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Aim: MET exon 14 (MET ex14) skipping occurs in 3-4% of non-small-cell lung cancer (NSCLC) cases. Low frequency of this alteration necessitated open-label, single-arm trials to investigate MET inhibitors. Since broad MET biomarker testing was only recently introduced in many countries, there is a lack of historical real-world data from patients with MET ex14 skipping NSCLC receiving conventional therapies. Given the rarity of this population and limitations of existing real-world data sources, the MOMENT registry aims to prospectively collect uniform, comprehensive, high-quality data from patients with MET ex14 skipping advanced NSCLC treated in routine clinical practice, which can support clinical and regulatory decision making. Patients & methods: MOMENT is a multinational, non-interventional disease registry collecting data on patients with MET ex14 skipping advanced NSCLC receiving any systemic anticancer therapy. Newly diagnosed patients and those already receiving treatment are eligible. Patients with previous participation in a clinical trial can be included if they receive at least one subsequent therapy line in a routine clinical setting. Eligible systemic treatment includes all available anticancer therapies (approved, conditionally approved or provided through Early Access). Data collection includes biomarker testing results, demographics, baseline clinical characteristics, treatment details and effectiveness, safety information and imaging. Registry site inclusion is dependent on confirmation that local MET ex14 skipping detection methods are sufficient to confirm MET ex14 skipping status. MOMENT is currently active at more than 60 sites across Europe and North America and approximately 700 patients are expected to be enrolled within the next 4 years. The first patient was enrolled on 4 October 2022. After completion of data collection, MOMENT data can be shared with external parties to conduct non-interventional studies. Discussion/conclusion: The MOMENT registry collects comprehensive, high-quality real-world data from patients with MET ex14 skipping advanced NSCLC receiving systemic anticancer treatment in a routine clinical setting, to enable future studies informing regulatory decisions and optimal care for this rare population. Clinical Trial Registration: NCT05376891 (ClinicalTrials.gov); EUPAS47602 (EU PAS register no.).

Idiopathic inflammatory myopathies (IIMs) are muscle disorders characterized by proximal weakness of the skeletal muscles, inflammation in muscle, and autoimmunity. The classic subgroups in IIMs include dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and polymyositis (PM). PM is increasingly recognized as a rare subtype and often included in overlap myositis, the antisynthetase syndrome when no rash is present, or misdiagnosed inclusion body myositis. Magnetic resonance imaging (MRI) has played an increasingly important role in IIM diagnosis and assessment. Although conventional MRI provides qualitative information that is helpful for diagnosis, its application for the quantitative assessment of disease activity is challenging. Therefore, advanced quantitative MRI techniques have been implemented in the past 10 years to highlight potential new applications of disease monitoring in IIM. The aim of this review is to examine the role of quantitative MRI techniques in evaluating the key imaging features of IIM, mainly muscle edema and muscle damage (fatty replacement and/or muscle atrophy)., Competing Interests: JP has received research support from ArgenX, Corbus Pharmaceuticals, Kezar Life Sciences, and Pfizer Inc.; consulting fees and/or honoraria from ArgenX, Alexion, EMD Serono, Guidepoint Consulting, Pfizer Inc., and Roivant Sciences, and is supported by grant number K23AR073927 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). LC-S has received clinical trial support paid to her institution from Pfizer Inc., Corbus, Kezar, Janssen, Horizon Therapeutics/Amgen, EMD Serono, Inc., Abcuro; has been a Steering Committee member for Janssen, Steritas; served as DSMB Chair for Galapagos; has received royalties for IP related to anti-HMGCR assay from Inova Diagnostics; and has received consulting fees paid to LC-K from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD Serono, Inc., ArgenX, Allogene, Pfizer Inc., Horizon Therapeutics/Amgen, Octapharma, NuVig, Immunovant, and Nkarta. MB has served on advisory boards for Image Analysis Group IAG, Radiobotics, Teal Medical, and Chondrometrics; is a consultant to and shareholder of IAG; and serves as an Editorial Board Member for Osteoarthritis Imaging. JC has received consulting fees from AstraZeneca and Covera Health; has served on advisory boards for Carestream, IAG and Image Biopsy Lab; and is Deputy Editor for Radiology, an Associate Editor for Arthritis and Rheumatology and an Editorial Board Member for Osteoarthritis Imaging. SE is an employee of Merck Serono Ltd., Feltham, UK, an affiliate of Merck KGaA. DD is an employee of EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. OK is an employee and shareholder of IAG. The authors declare that this study received funding from Merck KGaA. The funder reviewed an advanced draft of the manuscript, but was not involved in the concept development, the collection, analysis, and interpretation of data, the writing of this article, or the decision to submit it for publication., (Copyright © 2025 Paik, Christopher-Stine, Boesen, Carrino, Eggleton, Denis and Kubassova.)

