First-line Treatment Option Research Articles

Comparative efficacy of cetuximab combined with FOLFOX or CAPEOX in first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer: a multicenter case-control study.

FOLFOX combined with cetuximab is a recommended first-line treatment regimen for RAS/BRAF wild-type metastatic colorectal cancer (mCRC). CAPEOX combined with cetuximab differs from the FOLFOX regimen by using oral capecitabine instead of continuous infusion of fluorouracil, offering greater convenience and cost-effectiveness with higher patient acceptance. However, the comparative efficacy of these two regimens remains debatable, necessitating further evidence to explore any differences in their efficacy. This study collected medical records of mCRC patients who were treated with CAPEOX or FOLFOX combined with cetuximab from 1 October 2021 to 16 October 2023 at Harbin Medical University Cancer Hospital and the First Hospital of Shanxi Medical University. Eligible patients were selected based on inclusion criteria and followed up through the hospital's follow-up system and telephone interviews. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were used to assess patients' progression-free survival (PFS) and overall survival (OS). A total of 71 eligible patients were enrolled in this study; 43 patients received CAPEOX combined with cetuximab (Group A, n = 43), and 28 patients received FOLFOX combined with cetuximab (Group B, n = 28). The two groups achieved similar median PFS (mPFS) and median OS (mOS), with mPFS of 18 months and 12 months, respectively (P = 0.23), and mOS of 33 months and 20 months, respectively (P = 0.21), with no statistically significant differences. The results of this study demonstrated that CAPEOX combined with cetuximab is an equally viable option for first-line treatment of RAS/BRAF wild-type mCRC as FOLFOX combined with cetuximab.

Updated efficacy and subgroup analysis of first-line serplulimab plus bevacizumab and XELOX versus placebo plus bevacizumab and XELOX in metastatic colorectal cancer: A phase 2/3 study.

170 Background: This is a randomized, double-blind, multicenter phase 2/3 study comparing the efficacy and safety of serplulimab (a novel anti-PD-1 antibody) plus bevacizumab and XELOX chemotherapy vs. placebo plus bevacizumab and XELOX as first-line treatment for metastatic colorectal cancer (mCRC). Our previous presentation at the 2024 ASCO Meeting showed the progression-free survival results. Here we present the updated efficacy and safety findings together with subgroup analysis results after a median follow-up of 31.0 months. Methods: A total of 114 patients with mCRC and no prior systemic therapy were randomized 1:1 (serplulimab arm, n = 57; placebo arm, n = 57) to receive intravenous (IV) serplulimab (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (IV oxaliplatin [130 mg/m 2 ] and oral capecitabine [1000 mg/m 2 ]) (group A) or placebo plus bevacizumab and XELOX (group B) once every 3 weeks. Stratification factors were PD-L1 expression level, ECOG PS score, and primary tumor site. The primary endpoint was independent radiological review committee (IRRC)-assessed PFS per RECIST 1.1. Secondary endpoints included other efficacy endpoints, safety, pharmacokinetics, biomarker explorations, and quality-of-life assessments. Results: In the phase 2 part, by the data cutoff of June 30, 2024, sustained improvements in PFS (16.6 vs. 10.7 months, stratified HR 0.66, 95% CI 0.37–1.19) and DOR (17.7 vs. 11.3 months, stratified HR 0.45, 95% CI 0.20–0.98) were observed for patients in group A compared to group B in the modified intent-to-treat population (n = 112; two patients in group A did not receive any intended study treatment). 32/55 (58.2%) patients in group A and 35/57 (61.4%) in group B have died. Median overall survival (OS) was 25.6 months in group A and 21.2 months in group B (stratified HR 0.86, 95% CI 0.53–1.42). A trend of PFS and OS benefits was similarly observed for the patients with a microsatellite stable (MSS) status (PFS: 16.8 vs. 10.1 months, stratified HR 0.65, 95% CI 0.33–1.29; OS: 23.5 vs. 20.2 months, stratified HR 0.79, 95% CI 0.45–1.38). 39 (70.9%) patients in group A and 34 (59.6%) in group B had grade ≥3 treatment-related adverse events. Serplulimab/placebo-related serious TRAEs occurred in 13 (23.6%) patients in group A and 14 (24.6%) patients in group B. Conclusions: With a follow-up duration of 31.0 months, improved survival benefits demonstrated with the addition of serplulimab were maintained in the first-line treatment of mCRC patients including those with MSS status alongside a manageable safety profile. The phase 3 part of this study is currently ongoing to further evaluate serplulimab plus bevacizumab and XELOX as a first-line treatment option in mCRC. Clinical trial information: NCT04547166 .

A phase 2 study of amplitude-modulated radiofrequency electromagnetic fields (AM RF EMF) in metastatic pancreatic cancer.

