Efficacy Of Checkpoint Inhibitors Research Articles

Integrated multiomics revealed adenosine signaling predict immunotherapy response and regulate tumor ecosystem of melanoma

Extracellular adenosine is extensively involved in regulating the tumor microenvironment. Given the disappointing results of adenosine-targeted therapy trials, personalized treatment might be necessary, tailored to the microenvironment status of individual patients. Here, we introduce the adenosine signaling score (ADO-score) model using non-negative matrix fraction identified patient subtypes using publicly available melanoma dataset, which aimed to profile adenosine signaling-related genes and construct a model to predict prognosis. We analyzed 580 malignant melanoma samples and demonstrated its robust value for prognosis. Further investigation in immune checkpoint inhibitor dataset suggests its potential as a stratified factor of immune checkpoint inhibitor efficacy. We validated the power of the ADO-score at the protein level immunofluorescence in a melanoma cohort from Xiangya Hospital. More importantly, single-cell and spatial transcriptomic data highlighted the cell-specific expression patterns of adenosine signaling-related genes and the existence of adenosine signaling-mediated crosstalk between tumor cells and immune cells in melanoma. Our study reveals a robust connection between adenosine signaling and clinical benefits in melanoma patients and proposes a universally applicable adenosine signaling model, the ADO-score, in gene expression profiles and histological sections. This model enables us to more precisely and conveniently select patients who are likely to benefit from immunotherapy.

Comprehensive analysis of LD-related genes signature for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma

BackgroundLipid droplets (LD) in renal clear cell carcinoma (ccRCC)play a crucial role in lipid metabolism and immune response modulation. The purpose of this study was to create a LD-related signature to predict prognosis and guide the immunotherapy and targeted therapy in ccRCC patients.MethodsWe conducted a comprehensive analysis using transcriptional profiles and clinical data obtained from The Cancer Genome Atlas (TCGA). LD-related genes were identified from existing literature and the GeneCards database, and differentially expressed genes were determined. Sequentially, we conducted Cox regression analysis and Lasso regression analysis, to establish a prognostic risk model. The performance of the risk model was evaluated using Kaplan–Meier (KM) analysis and time-dependent receiver operating characteristic (ROC) analysis. Additionally, gene set enrichment analysis (GSEA), ESTIMATE, CIBERSORT, and immunophenoscore (IPS) algorithm were used to assess the tumor microenvironment (TME) and treatment response.ResultsWe constructed a risk signature with four LD-related genes in the TCGA dataset, which could be an independent prognostic factor in ccRCC patients. Then, patients were classified into two risk groups and exhibited notable differences in overall survival (OS), progression-free survival (PFS), and TME characteristics. Furthermore, we developed a comprehensive nomogram based on clinical features, which demonstrated good prognostic predictive value. According to the results of GSEA analysis, immune-related pathways were found to be significantly enriched in the high-risk group. Additionally, the high-risk group displayed high levels of immune cell infiltration, TMB and IPS scores, indicating better efficacy of immune checkpoint inhibitors (ICIs). Finally, high-risk demonstrated reduced IC50 values compared to the low-risk counterpart for specific targeted and chemotherapeutic drugs, suggesting that the patients receiving these targeted drugs in high-risk group had better treatment outcomes.ConclusionsOur findings suggested that the LD-related gene signature could potentially predict the prognosis of ccRCC patients. Additionally, it showed promise for predicting responses to immunotherapy and targeted therapy in ccRCC patients. These insights might potentially have guided the clinical management of these patients, but further validation and broader data analysis are needed to confirm these preliminary observations.

