First-line Treatment For Patients Research Articles

The role of immune checkpoint inhibitors in the first-line treatment for patients with advanced biliary tract cancer: a systematic review and meta-analysis of randomized trials

The role of immune checkpoint inhibitors in the first-line treatment for patients with advanced biliary tract cancer: a systematic review and meta-analysis of randomized trials

Real-world effectiveness of first-line azacitidine or decitabine with or without venetoclax in acute myeloid leukemia patients unfit for intensive therapy.

First-line treatment in patients with acute myeloid leukemia (AML) unfit for intensive therapy is the combination of a hypomethylating agent (HMA) with venetoclax (VEN). However, retrospective data confirming the benefits of this regimen outside of clinical trials have shown conflicting results. We performed a multicenter retrospective analysis of outcomes with first-line HMA-VEN versus HMA in AML patients unfit for intensive chemotherapy. A total of 213 patients were included from three German hospitals (125 HMA-VEN, 88 HMA). Median overall survival in the HMA-VEN cohort was 7.9 months (95% confidence interval [CI], 5.1-14.7) versus 4.9 months (3.1-7.1) with HMA. After 1 year, 42% (95% CI, 33-54) and 19% (12-30) of patients were alive, respectively (hazard ratio [HR] for death, 0.64; 95% CI, 0.46-0.88). After adjusting for clinical and molecular baseline characteristics, treatment with HMA-VEN remained significantly associated with both prolonged survival (HR, 0.48; 95% CI, 0.29-0.77) and time to next treatment (HR, 0.63; 95% CI, 0.47-0.85). Patients who achieved recovery of peripheral blood counts had a favorable prognosis (HR for death, 0.52; 95% CI, 0.33-0.84). These data align with findings from the pivotal VIALE-A trial and support the use of HMA-VEN in patients unfit for intensive therapy.

Radiation exposure of patients undergoing transcatheter aortic valve implantation and factors contributing to it

Abstract Background/ Introduction Aortic stenosis (AS) is a calcific disease which affects the aortic valve leaflets and is commonly prevalent in people who are 65 years and older. The global burden of AS is expected to keep on increasing due to the longer life expectancy as well as the morbidity and mortality associated with the disease. Transcatheter aortic valve implantation is utilised for the management of AS. Currently, TAVI is recommended as a first-line treatment for patients who are 75 years and older and those who are at an intermediate to high surgical risk, with the aim of becoming the first treatment option for patients who are 65 years and older. However, one of the concerns of TAVI is the need of ionising radiation during valve placement. The study of exposure to ionising radiation in the TAVI population is becoming progressively more important to consider due to the broader population being considered and the long-term effects related to radiation. Purpose Locally there was no data available covering this topic, thus the aim of the study was to quantify the radiation dose that patients receive during TAVI procedures and to determine any procedural and patient factors that contribute to this radiation dose. Methods Retrospective data analysis was performed for procedures effected between January 2019 and December 2022. All the patients that underwent a transfemoral (TF) TAVI and fit within the inclusion criteria were included in the study. The data was collected from medical databases and underwent a process of data cleaning before information relating to patient and procedural characteristics was extracted. Data about percutaneous coronary interventions (PCI) that were performed during the same time period by the same operators was collected for comparison purposes. Results In total the data of 241 TAVI patients was analysed. Dose Area Product (DAP) was the main radiation metric utilised to quantify the radiation dose. Non-parametric statistical tests were performed due to right-skewedness. The median (IQR) DAP for these procedures was 9000 cGym2 (5975-13150) and the median (IQR) fluoroscopy time was 18.25 minutes (15, 23.5). The years 2019 and 2020 had the lowest median DAP. The DAP obtained in this study is lower than the European DRLs of 13000 cGym2. The median (IQR) DAP (5320cGym2 (2385-9860)), and fluoroscopy time (13.75 mins (8.25-21.62)) for PCIs were lower than for TAVI and this difference is statistically significant (P = <0.001). DAP was not significantly related only to age category and the operator’s combination. Generalised linear models (GLM) showed that prosthetic valve size, body surface area (BSA) and aortic valve gradient are statistically significant predictors of DAP. Conclusion This study shows that the local TAVI patients receive a radiation dose which is within acceptable European limits and that valve size and patient’s BSA are the variables that impacted the radiation dose.