TPS790 Background: Patients with advanced pancreatic adenocarcinoma (PDC) that progresses after first-line therapy face limited treatment options. Despite advances in systemic therapy, the prognosis for PDC is dismal, with a five-year overall survival (OS) of about 5% . Due to the high morbidity of this disease, there is a critical need for innovative treatments to improve patient outcomes. TheraBionic P1, a hand-held device, delivers tumor specific radio frequencies via a spoon-shaped antenna placed on the patient's tongue. The FDA and EMA have confirmed the safety of the device for amplitude-modulated electromagnetic field (AM-EMF) therapy. Improved efficacy outcomes were reported with AM RF EMF in other solid organ tumors including pancreatic cancer in preliminary studies. Preclinical and clinical evidence suggests that AM-EMF can inhibit tumor growth and was recently approved for use in hepatocellular cancer. The safety and clinical activity observed with AM RF EMF, paired with the unmet medical need for additional effective therapies in pancreatic cancer, provided a strong rationale for further clinical investigation. This protocol evaluates the efficacy and tolerability of AM RF EMF in combination with standard of care frontline therapy, gemcitabine and nab-paclitaxel for metastatic PDC. Methods: This is an ongoing, single-center, Phase II, non-randomized study using a Simon two-stage minimax design to assess the efficacy of AM-EMF in combination with gemcitabine/nab-paclitaxel as a first-line treatment in metastatic pancreatic cancer. Gemcitabine and nab-paclitaxel are administered per standard care. AM RF EMF are delivered to patients with a spoon-shaped applicator placed on the tongue three daily 60-minute treatments. Patients will be assessed for response every 8 weeks. Treatment is continued until progression or toxicity. The primary objective of this study is to evaluate the efficacy of the combination of nab-paclitaxel, gemcitabine, and AM RF EMF in improving 6-month overall survival rates in patients with metastatic PDC. Secondary objectives evaluate the safety, tolerability, profession free survival, objective response rate and disease control rate. Exploratory objectives evaluate change in CA19-9 and quality of life using FACT-General (FACT-G) and determine any possible correlation with clinical outcomes. Key eligibility includes treatment-naïve, histologically confirmed metastatic PC, age eighteen years old or greater, ECOG 0-1, and optimal organ function. Clinical trial information: NCT05776524 .

Total cost of care of immune-oncology treatments for unresectable hepatocellular carcinoma: A Singapore healthcare perspective analysis.

642 Background: Tremelimumab + durvalumab (STRIDE) and atezolizumab + bevacizumab are recommended first-line immune-oncology treatment options for unresectable hepatocellular carcinoma (uHCC). This study aimed to quantify the total economic burden to the Singapore healthcare system of treating patients with uHCC using STRIDE versus atezolizumab + bevacizumab. Methods: A model was developed to estimate the total cost of care of using STRIDE or atezolizumab + bevacizumab, which followed patients with uHCC eligible for first-line systemic therapy, considering direct medical costs. Costs considered in the model included treatment acquisition and administration, endoscopy, healthcare resource use, and cost for treating grade ≥3 treatment-emergent adverse events (TEAEs). Data on treatment regimens and TEAEs were taken from the HIMALAYA (STRIDE) and IMbrave150 (atezolizumab + bevacizumab) trials. Resource use rates were based on an average of 168 days treatment for both regimens. All costs were obtained from Singaporean sources. Results: The total cost of care for STRIDE and atezolizumab + bevacizumab was estimated at SGD$40,277 (USD$30,932) and SGD$43,605 (USD$33,487) per patient, respectively. This translates into an average cost savings of SGD$3,328 (USD$2,555]) per patient when treated with STRIDE compared to atezolizumab + bevacizumab. The main driver of cost savings was treatment acquisition and administration (-SGD$1,917 [-USD$1,472], -6%) though lower costs were also associated with resource use (-SGD$927 [-USD$712], -8%), endoscopy (-SGD$342 [-USD$263], -77%) and TEAE management (-SGD$141 [-USD$108], -74%). Assuming an incident population of 260 patients eligible for treatment, the total burden was estimated at SGD$10,489,604 (USD$8,055,696) when all patients were treated with STRIDE, and SGD$11,356,273 (USD$8,721,271) when treated with atezolizumab + bevacizumab (Table). The incremental cost offset to the health plan was SGD$866,669 (USD$665,575) when treated with STRIDE. Conclusions: This study suggests that STRIDE offers cost savings over atezolizumab + bevacizumab for uHCC treatment in the Singapore healthcare system. Additional real-world evidence studies are warranted to capture the long-term survival benefits and associated treatment costs. Annual cost of care based on 260 patients receiving first-line immune-oncology treatment. Category STRIDE Atezolizumab + Bevacizumab Incremental difference Endoscopy costs $26,358 $115,555 -$89,197 Resource Use costs* $2,607,000 $2,848,307 -$241,307 Adverse events costs $12,899 $49,716 -$36,817 Treatment acquisition and administration $7,843,347 $8,342,696 -$499,349 TOTAL $10,489,604 $11,356,273 -$866,669 All costs in SGD$. *Includes: physician visits; laboratory and radiological tests; and hospitalisation.

