Efficacy and safety of the first-line systemic treatments in patients with advanced-stage urothelial carcinoma: a systematic review and network meta-analysis.

Introduction: In recent years, some clinical studies of first-line treatment for advanced-stage urothelial carcinoma (aUC) have reached the main endpoint, showing inconsistent clinical efficacy. We hope to explore the efficacy and safety of first-line treatment for aUC. Methods: The relevant literature from January 2000 to February 2024 was searched, and the R language (version 4.3.1) was used to perform a network meta-analysis based on the JAGS package and GEMTC package under the Bayesian framework. The main indicators included OS, PFS, ORR and adverse events of grade 3 or higher. This study has been registered in PROSPERO (CRD42024525372). Results: A total of 8 RCTs involving 5539 patients and 12 treatments were included. Pembrolizumab plus Enfortumab Vedotin (PEM+EV) was significantly better than other groups in OS, PFS and ORR. In terms of OS, PEM+EV was significantly better than nivolumab plus platinum-based chemotherapy (NIVO+platinumCT) (HR=0.60; 95% CI: 0.45-0.81), PEM+platinumCT (HR=0.55; 95%CI: 0.42-0.72), atezolizumab (ATE) + platinumCT (HR=0.57; 95%CI: 0.43-0.75) and platinumCT (HR=0.47; 95%CI: 0.38-0.58). In terms of PFS, PEM+EV was also significantly better than NIVO+platinumCT (HR=0.62; 95%CI: 0.48-0.82), PEM+platinumCT (HR=0.58; 95%CI: 0.45-0.74), ATE+platinumCT (HR=0.55; 95%CI: 0.43-0.69) and platinumCT (HR=0.45; 95%CI: 0.38-0.54). In terms of ORR, PEM+EV had a significant be nefit compared with other treatment measures, which was 2.63 times that of platinumCT (OR=2.63; 95%CI: 2.00-3.45). The adverse events of grade 3 or higher in immunotherapy (ATE, PEM, durvalumab) was significantly lower than other treatment measures. Conclusions: PEM+EV can significantly prolong OS and PFS compared with other treatments, and has a higher ORR. The adverse events of grade 3 or higher of ATE was the lowest. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024525372, identifier CRD42024525372.

Chemotherapy combined with regorafenib and immune checkpoint inhibitors as a first-line treatment for patients with advanced biliary tract cancer: a single arm phase II trial.

Objective: This study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC). Methods: In this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions. Results: Among the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%). Conclusion: The combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis.

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433-0.973) and 0.682 (95% CI: 0.464-0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511-1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14-3.4) and PFS 2.13 (95% CI: 1.28-3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

First-Line Therapy in Metastatic, RAS Wild-Type, Left-Sided Colorectal Cancer: Should Everyone Receive Anti-EGFR Therapy?

PURPOSE OF REVIEW: This narrative review explores the efficacy and applicability of anti-EGFR therapy as the first-line treatment for patients with RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC). It critically examines current guidelines, along with recent evidence in the literature, to assess whether it should be universally applied. RECENT FINDINGS: Recent evidences highlight the variability of the response to anti-EGFR therapies due to molecular diversity and several clinical factors, such as RAS mutational status and primary tumor location. Anti-EGFR plus chemotherapy is the standard first-line treatment for most patients with MSS, RAS-WT, left-sided mCRC. Whether this combination is the best treatment for these patients remains an open question. This review delves into the role of EGFR inhibition in mCRC, focusing on clinical factors and the knowledge of biology, molecular targets, and biomarkers. It underscores the crucial role of a personalized approach, empowering healthcare providers and equipping them with the confidence to make informed decisions.

Unleashing innovation in first-line healthcare: The barriers to realizing platform openness.