Efficacy of Ipilimumab and Nivolumab in Patients with Melanoma and Brain Metastases—A Danish Real-World Cohort

Combination immunotherapy using ipilimumab/nivolumab is the golden standard treatment for patients with melanoma and asymptomatic brain metastases (MBM). However, it remains uncertain if real-world patients have the same treatment effects compared to patients enrolled in clinical trials. The aim of this study was to compare clinical benefits between real-world patients and patients enrolled in clinical trials when administering ipilimumab/nivolumab in treatment-naive patients with asymptomatic MBM. Using data from the Danish Metastatic Melanoma Database (DAMMED), 79 patients with clinical parameters similar to the inclusion criteria from two phase II trials, the ABC and the CheckMate-204 trials, were included in the analyses. Thirteen patients (16.5%) achieved complete response (CR) and an overall response rate (ORR) of 46.9%. We found an overall 6-month Progression-Free Survival (PFS) rate of 53.5% and a median PFS of 6.5 months. Median overall survival (mOS) was not reached during the 5-year follow-up. These results were comparable to the phase II trials. In conclusion, clinical benefits from phase II studies were comparable to Danish real-world data regarding OS, PFS, and CR. Confirming that combination immunotherapy can be recommended as first-line treatment for patients with asymptomatic, treatment-naive melanoma brain metastases.

Integration of the PD-L1 inhibitor atezolizumab and WT1/DC vaccination into standard-of-care first-line treatment for patients with epithelioid malignant pleural mesothelioma-Protocol of the Immuno-MESODEC study.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms' tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8-10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8-10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial's primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.

Regorafenib plus FOLFIRINOX as first-line treatment for patients with RAS-mutant metastatic colorectal cancer (FOLFIRINOX-R trial): a dose-escalation study.

The combination of bevacizumab and FOLFIRINOX is used in patients with RAS-mutant metastatic colorectal cancer (RASm-mCRC). Regorafenib, an oral multi-tyrosine kinase inhibitor, has antiangiogenic properties, cytostatic effects and also true cytotoxic effects, unlike bevacizumab. The aim of this study was to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of the regorafenib-FOLFIRINOX combination in patients with RASm-mCRC. The FOLFIRINOX-R trial was a phase 1/2 study where the dose-escalation part (3 + 3 design with three dose levels, DLs) was completed before its early termination. FOLFIRINOX (14-day cycle) included oxaliplatin (standard dose), folinic acid, fluorouracil and irinotecan (150 or 180mg/m²). Regorafenib (120 or 160mg daily) was given from day 4 to day 10 of each cycle. Dose-limiting toxicity (DLT) was studied in the first three cycles. Eligibility criteria included ECOG performance status ≤ 1 and not previously treated RASm-mCRC. Thirteen patients (median age: 65 years; min-max: 40-76) were enrolled. DLT could not be evaluated in one patient (DL3) due to poor observance. The median treatment duration and median follow-up were 6.2 (min-max: 2.3-10) and 13.4 (min-max: 3.8-18.0) months, respectively. Dose was modified in 12/13 (92%) patients. One grade 3 hypokalemia occurred at DL2. MTD was not reached at DL3. Grade 3 diarrhea was recorded in 7/13 patients (13 events) equally distributed in all DLs. The RP2D for this regorafenib-FFX combination could not be determined due to a high prevalence of grade 3 diarrhea related to treatment as advised by our Independent Data Monitoring Committee. ClinicalTrials.gov : NCT03828799.