Background and Aims: Simultaneous inhibition of the TGF-β and programmed cell death 1 ligand 1 pathways provides a potential novel treatment approach. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death 1 ligand 1, was evaluated in patients with advanced HCC., Approach and Results: In this global, open-label, phase I study (NCT02517398), patients with programmed cell death 1 ligand 1-unselected HCC who failed or were intolerant to ≥1 line of sorafenib received bintrafusp alfa 1200 mg every 2 weeks in a dose-escalation (n = 38) or dose-expansion (n = 68) cohort until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was the best overall response per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee. Secondary endpoints included investigator-assessed best overall response, safety, and pharmacokinetics. Median follow-up times (range) were 41.4 (39.8-44.2) and 38.6 (33.5-39.7) months in the dose-escalation and dose-expansion cohorts, respectively. The objective response rate was below the prespecified 20% objective response rate threshold set to evaluate the efficacy of bintrafusp alfa in both cohorts (10.5% and 8.8%, respectively). Median overall survival and progression-free survival, respectively, were 13.8 and 1.5 months in the dose-escalation cohort and 13.5 and 1.4 months in the dose-expansion cohort. Treatment-related adverse events occurred in 78.9% and 64.7% of patients in the respective cohorts (grade ≥3 in 18.4% and 25.0% of patients)., Conclusions: Bintrafusp alfa showed moderate clinical activity and a safety profile consistent with previous studies of bintrafusp alfa in patients with advanced HCC.

