OBJECTIVE: Oral metronomic cyclophosphamide (OMC) implicates the daily administration of low doses of chemotherapy. Its antitumor activity combined with an oral administration route and a good toxicity profile makes OMC an attractive option for heavily pretreated patients. We retrospectively evaluated OMC\'s clinical benefit and objective response in recurrent ovarian cancer patients.
METHODS: This is a retrospective observational study involving patients treated with OMC (50 mg daily) from 2017 to 2022 at the Academic Division Gynaecology, Mauriziano Hospital, Torino, Italy. Clinical benefit assessment included CA125 response, radiological response, and reported symptomatic improvement. Toxicities were reported using Common Terminology Criteria for Adverse Events version 5.0.
RESULTS: Thirty-eight patients (average age 72, range 49-88) were included. 90% had FIGO stage III/IV at diagnosis and 64% underwent ≥ 3 previous lines of chemotherapy. Before OMC, 79% had ECOG 1 or 2. 8.6% of patients had a partial response (PR), and 40% a stable disease (SD). Median duration of response was 7.4 months. After 3 months on OMC, 51% experienced symptom improvement, and 53.3% experienced Ca125 reduction or stabilization. 66.7% of patients older than 75 responded to treatment; in 40% of cases, responses lasted ≥ 6 months (p = 0.08). No G3-4 hematological toxicities occurred. Nausea and fatigue G1-G2 were reported in 5 (13%) and 13 (34%) cases, respectively.
CONCLUSIONS: OMC is a feasible therapeutic option for recurrent ovarian cancer, providing satisfying clinical responses with a good toxicity profile, even in elderly and heavily pretreated patients with a suboptimal performance status.

BACKGROUND: Bone and soft tissue sarcomas are rare malignancies, and their heterogeneity has limited the development of novel drugs. This study aimed to apply two validated tools to evaluate the clinical benefits of novel drug therapies for sarcoma developed over the last decade.
METHODS: The PubMed and Embase databases were searched for randomized controlled trials (RCTs) of systemic therapies for sarcomas published between 2013 and 2023. Each trial was scored according to the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) and the American Society of Clinical Oncology-Value Framework version 2 (ASCO-VF).
RESULTS: We included 52 RCTs in this study, of which 17 (32.7%) reported positive results that favored the experimental arm. The ESMO-MCBS grades were determined in 14/17 positive trials, and three of them (21.4%) met the threshold for meaningful clinical benefit. Likewise, ASCO-VF scores were calculated for 11/17 positive trials, and three of them (27.3%) met the threshold for meaningful clinical benefit. Weak correlation (r = 0.38, P = 0.277) and agreement (κ = 0.211, P = 0.490) were observed between the two frameworks.
CONCLUSIONS: Only a few RCTs with positive results have demonstrated substantial patient benefits for bone and soft tissue sarcomas over the past decade.

BACKGROUND: Amivantamab, an EGFR-MET bispecific antibody, is the first approved targeted therapy for patients with EGFR Ex20ins NSCLC after prior platinum-based chemotherapy-a population with historically poor outcomes before amivantamab approval. As antitumor activity in single-arm studies typically focuses on responders, the evaluation of outcomes in patients with stable disease (SD) as best response is of clinical interest.
METHODS: Among 114 patients with post-platinum EGFR Ex20ins NSCLC in CHRYSALIS (NCT02609776; data cutoff: March 30, 2021), response was assessed by blinded independent central review via RECIST v1.1. Patients alive and receiving therapy at 12 weeks were grouped by response at this landmark: partial or complete response (PR+), SD, or progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) by response cohort were determined using the Kaplan-Meier method; hazard ratios (HRs) and 95% confidence intervals (CIs) between response cohorts were calculated using Cox proportional hazards regression.
RESULTS: Among patients alive and receiving therapy at 12 weeks (n=107), 42 (39%) had PR+, 52 (49%) had SD, and 13 (12%) had PD. Among patients with PR+ and SD, median PFS was 12.2 and 7.0 months, respectively. A corresponding improvement in OS was observed in patients achieving PR+ (median: not reached; HR vs PD=0.21 [95% CI: 0.08-0.54]) and SD (median: 23.0 months; HR vs PD=0.33 [95% CI: 0.14-0.77]), relative to those with PD (median: 14.0 months).
CONCLUSIONS: SD was observed in 49% of patients receiving amivantamab, with corresponding increases in OS that dramatically improved the prognoses of this patient population.