Clinical outcomes of ablation of gastric dysplasia with argon plasma coagulation.

Although several small cohort studies have shown the utility of argon plasma coagulation (APC) in the treatment of gastric dysplasia, its clinical significance has not been established. This study aims to assess the efficacy of APC as a first line treatment for gastric dysplasia, and identify risk factors for residual dysplasia. A total of 179 cases of gastric dysplasia were treated with APC and have been followed-up with upper endoscopy within 1 year. The overall incidence and the characteristics of lesions with residual dysplasia in follow-up endoscopy were analyzed by logistic regression. Among 179 lesions treated with APC, 171 (95.5%) lesions have achieved complete ablation in the follow-up endoscopy. Additional APC was applied for residual dysplasia, achieving complete ablation in 97.77% (175/179). The upper third location of the gastric dysplasia was significantly associated with residual dysplasia, while tumor size, horizontal location, macroscopic morphology and grade of dysplasia showed no significant associations with residual dysplasia following the initial APC. APC with meticulous follow-up can be recommended as a first line treatment in patients with gastric dysplasia.

Evaluation of Sleep EEG Changes in Paediatric Patients with Language Dysfunction: A Follow Up Study

Abstract Background Several case reports and studies have described an association between sleep epileptiform discharges and language dysfunctions. This has been partly confirmed in studies that have investigated the effect of this epileptiform discharges on neurocognitive function. Objectives To screen for sleep-potentiated epileptiform discharges in children with language dysfunction (language delay or regression) and to evaluate the effect of treatment of these epileptiform discharges on language dysfunction. Methods The study was conducted on 93 children with language delay or language regression. Patients were recruited from the pediatric neurology clinic, pediatric outpatient clinic, phoniatrics outpatient clinic and the inpatient neurology ward at the Ain Shams University Children’s hospital, Cairo, Egypt in the period between February 2020 and November 2021. A 90- minute sleep electroencephalography, intelligence quotient level and language age were done for all patients included in the study. Children who had an active electroencephalography with uncontrolled clinical seizures or persistently epileptogenic activity without clinical seizures received treatment according to type of activity then after 6 months they were subjected to follow up electroencephalographyand assessment of intelligence quotient level and language age. Results The enrolled patients were divided into two groups: Group (1) including 28 (30%) patients with either or both of epileptogenic activity and clinical seizures and group (2) including 65 (70%) patients without either epileptogenic activity or clinicalseizures. We found 24 (85.7 %) children in group 1 had clinical seizures with median age of onset 2.5 years (range from 1-8 years). Further in the first group, 21 (85.7 %) of children showed presence ofepileptogenic activity with 10 (47.6 %) of children showed spike and slow wave, 6 (28.6 %) showed sharp wave, 3 (14.3 %) showed continuous spike and wave during slow wave sleep (CSWS), 2 (9.5 %) children showed sharp and slow wave. In our study, levetiracetam was given as first line treatment in patients with active seizures. An add-on therapy was given in patients who were not controlled on one antiepileptic drug. A follow up 90 minutes sleep electroencephalography was done and showed a highly significant reduction in epileptogenic activity with a p value of < 0.001. A follow up language test and intelligence quotient level score were done and showed a highly significant improvement with p value of (0.001 and 0.009) respectively. Conclusion Epileptiform activities with or without epilepsy in children may alter normal language function. Treatment of these epileptogenic activity affect improvement of this language dysfunction. Trial registration: ClinicalTrials.gov I.D: NCT05487521.

Endovascular thrombectomy for ischemic stroke with large infarct, short- and long-term outcomes: a meta-analysis of 6 randomised control trials.