PURPOSE: Digital platforms are essential for fostering innovation in first-line healthcare. These platforms require openness, allowing external parties to utilize, enhance, or profit from them. Yet, knowledge about barriers to realizing platform openness is lacking. This research investigates the barriers to realizing platform openness in first-line healthcare. METHOD: This research employed a qualitative exploratory approach. We collected data through thirteen semi-structured interviews with platform experts, application developers, and healthcare practitioners. As a study setting, we focused on Dutch first-line healthcare. We then analyzed the data using thematic analysis. RESULT: We identify barriers in three main categories that hinder platform openness: technology-related (e.g., redundancy in development work), business-related (e.g., profit-maximizing strategy), and healthcare-related (e.g., reluctance to change). SCIENTIFIC CONTRIBUTION: We contribute to the platform literature in medical informatics by being among the first to examine openness barriers that hinder platform-based innovation. We thus explain why platform implementations often do not result in substantial improvements in healthcare delivery despite their transformative impact in other industries.

TLC-NOSF dressings as a first-line local treatment of chronic wounds: a systematic review of clinical evidence.

OBJECTIVE: Several national and international guidelines recommend lipidocolloid technology with a nano-oligosaccharide factor (TLC-NOSF) dressings (UrgoStart dressing range, Laboratoires Urgo, France) for treating patients with chronic wounds. However, these dressings are still often reported as second-line options, potentially leading to loss of opportunity for patients and additional costs for payers. This review aimed to explore the reported wound healing and patient outcomes as well as the related costs when the dressings were used as first-line treatment in patients with different types of chronic wounds. METHOD: A systematic review of the literature was conducted. Databases (MEDLINE, Embase, Emcare, and Google Scholar) were searched up to 1 February 2024, without any language or time period limitations. Studies were eligible if the evaluated dressings had been used as a first-line treatment for chronic wounds, that is, as an integral part of the standard of care (SoC) at the patient's first presentation and/or in recent wounds. The main evaluation criteria included: wound healing rate; time to reach wound closure; change in patients' quality of life (QoL); and associated costs. The quality of evidence of the included studies was appraised using well-recognised risk-of-bias tools suitable for different study designs. A narrative synthesis describes the findings in three sections depending on the type of comparison. This report followed the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 17 studies published between 2017 and 2024 met the eligibility criteria. A comparative analysis between TLC-NOSF dressings and standard dressings, both of which were used as first-line treatment, was reported in nine studies. A comparative analysis between the use of TLC-NOSF dressings as first-line and second-line treatments was reported in eight studies, and five studies reported a systematic use of the TLC-NOSF dressing as first-line treatment without a control group. Overall, the included studies had a relatively low risk of bias for the respective types of evidence. Data of 10,191 patients of both sexes and different age groups with a total of 10,203 wounds (diabetic foot ulcers, leg ulcers, pressure injuries, and other types of chronic wounds) were included in the analysis: 7775 treated with the evaluated dressing and 2428 treated with a comparator dressing. The data suggested that using TLC-NOSF as a first-line treatment for chronic wounds consistently resulted in significantly higher healing rates, shorter healing times, and cost savings compared with standard dressings used under similar conditions. Real-life evidence confirmed the results obtained in clinical trials and economic models, within similar ranges, regardless of the settings involved or of the characteristics of the patients and wounds treated. The wound healing rates ranged around 70-80% by week 20/24 and time-to-heal was reported on average around seven weeks, with slightly longer times reported in wounds with a more severe prognosis. Furthermore, the dressings were shown to improve patient QoL, and were well tolerated and accepted, supporting a wider adoption approach. CONCLUSION: The results of this review are aligned with the current guidelines recommending the use of TLC-NOSF dressings in the treatment of patients with chronic wounds. They support its wider implementation as a first-line treatment and as an integral part of SoC for these wounds in the daily practice of all centres involved in their management.

Enfortumab vedotin plus pembrolizumab as a first-line treatment for advanced urothelial carcinoma: a cost-effectiveness analysis from China based on the EV-302 trial.