A phase two trial evaluating FOLFIRI plus aflibercept after failure of FOLFOXIRI plus bevacizumab in patients with unresectable metastatic colorectal cancer.

FOLFOXIRI plus bevacizumab (BEV) is an option for first-line treatment of metastatic colorectal cancer (mCRC). However, there is no consensus on the optimal treatment strategy when disease progresses. The EFFORT open-label, multicenter, single-arm phase II study investigated whether FOLFIRI plus aflibercept retains activity after progression of FOLFOXIRI plus BEV treatment. The patients with unresectable mCRC who failed first-line FOLFOXIRI plus BEV received FOLFIRI plus aflibercept. The primary endpoint was progression-free survival (PFS) in the full analysis set (FAS). Angiogenic biomarkers were measured before treatment initiation. From April 2019 to May 2021, 35 patients were enrolled and 34 were analysed in the FAS population (men, 18; median age, 63years [range: 32-78]). The primary tumor was left-sided in most cases (23/34), 23 patients were RAS mutant, 3 patients had BRAF V600E mutation and 27 patients had liver metastases. The primary end-point was met with a median PFS of 4.3months [80% confidence interval [CI] 3.7-5.1]. Median overall survival was 15.2months [95% CI 8.9-22.7]. Per RECIST, there were 1 complete response, 4 partial responses, 21 stable diseases and 8 disease progressions. Overall response rate was 14.7% [95% CI 5.0-31.1], and disease control rate was 76.5% [95% CI 58.8-89.3]. Responses were more common in patients with high VEGF-C, low VEGF-D and low PlGF levels before treatment. FOLFIRI plus aflibercept, administered after failure of FOLFOXIRI plus BEV, is effective and has a manageable safety profile. This regimen may be a useful second-line treatment option for these patients.

Even With the CROWN Findings, There Remain Multiple First-Line Treatment Options for Patients With Advanced ALK–Positive NSCLC

Even With the CROWN Findings, There Remain Multiple First-Line Treatment Options for Patients With Advanced ALK–Positive NSCLC

Comparative efficacy and safety of first-line neoadjuvant therapy for early-stage non-small cell lung cancer based on immune checkpoint inhibitor therapy: a systematic review and network meta-analysis

IntroductionAlthough there are a number of neoadjuvant immunotherapy combinations that can be applied to the treatment of perioperative non-small cell lung cancer patients, the optimal treatment combination strategy has not yet been determined.MethodsWe searched PubMed, EMBASE, Cochrane Library, ClinicalTrials.go and randomised controlled trials (RCTs) from major international conferences for literature related to neoadjuvant immunotherapy combinations published as first-line treatment options for non-small cell lung cancer from the start of the library to 20 February 2024, and performed a systematic review and network meta-analysis.ResultsWe analyzed nine studies involving 3431 patients, including eight perioperative neoadjuvant immunotherapy combinations for non-small cell lung cancer. For patients without programmed death-ligand 1(PD-L1) selection, Toripalimab plus chemotherapy provided the best Pathological complete response (PCR) benefit (OR = 32.89,95% CI:7.88-137.32), best Major Pathological response (MPR) benefit (OR = 10.25, 95% CI: 5.81–18.10) and best Event-free survival (EFS) benefit (HR = 0.40,95% CI: 0.28–0.57). Nivolumab plus chemotherapy provided the best surgical resection rate (OR = 1.71, 95% CI:0.87–3.40) and pembrolizumab plus chemotherapy provided the best R0 surgical resection rate (OR = 2.20, 95% CI:1.28–3.79). In contrast, the combination of ipilimumab, nivolumab and chemotherapy, and the combination of toripalimab and chemotherapy were associated with the lowest incidence of adverse events of grade 3 or above during neoadjuvant therapy.ConclusionsOur findings suggest that: Toripalimab plus chemotherapy showed better neoadjuvant efficacy and may have an overall survival benefit, but also increased the incidence of serious adverse events during neoadjuvant therapy.