Endovascular Thrombectomy (EVT) as first-line treatment of patients with large core ischemic infarct is a subject of debate. A systematic literature search was conducted in four electronic databases for randomized control trials (RCTs) comparing EVT to best medical treatment (BMT) for large core infarcts (ASPECTS ≤ 5). Relevant studies were added after screening for titles, abstracts, and complete text. Meta-analysis was performed. The continuous outcomes were analyzed using the standardized mean difference (SMD) and 95% CI, while the binary outcomes were analyzed using the risk ratio (RR) and 95% confidence interval (CI). A funnel plot was used to visually evaluate publication bias, and if feasible, Egger's test was used to validate. We included 1918 patients from six RCTs that compared EVT plus BMT and BMT alone in patients with large core infarct due to large vessel occlusion in the anterior circulation. There were 946 patients in the EVT group and 972 patients in the BMT group. The one-year outcomes are available for 314 patients in the EVT group and 292 patents in the BMT group from two RCTs. EVT group had statistically significant higher rate of 90-day mRS 0-1 (RR = 3.1, P-value < 0.0001), mRS 0-2 (RR = 2.64, P-value < 0.0001), mRS 0-3 (RR = 1.80, P-value < 0.0001), lower 90-day mean mRS score (SMD = -0.29, P-value < 0.0001), lower 90-day mortality rate (RR = 0.85, P-value = 0.015), and greater early neurological improvement (RR = 2.16, P-value < 0.00001) compared to the BMT group. However, the rates of symptomatic intracerebral hemorrhage (sICH) (RR = 1.76, P-value = 0.01) and any ICH (RR = 2.18, P-value < 0.00001) were higher in EVT group. Our finding showed that EVT plus BMT led to in an absolute improvement of 5%, 12%, and 16% in 90-day mRS 0-1, 0-2, and 0-3, respectively. In addition, patients in EVT plus BMT group had a 3% increased probability of experiencing sICH and were 32% more susceptible to any ICH. Moreover, the one-year mRS 0-2 (RR = 2.16, P-value < 0.00001) and mRS 0-3 (RR = 1.80, P-value < 0.0001) was significantly favor the EVT plus BMT over BMT alone. Although, the one-year mortality rate was not significantly differed between two groups (RR = 0.91, P-value = 0.31). There was no statistically significant difference observed between the EVT plus BMT group and the BMT group concerning new stroke, decompressive craniectomy, and serious adverse events. Combined data from six RCTs shows that EVT plus BMT provides significantly better short- and long-term functional outcomes with minimal increase in symptomatic hemorrhage over BMT in patient with large core infarcts.

Romosozumab versus parathyroid hormone receptor agonists: which osteoanabolic to choose and when?

Osteoanabolic agents are used as a first line treatment in patients at high fracture risk. The PTH receptor 1 (PTH1R) agonists teriparatide (TPTD) and abaloparatide (ABL) increase bone formation, bone mineral density (BMD), and bone strength by activating PTH receptors on osteoblasts. Romosozumab (ROMO), a humanized monoclonal antibody against sclerostin, dramatically but transiently stimulates bone formation and persistently reduces bone resorption. Osteoanabolic agents increase BMD and bone strength while being more effective than antiresorptives in reducing fracture risk in postmenopausal women. However, direct comparisons of the antifracture benefits of osteoanabolic therapies are limited. In a direct comparison of TPTD and ABL, the latter resulted in greater BMD increases at the hip. While no differences in vertebral or non-vertebral fracture risk were observed between the two drugs, ABL led to a greater reduction of major osteoporotic fractures. Adverse event profiles were similar between the two agents except for hypercalcemia, which occurred more often with TPTD. No direct comparisons of fracture risk reduction between ROMO and the PTH1R agonists exist. Individual studies have shown greater increases in BMD and bone strength with ROMO compared with TPTD in treatment-naive women and in women previously treated with bisphosphonates. Some safety aspects, such as a history of tumor precluding the use of PTH1R agonists, and a history of major cardiovascular events precluding the use of ROMO, should also be considered when choosing between these agents. Finally, convenience of administration, reimbursement by national health systems and length of clinical experience may influence patient choice.