Background: The efficacy and safety of enfortumab vedotin combined with pembrolizumab (EV-PEMB) was investigated as a first-line treatment for advanced urothelial carcinoma (UC) in a phase III clinical trial (EV-302). The trial findings indicated significant prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy with a favorable safety profile. However, EV-PEMB is costly and it is unknown whether it is cost-effective compared to chemotherapy. This study aimed to conduct a cost-effectiveness analysis of EV-PEMB versus chemotherapy as a first-line treatment for advanced UC from the perspective of the Chinese healthcare system. Methods: A Markov model with three distinct health states was developed to assess the cost-effectiveness of EV-PEMB as a first-line treatment for advanced UC versus chemotherapy based on the EV-302 trial. Drug costs were obtained from national tender prices. Other expenses and utility values were sourced from the literature or expert advice. The findings of the study included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We conducted a one-way sensitivity analysis and probabilistic sensitivity analysis to ensure the model's robustness. Results: The EV-PEMB regimen demonstrated a gain of 3.22 QALYs at $375,420.24, compared to the chemotherapy regimen with 1.70 QALYs at $23,369.67. ICER for EV-PEMB compared to chemotherapy was at $232,256.16 per QALY gained. In China, at a willingness-to-pay threshold of $38,133 per QALY, EV-PEMB has a 0% probability of being cost-effective as a first-line treatment for advanced UC compared to chemotherapy. Conclusion: From the perspective of the Chinese healthcare system, EV-PEMB is unlikely to be a cost-effective first-line treatment option for advanced UC compared to chemotherapy.

Systematic review and network meta-analysis of lorlatinib with comparison to other anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) as first-line treatment for ALK-positive advanced non-smallcell lung cancer (NSCLC).

BACKGROUND: Next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) (alectinib, brigatinib, and lorlatinib) demonstrate superior progression-free survival (PFS) over chemotherapy or crizotinib as first-line (1L) treatment of ALK-positive advanced non-smallcell lung cancer (NSCLC). METHODS: We conducted network meta-analyses (NMAs) comparing the relative efficacy of lorlatinib with other ALK TKIs in this indication. Evidence identified from a systematic literature review and subsequent updates formed the basis of our evidence. The primary analysis investigated PFS by independent review committee (IRC) in the intent-to-treat (ITT) population. Secondary outcomes included PFS among subgroups, intracranial time to progression (IC TTP), adverse events, and discontinuation due to adverse events. For each of the outcomes, Bayesian proportional hazards NMAs estimated the relative treatment effects. Additionally, we compared the design and results of eight published NMAs conducted for 1L ALK + advanced NSCLC to date. RESULTS: We formed a network of 10 trials, allowing indirect treatment comparisons. Two trials directly compared alectinib (600 mg twice daily) to crizotinib and one trial directly compared lorlatinib to crizotinib. The results of the NMA show that the hazard ratios (95 % credible interval [CrI]) for ITT PFS IRC were 0.61 (95 % CrI: 0.39, 0.97) when comparing lorlatinib with alectinib (600 mg twice daily) and 0.57 (95 % CrI: 0.35, 0.93) when comparing lorlatinib with brigatinib. In the review of published NMAs, HRs for lorlatinib versus alectinib (600 mg twice daily) and brigatinib were compared. This comparison confirmed that each published NMA yielded similar results. CONCLUSIONS: Our NMA analysis adds to existing findings and supplements data gaps from other published NMAs. Findings from eight published NMAs consistently supported lorlatinib as a clinically effective 1L treatment for ALK + advanced NSCLC patients compared to other TKIs.

Survival analysis of the metastatic cohort of Italian Association of Medical Oncology (AIOM) GARIBALDI survey.

This analysis from the GARIBALDI study was aimed to address the role of center self-declared expertise, type and commitment on the overall survival (OS) of patients with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC). Treatment-naïve patients ≥18-year with pathological diagnosis of mPDAC were enrolled. OS was defined as the time from chemotherapy start to death from any cause. The impact of clinical-demographic and centers characteristics on OS was evaluated using Cox models. Between July 2017 and October 2019, 473 patients enrolled in 43 centers were eligible for this analysis. Median age was 69.3 (first-third quartile 61.2-74.5); 46.1 % females; 90.8 % ECOG PS 0-1; 67.4 % had liver metastases; median CA19.9700.5 UI/mL (first-third quartile 77.5-6629.5). For 37.1 % of patients chemotherapy started <4 weeks from diagnosis; 69.9 % of patients received nab-paclitaxel + gemcitabine; 16.9 % gemcitabine alone; 7.6 % FOLFIRINOX. The median follow-up was 51.8 months and 428 patients died. No statistically significant role of the type of institution was observed. Additionally, no statistically significant role of neither the self-declared expertise nor the accrual rate was observed. The GARIBALDI study suggests that the self-declared center expertise and the academic brand are not associated to OS in patients with mPDAC, while center commitment warrants further exploration.