P-1676. Retrospective Evaluation of the Impact of Infectious Diseases Consultation on Prescribing Patterns and Clinical Outcomes among Patients with Gram-negative Bacteremia in the Community Hospital Setting

Abstract Background Gram-negative bloodstream infections (BSI) are concerning due to high mortality rates reporting up to 30%; however, infectious diseases (ID) consultation has been associated with reduced mortality. According to consensus statement recommendations, fluoroquinolones (FQ) or trimethoprim-sulfamethoxazole (TMP/SMZ) are first-line oral treatment options and high bioavailable beta-lactams (HBBL) are alternatives for the treatment of Gram-negative BSI. The objective of this study is to evaluate differences in oral antibiotic prescribing patterns and outcomes between ID and non-ID providers among patients with Enterobacterales BSI in a community hospital setting. Methods This is a multi-centered, retrospective cohort. Adult patients who received treatment for confirmed Enterobacterales BSI between January 1, 2022 and June 30, 2023 were included. Patients who completed treatment with only IV antibiotics, were greater than 89 years of age, elected palliative or hospice care before completion of treatment, died prior to receiving oral antibiotics, or with polymicrobial blood cultures were excluded. The primary outcome was the proportion of patients ordered FQ, TMP/SMZ, HBBL, or low-moderate bioavailable beta-lactam (LBBL) as oral stepdown. Secondary outcomes included length of stay, IV, oral, and total length of therapy (LOT), 30-day readmission, Clostridioides difficile infection (CDI), and all-cause mortality. The primary outcome was analyzed using a chi-square test with post hoc Bonferroni adjusted z tests to determine specific categorical differences. Results In the ID consult group (n=95) 72.6% of patients received a FQ, 6.3% TMP/SMZ, 16.8% HBBL, and 4.2% LBBL whereas in the non-ID consult group (n=77) 50.6% received a FQ, 5.2% TMP/SMZ, 39% HBBL, and 5.2% LBBL (p=0.009; Bonferroni z test p< 0.0125 for FQ and HBBL). Secondary outcomes did not differ significantly between the two groups. Conclusion FQ were more likely to be prescribed for oral stepdown in the ID consult group whereas HBBL were more likely to be prescribed in the non-ID consult group. Overall, among either group rates of prescribing were low for both TMP/SMZ and LBBL. Disclosures All Authors: No reported disclosures

Comparing the Efficacy of Combined Intralesional Triamcinolone Acetonide With Topical Calcipotriol Versus Intralesional Triamcinolone Acetonide Monotherapy in Scalp and Beard Alopecia Areata: Results From a Randomized Single-Blinded Clinical Trial.

Intralesional (IL) steroids are the first-line treatment option for localized alopecia areata (AA). The present study aimed to compare the efficacy of topical calcipotriol with IL triamcinolone acetonide versus IL triamcinolone acetonide alone in AA. This randomized single-blinded clinical trial was conducted in a dermatology outpatient department. Both groups A and B received IL triamcinolone acetonide injections every 4 weeks for 12 weeks. Group A also received twice-daily topical calcipotriol. Follow-up was done every 4 weeks till 12 weeks. The primary outcome parameter was hair density assessment using a hair regrowth scale (RGS). Other parameters were the presence or absence of poor clinical response (less than 50% hair density), regrowth patterns, dermoscopy features, and adverse effects. Seventy-three (179 patches) patients completed the study. RGS and patches with more than 50% terminal hair regrowth significantly improved in both the groups beginning in the fourth week and going forward (P-value: .001, .001). The two treatment groups exhibited no statistically significant difference in terminal hair density (P values: .930, .616, .178). However, subgroup analysis showed a statistically significant difference in scalp patches of group A compared to group B in the 12th week of the study (P = .018) but not in beard patches (P-value: .527). Group A exhibited more irritation with a reduced incidence of atrophy. The addition of topical calcipotriol to IL steroid showed increased efficacy in scalp patches of AA but not in beard patches. Also, the incidence of atrophy was lower in the combination group.

CXCR4 promotes tumor stemness maintenance and CDK4/6 inhibitors resistance in ER-positive breast cancer