Introduction: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment., Methods: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator. On the basis of the recommendation of an independent data monitoring committee, the study was discontinued before the maturity of overall survival data (secondary end point)., Results: A total of 153 patients were randomized to either BA (n = 75) or durvalumab groups (n = 78). The median progression-free survival was 12.8 months versus 14.6 months (stratified hazard ratio = 1.48 [95% confidence interval: 0.69-3.17]), in the BA and durvalumab groups, respectively. Trends for overall response rate (29.3% versus 32.1%) and disease control rate (66.7% versus 70.5%) were similar between the two groups. Any-grade treatment-emergent adverse events occurred in 94.6% versus 96.1% of patients in the BA versus durvalumab groups, respectively. Bleeding events in the BA group were mostly grade 1 (21.6%) or 2 (9.5%)., Conclusions: BA with cCRT followed by BA exhibited no efficacy benefit over placebo with cCRT followed by durvalumab in patients with stage III unresectable NSCLC., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Patients treated with immune checkpoint inhibitors (ICIs) may experience pseudoprogression, which can be classified as progressive disease (PD) by Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and could lead to inappropriate treatment discontinuation. Immune-response criteria were developed to better capture novel response patterns seen with ICIs., Methods: We pooled data from 1765 patients with 12 types of advanced solid tumors treated with avelumab (an anti-programmed death ligand 1 (PD-L1) monoclonal antibody) monotherapy in the JAVELIN Solid Tumor and JAVELIN Merkel 200 trials, conducted a comparative analysis of tumor assessments by investigators according to RECIST 1.1 and immune-related RECIST (irRECIST), and evaluated the correlation between progression-free survival (PFS) and overall survival (OS)., Results: In total, 147 patients (8.3%) had a best overall response (BOR) of PD by RECIST 1.1 but had immune-related disease control by irRECIST (defined as immune-related BOR (irBOR) of immune-related stable disease or better). This discordance was seen irrespective of PD-L1 status and observed across all tumor types. Overall, PFS and immune-related PFS showed similar imputed rank correlations with OS., Conclusions: The use of irRECIST identified a subset of patients with a BOR of PD by RECIST 1.1 but an irBOR of immune-related disease control by irRECIST with a distinctive survival curve, thereby providing more clinically relevant information than RECIST 1.1 alone. However, as a surrogate endpoint for OS in the whole population, immune-related PFS by irRECIST did not show improved predictive value compared with PFS by RECIST 1.1., Competing Interests: Competing interests: JLG has received research funding from Astellas Medivation, Bavarian Nordic, Bristol Myers Squibb, EMD Serono, an affiliate of Merck KGaA, NantBioScience, and Pfizer. SPD has provided consultancy or advisory services for Amgen, GlaxoSmithKline, Immune Design, Incyte, EMD Serono, an affiliate of Merck KGaA, and Nektar Therapeutics, and received travel expenses from Adaptimmune, EMD Serono, an affiliate of Merck KGaA, and Nektar Therapeutics. JM is an employee of EMD Serono Research & Development Institute, Billerica, Massachusetts, USA, an affiliate of Merck KGaA. SPE is an employee of Merck Serono Ltd., Feltham, UK, an affiliate of Merck KGaA. MB is an employee of Merck. All other authors report no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Cetuximab in combination with chemotherapy is a standard-of-care first-line treatment regimen for patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC); however, the efficacy of cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX) has never before been proven in a controlled and randomized phase III trial. To our knowledge, the TAILOR trial ( ClinicalTrials.gov identifier: NCT01228734) is the first randomized, multicenter, phase III study of the addition of cetuximab to first-line FOLFOX prospectively choosing a RAS wt population and thus providing confirmative data for the efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone., Patients and Methods: TAILOR is an open-label, randomized (1:1), multicenter, phase III trial in patients from China comparing FOLFOX-4 with or without cetuximab in RAS wt ( KRAS / NRAS , exons 2 to 4) mCRC. The primary end point of TAILOR was progression-free survival time; secondary end points included overall survival time, overall response rate, and safety and tolerability., Results: In the modified intent-to-treat population of 393 patients with RAS wt mCRC, adding cetuximab to FOLFOX-4 significantly improved the primary end point of progression-free survival time compared with FOLFOX-4 alone (hazard ratio, 0.69; 95% CI, 0.54 to 0.89; P = .004; median, 9.2 v 7.4 months, respectively), as well as the secondary end points of overall survival time (current assessment after 300 events: hazard ratio, 0.76; 95% CI, 0.61 to 0.96; P = .02; median, 20.7 v 17.8 months, respectively) and overall response rate (odds ratio, 2.41; 95% CI, 1.61 to 3.61; P < .001; 61.1% v 39.5%, respectively). Treatment was well tolerated, and there were no new or unexpected safety findings., Conclusion: The TAILOR study met all of its objectives and relevant clinical end points, confirming cetuximab in combination with FOLFOX as an effective standard-of-care first-line treatment regimen for patients with RAS wt mCRC.