Life-threatening amiodarone-induced thyrotoxicosis – Personalized approach to radical treatment

ObjectiveAmiodarone is an iodine-rich molecule and an effective antiarrhythmic drug. It is a first-line treatment for patients with life-threatening ventricular arrhythmias and for prevention in patients at high risk. The use of amiodarone may cause serious adverse effects such as pharmacotherapy-resistant, life-threatening amiodarone-induced thyrotoxicosis (AIT)leading to rapid deterioration of the patient's condition.According to the European Thyroid Association (ETA) guidelines, emergency thyroidectomy is the first-line treatment option in these cases. ; however, is not always feasible in the clinical setting due to the high anesthetic risk.We aimed to assess the clinical course and results of urgent thyroidectomy and 131-I therapy in patients with severe AIT with worsening of cardiac status. MethodsRetrospective analysis of the clinical course and outcomes of life-threatening AIT refractory to pharmacotherapy in patients hospitalized at a tertiary endocrinology center between 2014 and 2022. ResultsAn electronic database search identified 75 patients hospitalized for severe AIT. At the time of AIT diagnosis, median Thyroid-stimulating hormone (TSH) concentration was 0.001 mIU/L (range 0.001–0.35), fT4 63.2 pmol/L (range 9.0 - >100), and fT3 10.2 pmol/L (range 3.8–49.3). All patients received optimal conservative treatment. Among them, 20 required urgent radical therapy due to worsening arrhythmias and/or AIT-related heart failure. In this group, 6 patients died before any radical treatment was applied, 6 underwent total thyroidectomy, while 8 patients were successfully treated with 131-I (in 6 cases after rhTSH stimulation). The median dose of 131-I used for the therapy was 784MBq (range 627–860). The decision to treat with 131-I despite low but detectable 131-I uptake (median value 6 %) was made in cases of significant contraindications to anesthesia due to refractory ventricular arrhythmias, exacerbation of severe heart failure unresponsive to cardiac treatment, myocardial infarction during AIT course, massive pulmonary embolism. ConclusionThe decision regarding the optimal time and type of radical treatment of AIT refractory to pharmacotherapy is critical for patients management and should not be delayed. Urgent therapy with 131-I may be an effective therapeutic option in patients who are unsuitable for thyroidectomy due to the high risk of anesthesia.

Serplulimab combined with gemcitabine, nab-paclitaxel and stereotactic body radiotherapy as the first-line treatment for patients with metastatic pancreatic adenocarcinoma in China: a multicentre, single-arm, phase II trial (ICSBR) protocol

IntroductionPatients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours,...

First-line treatment for femoroacetabular impingement syndrome and hip-related quality of life: study protocol for a multicentre randomised controlled trial comparing a 6-month supervised strength exercise intervention to usual care (the Better Hip Trial)

IntroductionFemoroacetabular impingement syndrome (FAIS) is a motion-related and position-related clinical condition of the hip associated with pain, reduced physical function and hip-related quality of life (QoL). Interestingly, higher maximal muscle...

Renin-angiotensin system inhibitor prescriptions in Chinese hospitalized chronic kidney disease patients

BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients. AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China. METHODS It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription. RESULTS A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age &lt; 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions. CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.

Subcutaneous amivantamab and lazertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Results from the phase 2 PALOMA-2 study.