Clinicopathological features, treatment patterns, and survival outcomes among Syrian patients with advanced breast cancer.

Background: Advanced breast cancer (ABC) is a heterogeneous disease with varied prognoses, that is affected by many clinicopathological features. This study aimed to investigate the clinicopathological characteristics, first-line treatment (FLx), and prognostic impact of these features on survival among Syrian patients with ABC. Materials and methods: This retrospective cohort study included patients with ABC. The association of clinicopathological factors with survival was assessed using Kaplan-Meier curves and the log-rank test, as well as the Cox proportional hazards regression model to calculate the hazard ratio (HaR). Results: A total of 423 patients with ABC were included in the study, with a median age (range) of 47 years (23-82). 83% of metastases were metachronous. Most patients (91.8%) received chemotherapy as the FLx. The median progression-free survival (PFS) and overall survival (OS) of all the patients were 7 and 16 months, respectively. The median PFS was associated with four factors, which were time of metastasis (adjusted HaR=1.861, 95% CI 1.420-2.438, P<0.0001), performance status (PS) (adjusted HaR=1.456, 95% CI 1.049-2.021, P=0.025), ovarian metastasis (adjusted HaR=7.907, 95% CI 1.049-59.576, P=0.045), and FLx (adjusted HaR=2.536, 95% CI 1.581-4.068, P<0.0001). Similarly, the OS was associated with three factors, including hormone receptors (HRs) status (adjusted HaR=1.124, 95% CI 1.009-1.252, P=0.034), time of metastasis (adjusted HaR=2.099, 95% CI 1.588-2.775, P<0.0001), and PS (adjusted HaR=1.787, 95% CI 1.429-2.233, P<0.0001). In the HR-positive/human epidermal growth receptor 2 (HER2)-negative group, endocrine therapy was significantly associated with longer PFS compared with chemotherapy (15 vs 7 months, adjusted HaR=2.699, 95% CI 1.417-5.143, P=0.003). Furthermore, there was no difference in OS between the two treatment modalities (P=0.855). Conclusions: ABC survival varies depending on the location of metastases. Good PS and synchronous stage 4 disease were independent prognostic factors for longer PFS and OS. In the HR-positive/HER2-negative group, PFS for endocrine therapy was significantly longer than chemotherapy, with no differences in OS. This study confirms that endocrine therapy is preferred as an FLx for ABC in the HR-positive/HER2-negative group.

Sunitinib in Patients with Metastatic Renal Cell Carcinoma with Favorable Risk: Be Aware of PD-L1 Expression.

The treatment landscape for metastatic renal cell carcinoma (RCC) has advanced significantly with first-line immunotargeted therapy combinations. However, no statistically significant differences were observed in the cohort of patients with favorable risk and some oncologists continue to use sunitinib in these patients. PD-L1 expression has emerged as a negative prognostic factor in RCC, particularly in sunitinib-treated patients, where higher PD-L1 levels are linked to worse outcomes. This article discusses the potential risks associated with the use of sunitinib in PD-L1-positive patients.

Efficacy and safety evaluation of first-line systemic treatments for unresectable esophageal squamous cell carcinoma: a network meta-analysis.