Introduction: The purpose of this study was to assess the efficacy and safety of FOLFOX4, comprising infusional 5-fluorouracil (5-FU)/leucovorin (LV) and oxaliplatin, with cetuximab compared with UFOX, comprising UFT, an oral prodrug of 5-FU, LV, and oxaliplatin, with cetuximab as first-line treatment for mCRC., Patients and Methods: Patients, unselected by tumor KRAS status, were randomized 1:1 to FOLFOX4 with cetuximab or UFOX with cetuximab. Treatment was continued until disease progression or unacceptable toxicity. The primary end point, assessed in the intention-to-treat population, was progression-free survival (PFS). Secondary end points included tumor response, overall survival, and safety. Outcome according to KRAS mutation status was investigated., Results: Recruitment was curtailed at 302 patients after reporting of the importance of tumor KRAS mutation status for cetuximab activity. Baseline characteristics were balanced between treatment groups. PFS was significantly longer in the FOLFOX4 with cetuximab group compared with UFOX with cetuximab group (median 8.2 vs. 6.6 months; hazard ratio, 0.68; 95% confidence interval [CI], 0.52-0.89; P = .0048). The response rate was also significantly greater in the FOLFOX4 with cetuximab group (51.3% vs. 37.5%, respectively; odds ratio, 1.76; 95% CI, 1.11-2.78; P = .0160), although overall survival was comparable. In the KRAS wild type subgroup, efficacy outcomes were similar to those in the intention-to-treat population. Side effect profiles were manageable and consistent with expectations., Conclusion: In the first-line treatment of mCRC, UFOX with cetuximab had an acceptable safety profile but inferior activity compared with FOLFOX4 with cetuximab in relation to PFS and response. The regimens were comparable with regard to overall survival., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To compare the efficacy of neoadjuvant (NA) docetaxel (DOC) with anthracycline-based therapy and determine the efficacy of NA DOC in patients with breast cancer initially failing to respond to anthracycline-based NA chemotherapy (CT)., Patients and Methods: Patients with large or locally advanced breast cancer received four pulses of cyclophosphamide 1,000 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.5 mg/m(2), and prednisolone 40 mg (4 x CVAP) for 5 days. Clinical tumor response was assessed. Those who responded (complete response [CR] or partial response [PR]) were randomized to receive further 4 x CVAP or 4 x DOC (100 mg/m(2)). All nonresponders received 4 x DOC., Results: One hundred sixty-two patients were enrolled; 145 patients completed eight cycles of NA CT. One hundred two patients (66%) achieved a clinical response (PR or CR) after 4 x CVAP. After randomization, 50 patients received 4 x CVAP and 47 patients received 4 x DOC. In patients who received eight cycles of CT, the clinical CR (cCR) and clinical PR (cPR) (94% v 66%) and pathologic CR (pCR) (34% v 16%) response rates were higher (P =.001 and P =.04) in those who received further DOC. Intention-to-treat analysis demonstrated cCR and cPR (85% v 64%; P =.03) and pCR (31% v 15%; P =.06). Axillary lymph node examination revealed residual tumor in 33% of patients who received 8 x CVAP and 38% of patients who received further DOC. In patients who failed to respond to the initial CVAP, 4 x DOC resulted in a cCR and cPR rate of 55% and a pCR rate of 2%. Forty-four percent of these patients had residual tumor within axillary lymph nodes., Conclusion: NA DOC resulted in substantial improvement in responses to DOC.

Background: Previous phase II studies of docetaxel have indicated that hepatic metastases from breast cancer respond well to first-line treatment with docetaxel. The objective of this prospective, open label phase II study therefore was specifically to evaluate the activity and safety of docetaxel in this indication., Patients and Methods: The study recruited 47 women (mean age 50 years, range 33-66 years) with hepatic metastases from breast cancer who fulfilled the eligibility criteria. After premedication with steroids, patients received a one-hour intravenous infusion of docetaxel 100 mg/m2 at three-weekly intervals for up to eight cycles. Response to treatment during medication was assessed after three, six and where appropriate, eight cycles and every three month follow-up thereafter, until disease progression or death., Results: The best overall response rate (ORR) for evaluable patients was 64.3% (95% CI: 48.0-78.5%). In terms of the primary efficacy parameters, the ORR at the sixth cycle of treatment was 62% (95% CI: 45%-80%) with 17% complete responses. The median duration of response was 139 days (95% CI: 111-216 days) and the median survival duration calculated on an intent-to-treat basis was 335 days (227-568 days, 95% CI). One (2%) toxic death was reported., Conclusions: Docetaxel is a highly effective cytotoxic agent in the treatment of patients with liver metastases from breast cancer.

Purpose: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal., Patients and Methods: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m(2) and docetaxel 75 mg/m(2)); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m(2) and docetaxel 85 mg/m(2))., Results: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months., Conclusion: Cisplatin and docetaxel can be administered at doses of 75 mg/m(2) and 75 mg/m(2), respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m(2) adds unacceptable hematologic toxicity and potential risks to the patient.

Background: Given as first- or second-line chemotherapy docetaxel appears to have great potential in advanced breast cancer., Patients and Methods: Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1-7). 342 patients (91%) had at least one prior anthracycline-based regimen., Results: Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients. 46% among the 299 patients who were anthracycline resistant and 35% among the 82 patients who were anthracycline refractory (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg m2 with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan-Meier survival analysis yielded a median survival of 194 days (95% CI: 178-218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis., Conclusions: The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an 'anthracycline refractory' population.