Children deserve to be treated with appropriate medicines based on robust assessments. Despite the introduction of new regulations, the availability of medicines for children is suboptimal because of the frequent lack of relevant clinical trials due to the difficulty of conducting such trials. Thus, the Transparency Committee (TC) of the French National Authority for Health, who oversees the assessment of medicinal products in France, set up a pediatric working group with two aims: (1) The first aim was to review all opinions on medicines for pediatric use. Out of 536 opinions delivered between 2020 and 2022, 181 (34 %) concerned medicines for pediatric use. Whereas oncology largely dominated the medicines for adults, medicines for infectious diseases, endocrinology/metabolism, neurology, and hematology mostly prevailed for children. (2) The second aim was to clarify the evaluation criteria assessed by the TC, namely, the clinical benefit (CB), the clinical added value (CAV), and the public health impact (PHI) for pediatric medicinal products. An important CB was given to 113 out of 161 (71 %) opinions on medicines for pediatric use when it concerned pathologies with a severe prognosis. The quality of the demonstration (e.g., double-blind randomized trial vs. placebo or another active medicine) played a major role in the CB level. Clinical pediatric studies were also consistently associated with higher CAV levels: levels I (major) to III (moderate) in 26 out of 42 (62 %) opinions, level IV (minor) and level V (no therapeutic progress) in 43 out of 84 (51 %) and 30 out of 43 (70 %) opinions granting a sufficient CB, respectively. Conversely, 22 out of 30 (73 %) dossiers based only on literature reviews were given a level V. The main criteria leading to the qualification of a medicine for pediatric use as providing a PHI included a significant change in the morbidity and mortality of the disease and an improvement in the care pathway. Assessments were mostly aligned on the adults in the case of subsequent extensions of indications to children. Lastly, new measures were taken aimed at shortening median delays in the assessment process in order to reduce off-label use of medicines in France.

Introduction Abdominal angiography procedures such as transarterial chemoembolization (TACE) are essential for hepatocellular carcinoma treatment. One method commonly used is transfemoral access (TFA). However, issues associated with this method, which include postoperative compression of the puncture site and long periods of bed rest, can affect patient satisfaction. Thus, transradial access (TRA), a minimally invasive treatment method that improves treatment quality, was developed for TACE. This retrospective, multicenter study aimed to investigate the efficacy and safety of abdominal angiography using the radial artery approach. Methods In total, 1,601 patients underwent abdominal angiography using TRA and received treatment (radial access for visceral intervention (RAVI)) at 14 institutions in Japan. The treatment time, procedure completion rate, patient satisfaction, and complications were investigated. Results The success rate of RAVI was 99.4%, and the complication rate was 1.2%. Approximately 98.2% of the patients requested the radial artery approach again. There were no significant differences in the success rate of RAVI and the incidence of complications based on the operator\'s years of experience or the patient\'s age. Some patients developed minor complications such as puncture site bleeding, hematoma, vascular pain, and vasospasm. Further, serious complications (cerebral infarction (n = 1), cerebellar infarction (n = 1), and aortic dissection (n = 1)) were observed. Conclusion Similar to the conventional TFA, RAVI helped in facilitating peritoneal angiography safely. In abdominal angiography, this method can reduce patient burden and can be widely used in the future from the perspective of clinical benefit.

BACKGROUND: The study evaluates the first-line application of pembrolizumab in metastatic non-small-cell lung cancer (mNSCLC), head and neck squamous cell cancer (HNSCC), gastric cancer, and renal cell carcinoma. Utilizing the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the American Society of Clinical Oncology Value Framework (ASCO-VF), the analysis incorporates data from pivotal KEYNOTE trials.
METHODS: The study systematically assessed the clinical benefit of pembrolizumab in advanced solid malignancies through nine randomized controlled trials, one of which comprised two experimental arms. Data extraction from primary sources was conducted from PubMed, ASCO, and ESMO publications. Utilizing ESMO-MCBS and ASCO-VF forms, the evaluation focused on clinical benefit, toxicity, and bonus points, with discrepancies resolved through consensus discussions.
RESULTS: Nine first-line indications for pembrolizumab received Food and Drug Administration approval for metastatic solid tumors between 2018 and 2023. Notable distinctions in ESMO-MCBS grades revealed seven trials with substantial clinical benefit (grades 5 to 4) and three with moderate to negligible benefit (grades 3 to 1). Bonus points, primarily based on the tail of the curve, were allocated to three trials for overall survival, one for progression-free survival, and one for a significant improvement in quality of life.
CONCLUSIONS: Our evaluation of pembrolizumab across diverse cancers, especially in mNSCLC and HNSCC, revealed varied outcomes and challenges in clinical benefit interpretation. The assessment of clinical benefit, incorporating quantitative and qualitative endpoints, underscores the need to consider survivorship outcomes and patient perspectives for a comprehensive understanding.