LBA8612 Background: Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, is approved as an intravenous (IV) formulation. IV ami + lazertinib (laz), a 3rd-generation EGFR TKI, demonstrated superior progression-free survival (PFS) in patients (pts) with treatment-naïve, advanced EGFR-mutated NSCLC vs osimertinib (Cho Ann Oncol 2023). Subcutaneous (SC) ami substantially reduced infusion-related reactions (16% vs 67%) and administration time (≤7 mins vs 2–4 hours) vs historical IV experience (Minchom JCO 2023). PALOMA-2 (NCT05498428) evaluated the efficacy, safety, and pharmacokinetics (PK) of first-line SC ami+laz. Methods: Cohorts 1 and 6 enrolled pts with treatment-naïve, EGFR Ex19del or L858R-mutated advanced NSCLC. Prophylactic anticoagulation for the first 4 months (mo) of treatment was recommended in cohort 1 and mandatory in cohort 6. SC ami was administered by manual injection in the abdomen at 1600 mg (≥80 kg: 2240 mg) weekly for the first 4 weeks and every 2 weeks thereafter. Laz was dosed orally at 240 mg daily. The primary endpoint was objective response rate (ORR) as assessed by the investigator per RECIST v1.1. Results: As of 6 Jan 2024, 68 and 58 pts were enrolled in cohorts 1 and 6, respectively. Overall, median age was 59 years, 60% were female, and 68% Asian. The median follow-up was 10 mo for cohort 1 and 6 mo for cohort 6. ORR (confirmed responses) in cohort 1 was 68% (95% CI, 55–79) by investigator and 72% (95% CI, 60–82) by independent central review. ORR in cohort 6 was 64% (95% CI, 49–78) and 73% (95% CI, 58–85), respectively. At data cutoff, 40/46 responders in cohort 1 and 29/29 responders in cohort 6 were receiving ongoing treatment. Best overall response rates (includes unconfirmed responses) were 81% (95% CI, 70–89) for cohort 1 and 76% (95% CI, 61–87) for cohort 6. Median time to response was 2 mo (range, 1.4–5.3). Median duration of response, PFS, and overall survival were not estimable. Administration-related reactions (ARRs) were reported in 13 (19%) pts in cohort 1 and 6 (11%) pts in cohort 6, all grade 1–2. EGFR- and MET-related AEs were primarily grade 1–2. Total of 71% of pts in cohort 1 and 100% in cohort 6 received prophylactic anticoagulation. Venous thromboembolic events (VTE) were reported in 18% and 7% of pts in cohorts 1 and 6, respectively. There were no dose reductions or discontinuations due to VTE. Rate of bleeding was 2% among pts receiving anticoagulation. Mean ami concentrations on cycle 2 day 1 were 328 µg/mL (n=49) in cohort 1 and 371 µg/mL (n=41) in cohort 6, consistent with historic IV levels. Conclusions: SC ami+laz showed a response rate similar to historic IV ami+laz in first-line EGFR-mutated NSCLC, with an improved safety profile that included significantly lower ARR rates. Further, prophylactic anticoagulation can be safely implemented and reduced incidence of VTE. Clinical trial information: NCT05498428 .

Retrospective registry of patients with locally advanced/metastatic HR+/HER2- breast cancer treated in clinical practice in Andalusia.

Limited data are available regarding the real-world effectiveness and safety of Cyclin Dependent Kinase 4/6 inhibitor (CDK4/6i) (palbociclib/ribociclib) just as a first-line treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2‒) metastatic breast cancer (MBC). To assess whether clinical or demographic characteristics limit access to first-line CDK4/6i treatment in clinical practice in the Autonomous Community of Andalusia (Spain) between November 2017 and April 2020. In addition, effectiveness will be described in an exploratory analysis. Physicians from 12 centers participated in selecting demographic and clinical characteristics, treatment, and outcome data from women with HR + /HER2- MBC treated with or without CDK4/6i in addition to hormonal in the first-line setting, in a 3:1 proportion. Kaplan-Meier analysis estimated progression-free rates (PFRs) and survival rates (SRs). A total of 212 patients were included, of whom 175 (82.5%) were in the CDK4/6i treatment group and 37 (17.5%) were in the non-CDK4/6i treatment group (control group). Patients in the CDK 4/6i treatment group were younger (p = 0.0011), the biopsies of the metastatic site at the moment of the relapse were most commonly performed (p = 0.0454), and had multiple metastatic sites (p = 0.0025). The clinical benefit rate (CBR) was 82.3% in the CDK4/6i group and 67.8% in the control group. Median time to a progression event or death (PFS) was 20.4months (95%CI 15.6-28) in the CDK4/6i group and 12.1months (95%CI 7.9-not reached) in the control group. Younger patients, biopsies of metastatic disease and with multiple metastatic sites were more frequently treated with CDK4/6i in our daily clinical practice.

