, oesophageal cancer, head and neck cancer, ovarian cancer, pancreatic ductal adenocarcinoma (PDAC), prostate cancer, thyroid cancer, glioma, hepatocellular carcinoma, lymphoma, multiple myeloma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), sarcoma, seminoma, cancer of unknown primary origin, or other tumour types; had a planned or recent surgery or biopsy within 8 weeks before or after enrolment; and an ECOG performance status of 2 or less. Key exclusion criteria were previous external beam radiotherapy to the target lesion and receiving systemic cancer therapy within 1 month before enrolment. PET–CT images were acquired at a median of 11 min (IQR 10–14) after an intravenous injection of a median of 145 Megabecquerel (MBq; 124–154) of [<sup>68</sup>Ga]Ga-FAPI-46 and analysed by three independent, masked readers. The study concluded on day 30 of follow-up if histopathological confirmation and archived tumour tissue were already available, or on the day of biopsy or surgery within 8 weeks of receiving [<sup>68</sup>Ga]Ga-FAPI-46 PET–CT. Immunohistochemical FAP expression (score 0–3) was evaluated by an independent masked pathologist. The primary endpoint was the PPV of [<sup>68</sup>Ga]Ga-FAPI-46 PET for detecting immunohistochemical FAP-positive tumours (histopathologically confirmed) on a per-patient and per-region basis, with a predefined threshold of PPV of at least 75%, analysed in the intention-to-treat population. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT05160051</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is complete.<h3>Findings</h3>Between Dec 1, 2021, and Feb 6, 2024, 158 eligible participants were enrolled and three were excluded. 98 (63%) of 155 participants who received [<sup>68</sup>Ga]Ga-FA","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concerns over future of US health advisory panel under RFK Jr","authors":"Elizabeth Gourd","doi":"10.1016/s1470-2045(25)00468-1","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00468-1","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"US aid cuts affect vulnerable populations in the Democratic Republic of the Congo and Kenya","authors":"Sharmila Devi","doi":"10.1016/s1470-2045(25)00469-3","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00469-3","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and predictive value of baseline PSMA-PET total tumour volume and SUVmean in metastatic castration-resistant prostate cancer in ENZA-p (ANZUP1901): a substudy from a multicentre, open-label, randomised, phase 2 trial","authors":"Louise Emmett, Nathan Papa, Shalini Subramaniam, Megan Crumbaker, Andrew Nguyen, Anthony M Joshua, Shahneen Sandhu, Andrew Weickhardt, Sze-Ting Lee, Siobhan Ng, Roslyn J Francis, Jeffrey C Goh, David A Pattison, Thean Hsiang Tan, Ian D Kirkwood, Narjess Ayati, Claire Niu, Michael S Hofman, Andrew James Martin, Hayley Thomas, Shikha Sharma","doi":"10.1016/s1470-2045(25)00339-0","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00339-0","url":null,"abstract":"<h3>Background</h3>Quantitative parameters derived from gallium-68 [<sup>68</sup>Ga]Ga-prostate-specific membrane antigen (PSMA)-11 PET-CT (PSMA-PET-CT) such as whole-body standardised uptake value (SUV)mean and total tumour volume (PSMA-TTV) have shown prognostic value for response to lutetium-177 [<sup>177</sup>Lu]Lu-PSMA-617 monotherapy in patients with prostate cancer. Adding [<sup>177</sup>Lu]Lu-PSMA-617 to enzalutamide improved overall survival compared with enzalutamide in patients with metastatic castration-resistant prostate cancer in the ENZA-p trial. This prespecified substudy of ENZA-p evaluated baseline PSMA-PET quantitative parameters as predictive and prognostic biomarkers for enzalutamide plus [<sup>177</sup>Lu]Lu-PSMA-617 and enzalutamide monotherapy.<h3>Methods</h3>ENZA-p was an open-label, randomised, phase 2 trial done in 15 hospitals in Australia. Participants were aged 18 years or older with progressive metastatic castration-resistant prostate cancer who had not previously been treated with docetaxel or androgen receptor pathway inhibitors (abiraterone permitted) for metastatic castration-resistant prostate cancer, had [<sup>68</sup>Ga]Ga PSMA-PET-CT-positive disease, an Eastern Cooperative Oncology Group performance status of 0–2, and at least two risk factors for early progression on enzalutamide. Patients were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to either enzalutamide 160 mg daily (oral) or enzalutamide 160 mg daily plus adaptive-dosed (two or four doses) intravenous [<sup>177</sup>Lu]Lu-PSMA-617 7·5 GBq every 6–8 weeks. The primary endpoint was prostate-specific antigen (PSA) progression-free survival, which has been reported previously. All participants underwent baseline [<sup>68</sup>Ga]Ga-PSMA-11 PET-CT to assess eligibility (SUVmax >15 at a single site and SUVmax >10 at all larger tumour sites). PSMA-PET parameters were quantified with semi-automated software to derive PSMA-TTV and SUVmean and correlated with overall and PSA progression-free survival in a prespecified analysis, with the primary endpoint of this substudy being overall survival. Thresholds were based on SUVmean highest quartile (Q4 <em>vs</em> Q1–3) and PSMA-TTV median at baseline. We used the Kaplan–Meier method and Cox regression models and analysed patients on a treatment received basis. The trial is registered with ClinicalTrials.gov, NCT04419402, and follow-up is complete.<h3>Findings</h3>Between Aug 17, 2020, and July 26, 2022, 162 participants were randomly assigned to enzalutamide (n=79) or enzalutamide plus [<sup>177</sup>Lu]Lu-PSMA-617 (n=83). This substudy included the 160 of the 162 randomly assigned patients who received study treatment (79 in the enzalutamide group and 81 in the enzalutamide plus [<sup>177</sup>Lu]Lu-PSMA-617 group). Median follow-up at the final data cutoff (July 31, 2024) was 34 months (IQR 29–39), with 96 overall survival events (53 with enzalutam","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reflections on the PEACE V–STORM trial – Authors' reply","authors":"Piet Ost, Thomas Zilli","doi":"10.1016/s1470-2045(25)00423-1","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00423-1","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}