IDO1 inhibitors are synergistic with CXCL10 agonists in inhibiting colon cancer growth

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immune checkpoint that degrades L-tryptophan to kynurenine (Kyn) and enhance immunosuppression, which can be an attractive target for treating colon cancer. IDO1 inhibitors have limited efficacy when used as monotherapies, and their combination approach has been shown to provide synergistic benefits. Many studies have shown that targeting chemokines can promote the efficacy of immune checkpoint inhibitors. Therefore, this study explored the use of IDO1 inhibitors with multiple chemokines to develop a new combination regimen for IDO1 inhibitors. We found that IDO1 inhibitors reduce the secretion of C-X-C motif ligand 10(CXCL10) in cancer cells, and CXCL10 supplementation significantly improved the anticancer effect of IDO1 inhibitors. The combination of the IDO1 inhibitor with CXCL10 or its agonist axitinib had a synergistic inhibitory effect on the growth of colon cancer cells and transplanted CT26 tumors. This synergistic effect may be achieved by inhibiting cancer cell proliferation, promoting cancer cell apoptosis, promoting CD8+T cell differentiation and decreasing Tregs. Two downstream pathways of IDO1 affect CXCL10 secretion. One being the Kyn-aryl hydrocarbon receptor (AHR) pathway, the other is the general control nonderepressible 2(GCN2). Our study provides a new reference for combination regimens of IDO1 inhibitors.

Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-Type Non-Small Cell Lung Cancer.

Treatment of non-small cell lung cancer (NSCLC) has drastically changed in recent years owing to the robust anticancer effects of immune checkpoint inhibitors (ICI). However, only 20% of the patients with NSCLC benefit from ICIs, highlighting the need to uncover the mechanisms mediating resistance. By analyzing the overall survival (OS) and mutational profiles of 424 patients with NSCLC who received ICI treatments between 2015 and 2021, we determined that patients carrying a loss-of-function mutation in neurotrophic tyrosine kinase receptor 1 (NTRK1) had a prolonged OS when compared with patients with wild-type NTRK1. Notably, suppression of the NTRK1 pathway by knockdown or entrectinib treatment significantly enhanced ICI efficacy in mouse NSCLC models. Comprehensive T-cell population analyses demonstrated that stem-like CD4+ T cells and effector CD4+ and CD8+ T cells were highly enriched in anti-PD-1-treated mice bearing tumors with decreased NTRK1 signaling. RNA sequencing revealed that suppression of NTRK1 signaling in tumor cells increased complement C3 expression, which enhanced the recruitment of T cells and myeloid cells and stimulated M1-like macrophage polarization in the tumor. Together, this study demonstrates a role for NTRK1 signaling in regulating cross-talk between tumor cells and immune cells in the tumor microenvironment and provides a potential therapeutic approach to overcome immunotherapy resistance in patients with NSCLC with NTRK1 wild-type. Significance: Inhibition of NTRK1 signaling confers sensitivity to immunotherapy by enhancing complement C3-mediated T-cell and macrophage functions, leading to improved responses to immune checkpoint inhibitors in patients with lung cancer with NTRK1 mutations.

Suppression of double-stranded RNA sensing in cancer: molecular mechanisms and therapeutic potential.

Immunotherapy has emerged as a therapeutic option for many cancers. For some tumors, immune checkpoint inhibitors show great efficacy in promoting anti-tumor immunity. However, not all tumors respond to immunotherapies. These tumors often exhibit reduced inflammation and are resistant to checkpoint inhibitors. Therapies that turn these 'cold' tumors 'hot' could improve the efficacy and applicability of checkpoint inhibitors, and in some cases may be sufficient on their own to promote anti-tumor immunity. One strategy to accomplish this goal is to activate innate immunity pathways within the tumor. Here we describe how this can be accomplished by activating double-stranded RNA (dsRNA) sensors. These sensors evolved to detect and respond to dsRNAs arising from viral infection but can also be activated by endogenous dsRNAs. A set of proteins, referred to as suppressors of dsRNA sensing, are responsible for preventing sensing 'self' dsRNA and activating innate immunity pathways. The mechanism of action of these suppressors falls into three categories: (1) Suppressors that affect mature RNAs through editing, degradation, restructuring, or binding. (2) Suppressors that affect RNA processing. (3) Suppressors that affect RNA expression. In this review we highlight suppressors that function through each mechanism, provide examples of the effects of disrupting those suppressors in cancer cell lines and tumors, and discuss the therapeutic potential of targeting these proteins and pathways.