Objective: To evaluate the efficacy and safety of various first-line initial treatment systemic regimens for patients with unresectable esophageal squamous carcinoma(ESCC), utilizing a network meta-analysis approach. Methods: A comprehensive search for randomized controlled trials focusing on the primary treatment of esophageal cancer ESCC was conducted across multiple databases including PubMed, Embase, Cochrane Library, and Web of Science, up until November 17, 2023. The quality of the included studies was rigorously assessed using Review Manager software. Subsequently, data analysis was meticulously carried out employing R software. The first-line treatment regimens examined were: CD (Cisplatin + Docetaxel), CET-CF (Cetuximab + Cisplatin + Fluorouracil), CF (Cisplatin + Fluorouracil), N-CF (Nivolumab + Cisplatin + Fluorouracil), NI (Nivolumab + Ipilimumab), Nim-CF (Nimotuzumab + Cisplatin + Fluorouracil), P-CF (Pembrolizumab + Cisplatin + Fluorouracil), and Ser-CF (Serplulimab + Cisplatin + Fluorouracil). The Primary endpoints included the overall survival(OS),progression-free survival (PFS),objective response rate (ORR) and disease control rate (DCR).The secondary endpoint was adverse effects(AEs). Results: The analysis encompassed eight studies, incorporating a total of 3,051 patients with untreated esophageal cancer. There are 45 people in the CD regimen,32 in the CET-CF regimen,1,212 in the CF regimen,447 in the N-CF regimen,456 in the NI regimen,53 in the Nim-CF regimen,447 in the P-CF regimen and 368 in the Ser-CF regimen. The network meta-analysis revealed that, in comparison to the CF regimen, the other regimens (CD, CET-CF, N-CF, NI, Nim-CF, P-CF, and Ser-CF) did not demonstrate a statistically significant impact on overall survival (OS) or progression-free survival (PFS). However, Ser-CF potentially offers superior outcomes in terms of OS and PFS when juxtaposed with other regimens. Notably, N-CF was associated with a substantial increase in the objective response rate (ORR), and CET-CF markedly improved the disease control rate (DCR). In terms of adverse effects, N-CF was more likely to cause anorexia, whereas CET-CF was significantly associated with nausea, vomiting, neutropenia, and skin disorders. Conclusion: The current evidence suggests that N-CF may provide the most favorable outcomes in terms of ORR, while CET-CF could be the optimal choice for enhancing DCR in patients with untreated esophageal cancer.

First line therapy in stage IV BRAF mutated colorectal cancer.

Introduction: The molecular profile of colorectal cancer (CRC) plays a crucial role in understanding patient prognosis and treatment response. Within CRC, a distinct subgroup can be identified by the presence of the BRAF V600E mutation. This specific mutation, classified as Class I of BRAF mutations, is known to be associated with a poor prognosis and resistance to standard therapy. To determine the most effective treatment approach for this specific subgroup of CRC, we conducted a network meta-analysis (NMA) to compare various pharmacological interventions and evaluate their relative effectiveness in BRAF-mutated CRCs. Materials and methods: On July 31, 2023, we conducted a systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Embase. The inclusion criteria were as follows: 1) reporting of outcomes in patients with BRAF-mutated CRC who underwent first-line chemotherapy; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. The data were combined using HRs for overall and progression-free survival (OS and PFS) using random-effects models. NMA was performed under the Bayesian framework, utilizing the GeMTC package. The relative rankings of the treatments were determined using SUCRA scores. Results: A total of 16 studies were included. When compared to standard chemotherapy (CT) doublets (such as FOLFOX or FOLFIRI), none of the comparison arms demonstrated a gain in OS. CT doublet + bevacizumab did not show significant superiority over either CT doublet alone or 5FU/capecitabine + bevacizumab. FOLFOXIRI and FOLFOXIRI + bevacizumab did not show superiority over any other treatment schedule that was compared. CT doublets + bevacizumab had the highest SUCRA score (0.87), followed by single-agent fluoropyrimidines + bevacizumab (0.61), and FOLFOXIRI (0.56). Regarding PFS, no regimen was found to be superior to the combination of CT doublet plus bevacizumab. However, FOLFOXIRI + bevacizumab + atezolizumab showed a tendency towards better results (HR = 0.26, 95 % CI 0.05-1.1). Conclusions: Our review suggests that a CT doublet with bevacizumab is the most favorable option for OS. However, a reasonable alternative could be a triplet CT without bevacizumab.