Cure can be Achieved by Conversion to Microwave Ablation following Atezolizumab-Bevacizumab Therapy in Unresectable Hepatocellular Carcinoma.

Atezolizumab/bevacizumab is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC) and may facilitate curative conversion through resection and locoregional therapies. However, there have been very few reports on curative conversion using microwave ablation (MWA). This study aimed to determine the curative conversion rate with MWA using atezolizumab-bevacizumab as the first-line treatment in patients with uHCC, and to compare the characteristics and survival of patients with and without curative conversion. Consecutive patients with uHCC who were started on atezolizumab-bevacizumab from May 2021 and December 2023 in a single tertiary center were included. Objective response (ORR) and disease control rate (DCR) were based on the RECIST 1.1 and mRECIST criteria. Twenty consecutive patients with uHCC (60% advanced-stage) were included, 90% exceeding the up-to-7 criteria. The ORR and DCR were 35% and 60%, and 35% and 55% using RECIST and mRECIST, respectively. Five (25%) patients underwent successful curative conversion with MWA (4 advanced and 1 intermediate stage) despite a median HCC size of 6.1 (range: 2.4-7.3) cm. Two of these patients were tumor and drug-free 132-133 weeks from the 1st atezolizumab-bevacizumab dose. Patients who underwent curative conversion had significantly longer survival than those who did not. (p=0.024) Other factors associated with survival were male sex, Child-Pugh class A, and an objective response. Despite the relatively large tumor size, successful curative conversion with MWA was achieved with first-line atezolizumab-bevacizumab in uHCC. However, data from prospective multicenter trials are required to determine whether this strategy is universally applicable.

Efficacy and safety of arterial FOLFOX chemotherapy plus anti-PD-(L)1 immunotherapy as first-line treatment for unresectable intrahepatic cholangiocarcinoma: A propensity score matched analysis.

e16189 Background: This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus anti-programmed death (ligand)-1 [PD-(L)1] immunotherapy compared to systemic chemotherapy (SCT) plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma (uICC). Methods: In this retrospective study, unresectable treatment-naive ICC patients who were treated with HAIC plus anti-PD-(L)1 immunotherapy [HAIC+αPD-(L)1] or SCT plus anti-PD-(L)1 immunotherapy [SCT+αPD-(L)1] were included. The clinical characteristics, therapeutic outcomes and adverse events (AEs) of patients between the two groups were compared. The propensity score matching (PSM) was performed to minimize biases between groups. Results: From January 2019 to January 2023, a total of 182 patients were enrolled, including 147 patients in HAIC+αPD-(L)1 group and 35 patients in SCT+αPD-(L)1 group. After PSM, 61 and 26 patients were included in the HAIC+αPD-(L)1 and SCT+αPD-(L)1 groups, respectively. The HAIC+αPD-(L)1 group showed longer median overall survival (OS) and progression free survival (PFS) than the SCT+αPD-(L)1 group (OS: 14.5 vs 10.5 months, P = 0.019; PFS: 6.4 vs 10.1 months, P = 0.020). The disease control rate of HAIC+αPD-(L)1 group were higher than those of SCT+αPD-(L)1 group (91.8% vs 69.2%, P = 0.007). The overall incidence of adverse events (AEs) was comparable between the two groups, but the HAIC+αPD-(L)1 group showed a lower incidence of grade 3~4 AEs related to anemia, weight loss and fatigue. Conclusions: HAIC plus anti-PD-(L)1 immunotherapy had acceptable toxic effects and might improve outcomes compared to SCT plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with uICC.