Clinical outcomes of first-line combination therapy with immune checkpoint inhibitor for metastatic non-clear cell renal cell carcinoma: a multi-institutional retrospective study in Japan

BackgroundIn metastatic clear cell renal cell carcinoma (ccRCC), recent studies have shown promising efficacy of immune checkpoint inhibitor (ICI) combination therapy. However, there are insufficient evidences about clinical efficacy and safety of ICI combination therapy in metastatic non-ccRCC (nccRCC).MethodsWe retrospectively investigated 44 patients treated with nivolumab plus ipilimumab (ICI + ICI group) or anti-PD-1/PD-L1 inhibitor plus tyrosine kinase inhibitors (TKI) (ICI + TKI group), and assessed clinical efficacy in both groups.ResultsOf all patients, overall response rate and disease control rate for ICI combination treatments were 36.3% and 75%, respectively. The median progression-free survival (PFS) and overall survival (OS) was 8.8 and 23.9 months, respectively. Multivariate analysis revealed that the presence of liver metastasis significantly affected worse PFS and OS (p = 0.035 and p = 0.049). Importantly, PFS and OS seemed similar in ICI + ICI group and ICI + TKI group (p = 0.778 and p = 0.559). Although the discontinuation rate of the combination therapy due to adverse effects in patients aged ≥ 75 years was significantly higher compared to that in patients aged < 75 years (45% versus 12%, p = 0.017), there were no significant differences in PFS and OS between two groups (p = 0.290 and p = 0.257, respectively).ConclusionThis study confirms clinical benefit of ICI combination therapy for metastatic nccRCC patients in real-world settings. Furthermore, the effectiveness of combination therapy was comparable between patients aged < 75 and those ≥75 years with respect to clinical prognosis.

Enhancing outcomes in extensive-stage small cell lung cancer brain metastases: a retrospective study on the synergistic effects of immune checkpoint inhibitor, brain radiotherapy, and chemotherapy.

Brain metastasis is a frequent complication in small cell lung cancer (SCLC), and there is an urgent need for new treatment modalities, given the limited success of traditional approaches. This study evaluates the combined efficacy and safety of brain radiotherapy (BRT), chemotherapy, and immune checkpoint inhibitors (ICIs) in the treatment of brain metastases in patients with extensive-stage SCLC (ES-SCLC). Additionally, it seeks to identify prognostic factors in these cases. A retrospective analysis was performed on 187 patients with ES-SCLC and brain metastases treated at Zhejiang Cancer Hospital from January 2017 to October 2023. Patients were divided into three groups based on their initial treatment: BRT alone, ICI alone, and a combined ICI + BRT approach, with chemotherapy included in all regimens. Variables such as age, number of brain metastases, symptoms, comorbidities, Karnofsky Performance Status (KPS) scores, smoking history, Graded Prognostic Assessment (GPA) scores, survival time, and treatment-related adverse events (TRAEs), including hematologic and hepatic toxicities were evaluated. Prognostic factors were assessed using univariate and multivariate analyses via Cox's proportional hazards model. The study also compared outcomes and TRAEs between patients undergoing synchronous treatment (ICI and BRT within four weeks) versus those with asynchronous therapy (more than four weeks apart). Median overall survival (OS) times differed significantly across the groups: 11.6 months for BRT, 11.6 months for ICI, and 20.9 months for ICI + BRT (P<0.001). The ICI + BRT group also exhibited notably better progression-free survival (PFS) and intracranial PFS (iPFS), with medians of 12.6 and 14.9 months, respectively (P<0.001). This group demonstrated significantly improved systemic and intracranial objective response rates (ORR) and disease control rates (DCR). No significant differences in acute radiation injury rates were observed between the BRT and ICI + BRT groups. Multivariate analysis identified several factors influencing OS, including treatment regimen, number of chemotherapy and ICI cycles, presence of bone and multiple brain metastases, and antiangiogenesis therapies and extracranial radiotherapy. Both atezolizumab and serplulimab ICIs, in combination with various radiotherapy regimens [whole BRT (WBRT), WBRT with boost], were effective. Notably, asynchronous ICI and BRT treatment demonstrated advantages in PFS and iPFS over concurrent therapy, with no significant differences in other therapeutic indices or TRAE incidence rates. For ES-SCLC patients with synchronous brain metastases, combined ICI and BRT, alongside chemotherapy, surpasses the efficacy of either treatment alone with manageable TRAEs. Importantly, asynchronous ICI and BRT therapy showed superior outcomes compared to synchronous treatment modalities.