BackgroundCDK4/6 inhibitors have significantly improved the survival of patients with HR-positive/HER2-negative breast cancer, becoming a first-line treatment option. However, the development of resistance to these inhibitors is inevitable. To address this challenge, novel strategies are required to overcome resistance, necessitating a deeper understanding of its mechanisms. Recent research has identified several dysregulated genes in CDK4/6 inhibitors-resistant breast cancer, but the underlying mechanism is complex due to tumor heterogeneity and warrants further investigation.MethodsRNA sequencing and KEGG pathway analysis was carried out to identify the mainly dysregulated genes in CDK4/6 inhibitors-resistant breast cancer cells. The effects of CXCR4 knockdown and overexpression via siRNAs and plasmids transfection were examined by mammosphere formation, RT-qPCR, flow cytometry, MTT and colony formation assays. The regulation mechanisms were analyzed by RT-qPCR, western blotting and immunofluorescence experiments. Mouse xenografts were used to analyze the role of CXCR4 in regulation palbociclib sensitivity in vivo. Additionally, we collected the clinical samples and performed immunohistochemistry to analyze the clinical significance of CXCR4.ResultsIn our study, we focused on cancer stem cells, a critical contributor to cancer metastasis and therapy resistance, and detected an upregulation of stemness in our established palbociclib-resistant ER-positive breast cancer cells. Additionally, our research pinpointed CXCR4 as a pivotal gene responsible for maintaining cancer stemness and promoting palbociclib resistance. Mechanistically, CXCR4 activates the WNT5A/β-catenin signaling pathway by enhancing the expression of WNT5A and β-catenin, facilitating the nuclear translocation of β-catenin protein. Targeting CXCR4 using siRNAs or small molecular inhibitors effectively reduces cancer stemness and reverses palbociclib resistance both in vitro and in vivo. Clinical sample analysis further underscores the overactivation of the CXCR4/WNT5A/β-catenin axis in palbociclib-resistant breast cancer, suggesting CXCR4 as a potential biomarker for predicting resistance to CDK4/6 inhibitors.ConclusionsCollectively, our study demonstrates that CXCR4 overexpression plays a vital role in maintaining breast cancer stemness and promoting resistance to CDK4/6 inhibitors through the activation of the WNT5A/β-catenin pathway. Targeting CXCR4 may offer a promising therapeutic approach for advanced CDK4/6 inhibitor-resistant ER-positive breast cancer.

Very Early Health Technology Assessment for Potential Predictive Biomarkers in the Treatment of Advanced Non-Small Cell Lung Cancer.

Immune checkpoint inhibitor (ICI)-containing treatment is currently prescribed as first-line treatment for all patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, only 30-45% of patients show no progression within 12 months after treatment start. Various biomarkers are being studied to save costly and potentially harmful treatment in non-responders. We evaluated the cost-effectiveness of implementing a hypothetical predictive biomarker for ICI-containing treatment response compared with standard of care (e.g., no implemented biomarker) for pembrolizumab-containing treatment in patients with advanced NSCLC in the Netherlands. Standard-of-care-based and predictive-biomarker-based strategies were compared using Markov models for three first-line pembrolizumab-containing treatments depending on a patient's tumor programmed cell death ligand-1 (PD-L1) expression and histology. A Dutch healthcare system perspective was adopted. Assuming a receiver operating characteristic-area under the curve of 1.0 in identifying responders, alternative treatments were offered for non-responders in the predictive-biomarker-based strategy. Parameters and assumptions were based on real-world data from surveys, literature using a targeted search, expert opinion, and registries. Outcomes included differences in costs, survival (life years (LYs)), and survival corrected for health-related quality of life (QoL) quality-adjusted life-years (QALYs) between the predictive-biomarker- and standard-of-care-based strategy. Implementing a predictive biomarker in pembrolizumab-carboplatin-paclitaxel treatment led to a mean survival reduction of 24 days (- 0.067 LYs) (18 days corrected for QoL (- 0.049 QALYs)), with cost savings of €22,606 compared with standard of care. Pembrolizumab monotherapy and pembrolizumab-pemetrexed-platinum treatments showed survival reductions of 4.5 and 3.9 months, respectively (3.6 and 2.8 months corrected for QoL), with cost savings of €24,345 and €28,456. Sensitivity analyses confirmed consistent cost savings and survival reductions. Survival losses were mainly observed due to the lower survival rates associated with the alternative first-line treatment options available for non-responders in the predictive-biomarker-based strategy within each pembrolizumab-containing treatment regimen. Pembrolizumab-carboplatin-paclitaxel treatment also showed survival gains under certain conditions related to QoL and survival estimates. Our study highlights the importance of careful de-implementation of ICI-treatments in advanced NSCLC, balancing costs reductions and side effects without comprising survival. In the pembrolizumab-carboplatin-paclitaxel treatment regimen, the survival loss could be considered negligible. Future research should define acceptable tradeoffs and thresholds for de-implementation, considering factors such as survival of alternative treatments and responder classification to guide predictive biomarker implementation and optimize health resource allocation.