Lorlatinib in the treatment of a rare pulmonary mucoepidermoid carcinoma with EML4-ALK fusion: a case report and literature review.

Pulmonary mucoepidermoid carcinoma (PMEC) is a rare tumor with limited clinical data available due to its low incidence. So far, there are no universal treatment guidelines for this malignant tumor. We present here the case of a 59-year-old female never smoker who was initially referred to our hospital with cough and hemoptysis and was eventually diagnosed with PMEC. Based on further genetic testing, echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) fusion variants E20:A20 (V2) was found. The patient was treated with lorlatinib as the first-line treatment. This case is the first to describe the effectiveness of lorlatinib in treating an advanced high-grade PMEC with EML4-ALK fusion V2 mutation patient.

Cost-effectiveness analysis of durvalumab plus tremelimumab as first-line therapy in patients with unresectable hepatocellular carcinoma.

Background: The HIMALAYA trial found that durvalumab plus tremelimumab significantly prolonged progression-free survival and overall survival in patients with unresectable hepatocellular carcinoma (HCC) compared with sorafenib. Objective: This study aimed to investigate the cost-effectiveness of durvalumab plus tremelimumab compared with sorafenib in the first-line HCC setting. Design: A Markov model-based cost-effectiveness analysis. Methods: We created a Markov model to compare healthcare costs and clinical outcomes of HCC patients treated with durvalumab plus tremelimumab in the first-line setting compared with sorafenib. We estimated transition probabilities from randomized trials. Lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated for first-line durvalumab plus tremelimumab compared with sorafenib from a US payer's perspective. Results: In the base case, first-line durvalumab plus tremelimumab was associated with an improvement of 0.29 QALYs compared with sorafenib. While both treatment strategies were associated with considerable lifetime expenditures, first-line durvalumab plus tremelimumab was less expensive than sorafenib ($188,405 vs $218,584). The incremental net monetary benefit for durvalumab plus tremelimumab versus sorafenib was $72,762 (valuing QALYs at $150,000 each). The results of durvalumab plus tremelimumab were better in terms of costs and health outcomes in patients with HBV-related HCC and high alpha-fetoprotein levels. Conclusion: First-line durvalumab plus tremelimumab was estimated to be dominant for the treatment of unresectable HCC compared with sorafenib from a US payer's perspective.

Clinical efficacy and safety of first-line nilotinib or imatinib therapy in patients with chronic myeloid leukemia-Nationwide real life data.

BACKGROUND: To evaluate the outcomes of first-line imatinib versus nilotinib treatment for chronic myeloid leukemia in the chronic phase (CML-CP) in real-world clinical practice. METHODS: A propensity score analysis was performed to eliminate imbalances between the treatment groups. In the analysis, 163 patients in the nilotinib group and 163 patients in the matched imatinib group were retrospectively evaluated. RESULTS: Nilotinib-treated patients achieved complete cytogenetic response (CCyR) and major molecular response more rapidly than imatinib-treated patients. However, there was no significant difference in 5-year overall survival (OS) or progression-free survival (PFS) between the two groups (OS: 94.3% vs. 90.5%, p = 0.602; PFS: 92.9% vs. 88.0%, p = 0.614). Nilotinib-treated patients had a higher failure-free survival (FFS) and event-free survival (EFS) than imatinib-treated patients (FFS: 71.7% vs. 54.3%, p = 0.040; EFS: 71.7% vs. 53.5%, p = 0.025). CONCLUSIONS: This retrospective analysis from clinical practice did not confirm any benefit of frontline nilotinib treatment for OS and PFS; however, it did demonstrate higher FFS and EFS in the nilotinib cohort.

Efficacy and safety of camrelizumab combined with chemotherapy in the first-line treatment of advanced gastric cancer: a single-arm, phase II study.