A multicenter, single-arm, open-label phase II study to evaluate the efficacy and safety of YH003 in combination with pembrolizumab and nab-paclitaxel in the first-line treatment of patients with unresectable/metastatic mucosal melanoma.

e21520 Background: Mucosal melanoma therapy remains a formidable challenge especially in Asia. Although several therapies are available for skin type of melanoma, the efficacy of mucosal melanoma is not satisfactory. YH003, a humanized agonistic anti-CD40 monoclonal antibody specifically recognizes and agonizes CD40 to enhance immune responses, has demonstrated good safety and promising antitumor activity in Phase I clinical studies in patient with ocular melanoma. Here, we report the results of the phase II study of YH003 in combination with pembrolizumab and nab-paclitaxel in the first-line treatment of patients with unresectable/metastatic mucosal melanoma. Methods: Patients with unresectable/metastatic mucosal melanoma were enrolled and received 0.3 mg/kg YH003, 200 mg pembrolizumab and 200 mg/m2 of nab-paclitaxel iv, every 21 days. The treatment continued for 12 months if subject was deriving an ongoing clinic benefit. The primary endpoint was overall Response Rate (ORR) by investigator’s assessment per RECIST 1.1. Results: A total of 20 patients were enrolled and had at least 1 evaluable post-treatment tumor assessment, the unconfirmed ORR was observed in 7 patients (35.0%), with 7 partial responses (PR). 7 patients (35.0%) had stable disease (SD), and the Disease Control Rate (DCR) was 70.0%. The mOS was not reached, mPFS was 4.11 months. The grade 3 or above TEAE that occurred in the 20 patients were 30.0% (6/20). There is no significant safety signal from the study. Conclusions: The results of the phase II study have shown that YH003 in combination with pembrolizumab and nab-paclitaxel, as 1L treatment in patients with unresectable/metastatic mucosal melanoma have promising antitumor activity and response durability and well tolerated. Clinical trial information: NCT05420324 .

Efficacy and safety of arterial FOLFOX chemotherapy plus anti-PD-(L)1 immunotherapy as first-line treatment for unresectable intrahepatic cholangiocarcinoma: A propensity score matched analysis.

e16189 Background: This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus anti-programmed death (ligand)-1 [PD-(L)1] immunotherapy compared to systemic chemotherapy (SCT) plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma (uICC). Methods: In this retrospective study, unresectable treatment-naive ICC patients who were treated with HAIC plus anti-PD-(L)1 immunotherapy [HAIC+αPD-(L)1] or SCT plus anti-PD-(L)1 immunotherapy [SCT+αPD-(L)1] were included. The clinical characteristics, therapeutic outcomes and adverse events (AEs) of patients between the two groups were compared. The propensity score matching (PSM) was performed to minimize biases between groups. Results: From January 2019 to January 2023, a total of 182 patients were enrolled, including 147 patients in HAIC+αPD-(L)1 group and 35 patients in SCT+αPD-(L)1 group. After PSM, 61 and 26 patients were included in the HAIC+αPD-(L)1 and SCT+αPD-(L)1 groups, respectively. The HAIC+αPD-(L)1 group showed longer median overall survival (OS) and progression free survival (PFS) than the SCT+αPD-(L)1 group (OS: 14.5 vs 10.5 months, P = 0.019; PFS: 6.4 vs 10.1 months, P = 0.020). The disease control rate of HAIC+αPD-(L)1 group were higher than those of SCT+αPD-(L)1 group (91.8% vs 69.2%, P = 0.007). The overall incidence of adverse events (AEs) was comparable between the two groups, but the HAIC+αPD-(L)1 group showed a lower incidence of grade 3~4 AEs related to anemia, weight loss and fatigue. Conclusions: HAIC plus anti-PD-(L)1 immunotherapy had acceptable toxic effects and might improve outcomes compared to SCT plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with uICC.