535P Safety and efficacy of first-line immune checkpoint inhibitors in elderly colorectal cancer patients: An Italian real-world multicenter experience

535P Safety and efficacy of first-line immune checkpoint inhibitors in elderly colorectal cancer patients: An Italian real-world multicenter experience

1848P Safety and efficacy of immune checkpoint inhibitors in patients with cancer and hepatitis B: Multicentre experience

1848P Safety and efficacy of immune checkpoint inhibitors in patients with cancer and hepatitis B: Multicentre experience

1847P Safety and efficacy of immune checkpoint inhibitors in patients over 85 years: ICIPO85 study

1847P Safety and efficacy of immune checkpoint inhibitors in patients over 85 years: ICIPO85 study

798. FEASIBILITY AND EFFICACY OF CISPLATIN, PACLITAXEL AND IMMUNE CHECKPOINT INHIBITORS AS CONVERSION THERAPY FOR LOCOREGIONALLY UNRESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Induction therapy followed by conversion surgery is potentially curative for locoregionally unresectable esophageal squamous cell carcinoma (ESCC). However, the optimal induction treatment strategy is unclear. The study aimed to evaluate the feasibility and efficacy of cisplatin, paclitaxel and immune checkpoint inhibitors as conversion therapy for locoregionally unresectable ESCC. Methods Clinicopathological variables of cT4b ESCC patients who received neoadjuvant chemoimmunotherapy were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. Enhanced computed tomography, ultrasonography and bronchoscopy were routinely used for the diagnosis. The treatment protocol of neoadjuvant chemoimmunotherapy included 2 cycles of immunotherapy plus chemotherapy with the interval of 3 weeks among each cycle. All patients received 2 cycles of Pembrolizumab (200 mg, D1), Sintilimab (200 mg, D1), Tislelizumab (200 mg, D1) or Camrelizumab (200 mg, D1) intravenously. Concurrently all patients received 2 cycles of cisplatin (75 mg/m2 of body-surface area, D1) and paclitaxel (175 mg/m2 body-surface area, D1) intravenously. The perioperative parameters and short-term surgical outcomes were presented (Table). Results Between January 2020 and December 2022, a total of 317 ESCC patients who underwent neoadjuvant chemoimmunotherapy followed by surgery were screened. Twenty cT4b patients with middle or upper thoracic ESCC were finally enrolled in this study. Pretreatment tumor invades the trachea (4, 20%), left main bronchus (16, 80%), and aorta (6, 30%), respectively. All the patients were successfully performed by McKeown minimally invasive esophagectomy except for one patient conversion to thoracotomy. R0 resection was achieved in 15 patients, 4 patients underwent R1 resection and 1 patient underwent R2 resection. Mean operation duration was 290.4 ± 57.5 min. Mean estimated blood loss was 94.4 ± 108.8 ml. Three patients had postoperative pneumonia, two patients had postoperative pleural effusion and one patient had postoperative recurrent laryngeal nerve paralysis. No patient had postoperative anastomotic leak. No postoperative reoperation was needed and there was no perioperative mortality. Mean length of hospital stay was 10.9±1.4 days. 90-day mortality occurred in one patient with postoperative multiple systemic metastasis. Fifteen patients are alive with a median follow up of 18 months. One patient died with regional lymph node recurrence and three patients died with hematogenous dissemination. Conclusion Multimodal treatment strategy combining immunotherapy and chemotherapy may convert unresectable tumors into potentially operable ones, and achieved favorable survival. Longer follow-up and larger sample size are needed to verify our preliminary results.