Background: Chemotherapy with SOX (S-1 and oxaliplatin) regimen showed good efficacy and a favorable safety profile in advanced gastric cancer. Anti-programmed cell death protein 1 (PD-1) antibody camrelizumab also demonstrated antitumor activity in this setting in a phase I study. However, the efficacy and safety of camrelizumab plus SOX for advanced gastric cancer have not been investigated. Thus, this study aimed to address this objective. Methods: This phase II study evaluated the efficacy and safety of camrelizumab plus SOX in previously untreated advanced gastric cancer. Patients received camrelizumab (200 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, death, or intolerable toxicity. Camrelizumab was prescribed for up to a year. The primary endpoint was progression-free survival (PFS). The second endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 25 patients were enrolled and received at least 1 dose of study drug. The median PFS was 7.4 months [95% confidence interval (CI): 5.6-16.4]. The median OS was 20.2 months (95% CI: 10.5-29.9); ORR was 36% (95% CI: 18.0-57.5%); DCR was 92% (95% CI: 74.0-99.0%). Among the 25 patients, 22 (88%) experienced any-grade adverse events (AEs), and 7 (28%) patients experienced grade ≥3 AEs. Conclusions: Camrelizumab plus SOX showed promising efficacy and an acceptable safety profile as the first-line treatment for advanced gastric cancer.

Four versus six cycles of platinum-based chemotherapy for advanced Urothelial carcinoma in the era of immune checkpoint inhibitors: A retrospective cohort study (FOCUS, KCSG-GU23-08).

INTRODUCTION: This study aimed to assess the survival outcomes of four versus six cycles of first-line platinum-based chemotherapy (PBCT) in the era of immune checkpoint inhibitor (ICI) for patients with advanced urothelial carcinoma (UC). PATIENTS AND METHODS: Patients with histologically confirmed advanced UC were allocated to either the 4-cycle PBCT (C4) or 6-cycle PBCT (C6) groups and retrospectively analyzed. After the planned cycles, active surveillance was conducted every 6-8 weeks, followed by second-line treatments, including ICIs, upon progression. The primary endpoint was overall survival (OS). RESULTS: Of the 161 patients initiated with PBCT between September 2016 and February 2023, 27 were deemed ineligible, leaving 134 patients for analysis (C4, n = 58; C6, n = 77). Baseline characteristics, including cisplatin eligibility, were similar between the groups. With a median follow-up of 23.7 months (95 % confidence interval (CI), 20.3-27.1), no significant difference was observed in OS between the C6 and C4 groups (18.7 months vs. 17.0 months; hazard ratio (HR) 1.27, P = 0.343). In multivariate analysis adjusted for sex, initial presentation, metastatic lesion, and ECOG PS, no significant difference was observed between the C6 and C4 groups (HR 1.29, 95 % CI, 0.78-2.14, P = 0.315). CONCLUSIONS: This study showed that four cycles of PBCT do not differ from six cycles regarding OS.

Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer: a multicenter, open-label, non-inferiority, randomized controlled trial.

Background: The paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy. Methods: This multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer. Results: An analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64-1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen. Conclusion: The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

Good response to cadonilimab as first-line treatment in superaged patient with advanced gastric cancer: a case report.

Gastric cancer remains a considerable global health burden, with limited treatment options available for advanced cases, especially for superaged patients. Cadonilimab, a first-in-class bi-specific antibody (BsAb), offer a promising immunotherapy approach by targeting PD-1/CTLA-4 simultaneously. Herein, we present a case report of an 85-year-old patient with HER2-negative advanced gastric cancer who received first-line treatment with cadonilimab combined with chemotherapy, but cadonilimab was discontinued due to the observation of immune-related pneumonitis during treatment. Despite these changes, the patient still exhibited a stable disease condition for a year until now. This case report highlights the potential of cadonilimab in the treatment of superaged patients with advanced gastric cancer, while the efficacy and safety of it need to be further evaluated.

At present, immunotherapy plus chemotherapy is the standard first-line treatment for patients with advanced gastric cancer. However, immunotherapy is generally not used in elderly patients over 75 years of age due to safety concerns and the treatment options for these patients are very limited. In this paper, we report a case of successful treatment of cadonilimab (novel immunotherapy drug) plus chemotherapy in an 85-year-old male patient with advanced gastric cancer. Until now, the survival time of this patient is over 12 months, and the quality of life is satisfactory.