Impact of Membranous Nectin-4 on Outcomes of Platinum-Based Chemotherapy in Metastatic Urothelial Carcinoma

Background: Platinum-based chemotherapy (Plt-ChT) remains a cornerstone treatment for metastatic urothelial carcinoma (mUC). The nectin-4-targeting antibody–drug conjugate enfortumab vedotin (EV), in combination with immune checkpoint inhibitors, has expanded first-line treatment options. However, biomarkers to guide treatment selection are lacking. Membranous nectin-4 (mNectin-4) expression, a potential marker of EV efficacy, has not been fully explored in the context of Plt-ChT. Methods: We retrospectively analyzed 96 patients with mUC treated with first-line gemcitabine plus cisplatin or carboplatin (GC/GCarbo) and classified mNectin-4 expression using immunohistochemical staining as either high (histochemical score (H-score): 100–300, mNectin-4High) or low (H-score: 0–99, mNectin-4Low). Results: Among these patients, 54.1% exhibited mNectin-4High tumors, which were associated with bladder-origin tumors, a pure urothelial carcinoma histology, de novo presentation, and lymph node-only metastasis. The mNectin-4High subgroup showed a non-significant trend toward better outcomes, including response rate (46.1% vs. 36.3%; p = 0.32), median progression-free survival (7.0 months vs. 4.0 months; adjusted p = 0.06), and median overall survival (20.0 months vs. 8.8 months; adjusted p = 0.06), compared with the mNectin-4Low subgroup. The subgroup analysis revealed that the favorable outcomes for mNectin-4High tumors were predominantly observed in the GC cohort, which was not evident in the GCarbo cohort. Conclusions: Our study suggests a non-significant trend toward improved outcomes with first-line Plt-ChT in patients with mNectin-4High tumors, particularly with the GC regimen. Larger prospective studies are warranted to validate mNectin-4 as a potential predictive biomarker for mUC treatment.

P0811 Comparative efficacy of vedolizumab and infliximab in patients with moderate-to-severe ulcerative colitis: a multicenter real world cohort study

Abstract Background Vedolizumab (VDZ) and infliximab (IFX) are both recognized as first-line treatment options for moderate to severe ulcerative colitis (UC). However, there is a paucity of comparative studies examining their real-world efficacy. Methods Patients with moderate to severe UC were consecutively enrolled from 11 centers. Efficacy were evaluated after 14 and 52 weeks. Logistic regression was conducted to identify independent risk factors for clinical remission. Results A total of 235 patients were enrolled, of which 154 received VDZ treatment and 81 received IFX treatment. 154 (65.5%) were male, with a median age of 40 (32, 49) years, a median disease duration of 7.0 (2.8, 11.9) years. The median baseline Mayo score was 9 (7, 11), and the median baseline partial Mayo score was 6 (4, 8). 16 patients (6.8%) had perianal lesions, and 41 patients (17.4%) had extraintestinal manifestations. At week 14, patients treated with IFX had higher clinical response rate (84.6% vs 66.2%, p = 0.003) but lower endoscopic remission rate (14.5% vs 34.3%, p = 0.003) compared to those treated with VDZ. There were no statistical difference in clinical remission rate between the two groups (39.7% vs 44.8%, p = 0.462). At week 52, there were no statistically difference in the modified Mayo score, partial Mayo score, clinical response rate, clinical remission rate, and endoscopic remission rate between IFX treatment group and VDZ treatment group (p>0.05). Multivariate regression analysis demonstrated that baseline disease extent was a predictor of clinical remission at week 14 of VDZ treatment (OR = 3.55, 95% CI 1.39–9.06, p = 0.008). Conclusion IFX group received higher clinical response rate but not endoscopic remission rate at week 14. The efficacy of IFX was comparable to VDZ at week 52. Disease extent was a predictor of clinical remission at 14 weeks with VDZ.

Cross-sectional study of treatment approaches of luminal HER2negative metastatic breast cancer in real practice in Moscow

Introduction: The systemic therapy of patients with metastatic luminal HER2‑negative breast cancer (mBC) in‑ cludes various options, which can be fundamentally divided into endocrine therapy and chemotherapy. According to the Clinical Guidelines, both international and Russian, the “gold standard” of the 1st line therapy for patients with metastatic luminal HER2‑negative breast cancer (mBC) is a combination of cyclindependent kinase inhib‑ itors 4 / 6 (iCDK4 / 6) with endocrine therapy (ET). However, until recently we did not have complete data on the characteristics of the Russian population of patients with luminal HER2‑breast cancer, their treatment options, and the results of this therapy.Aim: To analyze the patients’ profile and current treatment approaches for patients with luminal HER2 mBC in routine clinical practice in Moscow.Materials and methods: The study was performed as an observational, crosssectional and retrospective study. The data of 2,500 patients from medical institutions in Moscow who received systemic therapy for luminal HER2 mBC in AugustOctober 2021 were analyzed.Results: The largest number of patients received iCDK4 / 6 + ET in the first and second lines: 69.0 % and 52.0 %, respectively. In the first line, 54.6 % of patients received ribociclib, 43.1 % palbociclib and 2.3 % abemaciclib. In the second line, 50.6 % of patients received ribociclib, 47.8 % palbociclib and 1.6 % abemaciclib. As the pretreatment of patients increased, preference was given to other treatment methods, therefore the proportion of combined ET decreased to 34.0 % in the third line and 25.0 % in the fourth and subsequent lines.Conclusion: The data obtained indicate that the appointment of iCDK4 / 6 + ET is made in accordance with the Clinical Guidelines for the treatment of breast cancer of the Ministry of Health of the Russian Federation from 2021 and the preferred firstline treatment option for patients with luminal HER2 mBC in Moscow is combined endocrine therapy.