UNASSIGNED: The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors.
UNASSIGNED: By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures.
UNASSIGNED: A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, p < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, p < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities.
UNASSIGNED: Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.

Paclitaxel, one of the most frequently used anticancer drugs, is dosed by body surface area, which leads to substantial inter-individual variability in systemic drug exposure. We evaluated clinical evidence regarding the scientific rationale and clinical benefit of individualized paclitaxel dosing based on measured systemic concentrations, known as therapeutic drug monitoring (TDM). In retrospective studies, higher systemic exposure is associated with greater toxicity and efficacy of paclitaxel treatment across several disease types and dosing regimens. In prospective trials, TDM reduces variability in systemic exposure, and has been demonstrated to reduce toxicity while retaining treatment efficacy for 3-weekly dosing in patients with advanced non-small cell lung cancer. Despite the demonstrated benefits of paclitaxel TDM, clinical adoption has been limited due to the challenges with sample collection and analysis. Based on our review, we strongly recommend TDM for patients receiving every 3-week paclitaxel in combination with a platinum agent for advanced NSCLC, due to the prospectively demonstrated clinical benefits, and find moderate evidence to recommend TDM for paclitaxel 3-hour infusions for other tumor types and preliminary evidence suggesting potential usefulness for paclitaxel administered by 1-hour infusions.

BACKGROUND: In the Netherlands, the clinical benefit of systemic anti-cancer treatments (SACTs) is assessed by the Committee for the Evaluation of Oncological Agents (cieBOM). For non-curative SACTs, the assessment is based on the hazard ratio (HR) for progression-free survival and/or overall survival (OS), and the difference in median survival. We evaluated the impact of different thresholds for effectiveness by reassessing the clinical benefit of SACTs.
METHODS: We reassessed SACTs that were initially assessed by cieBOM between 2015 and 2017. Four scenarios were formulated: replacing an \"OR\" approach (initial assessment) by an \"AND\" approach (used in all scenarios), changing the HR threshold from < 0.70 (initial assessment) to < 0.60, changing the threshold for the difference in median survival from > 12 weeks (initial assessment) to > 16 weeks, and including thresholds for OS rates. The outcomes of these scenarios were compared to the outcomes of the initial assessment.
RESULTS: Reassessments were conducted for 41 treatments. Replacing the \"OR\" approach by an \"AND\" approach substantially decreased the number of positive assessments (from 33 to 22), predominantly affecting immunotherapies. This number further decreased (to 21 and 19, respectively) in case more restrictive thresholds for the HR and difference in median survival were used. Including thresholds for OS rates slightly mitigated the impact of applying an \"AND\" approach.
CONCLUSIONS: The scenario-specific thresholds had a substantial impact; the number of negative assessments more than doubled. Since this was not limited to treatments with marginal survival benefits, understanding the potential challenges that may arise from applying more restrictive thresholds is essential.

OBJECTIVE: This study aims to estimate changes in the value of oncology drugs over time from initial data of the reimbursement decisions to subsequent publications in Korea, using two value frameworks.
METHODS: We retrieved primary publications assessed for reimbursement between 2007 and July 2021 from the decision documents of Health Insurance Review and Assessment and subsequent publications made available following reimbursement decision from ClinicalTrials.Gov and PubMed databases. Changes in the clinical benefit scores were assessed using the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). A paired t test was performed to test whether there was a difference in the scores between primary and subsequent publications.
RESULTS: Of 73 anticancer product/indication pairs, 45 (61.6%) had subsequent publications, of which 62.5% were released within 1 year of reimbursement decision. The mean ESMO-MCBS and ASCO-VF Net Health Benefit scores increased from primary to subsequent publications, although the differences were not significant. The mean ASCO-VF bonus score significantly increased from 15.91 to 19.09 (p = 0.05). The ESMO-MCBS and bonus scores increased by 0.25 and 0.21, respectively, and the bonus score had a greater impact on the ESMO-MCBS score than the preliminary score did.
CONCLUSIONS: The value of drugs demonstrated in subsequent publications varies considerably among oncology drugs, depending on uncertainty associated with the initial evidence and the availability of updated evidence. As decision-making in the face of uncertainty becomes more prevalent, the value frameworks can serve as simple screening tools for re-evaluation in these cases.