Percutaneous Balloon Pericardiotomy: A Safe and Effective Approach for Managing Recurrent Massive Pericardial Effusion.

Percutaneous balloon pericardiotomy (PBP) has emerged as a less invasive alternative to surgical interventions for recurrent severe pericardial effusion (PE), particularly in patients with malignancies. This study evaluates the safety and efficacy of PBP in patients with recurrent severe PE. A total of 42 patients with recurrent severe PE underwent PBP between March 2008 and July 2024. PBP was performed under conscious sedation with fluoroscopic guidance using a 20-mm by 60-mm balloon. Data were collected on patient demographics, echocardiographic findings, procedural details, and follow-up outcomes. The study population had a mean age of 58.4 ± 11.2 years, with 54.8% being female. Most patients (76.2%) had malignant PEs. The procedure was technically successful in all cases, with no immediate complications. The median hospital stay was 4 days. Post-procedural transthoracic echocardiography showed no residual effusion in 40.5% of patients and minimal effusion in 50%. Over a median follow-up of 353 days, 54.8% of patients died due to the progression of underlying malignancies, and four patients experienced recurrent effusions requiring additional intervention. PBP is a safe and effective treatment for recurrent severe PE, particularly in patients with malignancies. The procedure's high success rate and favorable safety profile suggest it might be considered a first-line treatment option in appropriate clinical settings.

Hemostatic powder TC-325 as first-line treatment option for malignant gastrointestinal bleeding: a cost-utility analysis in the United Kingdom.

Randomized controlled trials have shown that hemostatic powder (TC-325) results in greater immediate hemostasis and lower 30-day rebleeding rates than standard endoscopic therapy (SET) for management of malignant upper gastrointestinal bleeding (MUGIB). We explored whether TC-325 would be a cost-effective first-line option for patients with MUGIB compared with SET in the United Kingdom. A decision tree was developed for patients with MUGIB, assessing initial therapy with TC-325 or SET over a 30-day period. Patients with failed initial hemostasis or a rebleed within 30 days underwent further endoscopic treatment, escalation to either transcatheter arterial embolization or surgery, or radiotherapy. Overall 30-day mortality was applied. Costs, in GBP, were based on the United Kingdom National Health Services costs for 2023/2024. Results were reported as incremental differences in cost, quality-adjusted life years (QALY), and net monetary benefit. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed. The cost of treating MUGIB patients with TC-325 was £245.88 lower than treatment with SET, with an incremental increase of 0.001 QALYs. TC-325 remained a cost-saving approach in sensitivity and scenario analyses. Probabilistic sensitivity analysis revealed that TC-325 was more effective and cost saving in 80.1% of simulations (range 67.5%-98.63%). Initial treatment of MUGIB with TC-325 compared with SET was more effective (higher primary hemostasis and lower 30-day rebleeding) and cost saving owing to the requirement for fewer interventions, readmissions, and length of stay. Additional studies are needed to address model uncertainties in the follow-up management of these complex patients.

The Role of Image-Guided Superficial Radiation Therapy in the Treatment of Nonmelanoma Skin Cancer

Background: Basal cell carcinoma (BCC) and squamous cell carcinoma, collectively referred to as nonmelanoma skin cancer (NMSC) are the most common type of skin cancer and can lead to significant morbidity and mortality. There are several treatment options available for NMSC including superficial radiation therapy (SRT), which has improved in recent years with the addition of image guidance (IGSRT). In some cases, patients are not offered IGSRT as a treatment option and additional guidance on its benefits may be beneficial. Objective: For a panel of expert dermatologists to review published studies on IGSRT for the treatment NMSC and create consensus recommendations on its use. Methods: A comprehensive literature search of PubMed, EMBASE, Scopus, and Google Scholar was completed for English-language original research articles on the use of IGSRT to treat NMSC. A panel of six dermatologists with significant expertise in treating NMSC convened to review the articles and create consensus statements based on the available data. A modified Delphi process was used to approve each statement for adoption and a strength of recommendation was assigned using Strength of Recommendation Taxonomy (SORT) criteria. Results: After screening the articles that met the initial search criteria, 12 articles were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt eight statements with an additional two statements receiving five out six votes for adoption. Eight of the statements received a strength of recommendation of “A” while two of the statements were given a strength of recommendation of “B” based on SORT criteria. Conclusion: IGSRT is a safe and effective treatment for NMSC that often results in highly favorable cosmetic outcomes. It can be considered a first-line treatment option for appropriately selected cases of NMSC.

Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2-Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial.

Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC. In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m2 once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m2 once on day 1 or paclitaxel 80 mg/m2 once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33. Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin. The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC.

Treatment outcomes of primary salivary gland squamous cell carcinoma: A multi-institutional retrospective study in Japan.

Primary salivary gland squamous cell carcinoma (SCC) is extremely rare, accounting for 0.3-10.4 % of all salivary gland malignancies. Due to this rarity, the clinical characteristics of primary salivary gland SCC remain unelucidated. In the present study, we conducted a multi-institutional retrospective analysis-including a large number of cases compared with that of previous studies-to reveal the prognosis, treatment outcomes, and prognostic factors of primary salivary gland SCC. The clinical course of patients with primary salivary gland SCC between January 2012 and December 2022 was retrospectively investigated. Thirteen university hospitals and cancer centers in Japan participated in this study. The diagnosis of primary salivary gland SCC was based on the following criteria: 1) pathological diagnosis of SCC and exclusion of other histological types and 2) exclusion of metastatic SCCs from other organs. Progression-free and overall survival rates were compared using Kaplan-Meier curves and log-rank tests. Treatment outcomes were assessed using univariate and multivariate analyses with Cox proportional hazards models. In total, 723 patients with salivary gland cancer were admitted to the participating institutions. Among them, 63 patients (8.7 %) were diagnosed with primary salivary gland SCC. The clinical courses of the 58 patients that received definitive treatment and had complete data were analyzed. Primary treatments included surgery in 35 patients (60.3 %), chemoradiotherapy in 16 (27.6 %), radiotherapy in 5 (8.6 %), and chemotherapy in 2 (3.4 %). Complete response and objective response rates to chemoradiotherapy were 62.5 % and 93.8 %, respectively. Five-year progression-free and overall survival rates were 30.1 % and 60.1 %, respectively. Five-year progression-free survival rates for each treatment were 37.7 % (surgery), 33.0 % (chemoradiotherapy), 0 % (radiotherapy), and 0 % (chemotherapy). Overall survival rates were 71.5 % (surgery), 39.5 % (chemoradiotherapy), 53.3 % (radiotherapy), and 0 % (chemotherapy). Multivariate analysis revealed that age ≥70 years, N classification ≥1, and surgery were independent predictors of progression-free (hazard ratios: 3.75, 2.46, and 0.33, respectively) and overall survival (hazard ratios: 3.11, 6.24, and 0.32, respectively). Adjuvant radiotherapy significantly improved progression-free and overall survival in patients with stage Ⅳ cancer or positive surgical margins. Log-rank tests revealed no significant difference between patients with or without elective neck dissection in progression-free and overall survival; however, a relatively high percentage of occult lymph node metastasis (50.0 %) was observed. Surgical resection is a favorable first-line treatment option in salivary gland SCC, and definitive chemoradiotherapy would show acceptable complete and objective response rates.

Oncolytic Viruses and Immunotherapy for the Treatment of Uveal Melanoma and Retinoblastoma: The Current Landscape and Novel Advances.

Intraocular malignant tumors are rare; however, they can cause serious life-threatening complications. Uveal melanoma (UM) and retinoblastoma (RB) are the most common intraocular tumors in adults and children, respectively, and come with a great disease burden. For many years, several different treatment modalities for UM and RB have been proposed, with chemotherapy for RB cases and plaque radiation therapy for localized UM as first-line treatment options. Extraocular extension, recurrence, and metastasis constitute the major challenges of conventional treatments. To overcome these obstacles, immunotherapy, which encompasses different treatment options such as oncolytic viruses, antibody-mediated immune modulations, and targeted immunotherapy, has shown great potential as a novel therapeutic tool for cancer therapy. These anti-cancer treatment options provide numerous advantages such as selective cancer cell death and the promotion of an anti-tumor immune response, and they prove useful in preventing vision impairment due to macular and/or optic disc involvement. Numerous factors such as the vector choice, route of administration, dosing, and patient characteristics must be considered when engineering an oncolytic virus or other forms of immunotherapy vectors. This manuscript provides an in-depth review of the molecular design of oncolytic viruses (e.g., virus capsid proteins and encapsulation technologies, vectors for delivery, cell targeting) and immunotherapy. The most recent advances in preclinical- and clinical-phase studies are further summarized. The recent developments in virus-like drug conjugates (i.e., AU011), oncolytic viruses for metastatic UM, and targeted immunotherapies have shown great results in clinical trials for the future clinical application of these novel technologies in the treatment algorithm of certain intraocular tumors.