142P Exploring tumor mutational burden and frameshift mutations as predictors of immune checkpoint inhibitor efficacy

142P Exploring tumor mutational burden and frameshift mutations as predictors of immune checkpoint inhibitor efficacy

1354P Retrospective audit to determine the effect of antibiotic therapy on immune checkpoint inhibitor efficacy in stage IV NSCLC

1354P Retrospective audit to determine the effect of antibiotic therapy on immune checkpoint inhibitor efficacy in stage IV NSCLC

Efficacy and safety of immune checkpoint inhibitors plus platinum-etoposide vs. platinum-etoposide in the first-line treatment of extensive-stage small cell lung cancer: a systematic review and a meta-analysis.

Currently, immune checkpoint inhibitors (ICIs) combined with platinum-etoposide (EP) are gradually becoming the first-line standard treatment for extensive-stage small cell lung cancer (ES-SCLC). This meta-analysis aims to compare the efficacy and safety of ICIs combined with EP vs. EP alone in the first-line treatment of ES-SCLC. We searched PubMed, Embase, and Cochrane Library databases for phase II/III randomized controlled trials (RCTs) that met inclusion criteria from January 2016 to November 2023. Outcome measures included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), treatment-related adverse events (TRAEs), treatment-related serious adverse events (TRSAEs), and immune-related adverse events (IRAEs). The effect analysis statistics of the outcome indicators were expressed with hazard ratio (HR) and odds ratio (OR) and their 95% confidence interval (CI). This study included nine RCTs with a total of 4,711 patients. Compared to EP, ICIs plus EP improved patients' PFS (HR =0.71; 95% CI: 0.64-0.79; P<0.001), OS (HR =0.79; 95% CI: 0.74-0.84; P<0.001), and ORR (OR =1.27; 95% CI: 1.12-1.44; P=0.001), but increased the incidence of adverse events (AEs): TRAEs (OR =1.45; 95% CI: 1.20-1.76; P<0.001), IRAEs (OR =3.97; 95% CI: 2.49-6.32; P<0.001), and grade 3-4 IRAEs (OR =6.17; 95% CI: 2.36-16.15; P<0.001). However, there was no significant difference in the incidence of grade 3-4 TRAEs (OR =1.05; P=0.54), TRSAEs (OR =1.40; P=0.13), and grade 3-4 TRSAEs (OR =1.17; P=0.72). Subgroup analysis found that patients with brain metastasis did not benefit from ICIs combined with EP therapy, and patients with programmed cell death ligand 1 (PD-L1) expression ≥1% had poorer survival benefits compared to patients with PD-L1 expression <1%. In the first-line treatment of ES-SCLC, compared to EP chemotherapy, ICIs with EP can benefit patients in terms of PFS, OS, and ORR, but it will increase the occurrence of AEs.

Mutant p53 Exploits Enhancers to Elevate Immunosuppressive Chemokine Expression and Impair Immune Checkpoint Inhibitors in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective treatments. It is characterized by activating KRAS mutations and p53 alterations. However, how these mutations dysregulate cancer-cell-intrinsic gene programs to influence the immune landscape of the tumor microenvironment (TME) remains poorly understood. Here, we show that p53R172H establishes an immunosuppressive TME, diminishes the efficacy of immune checkpoint inhibitors (ICIs), and enhances tumor growth. Our findings reveal that the upregulation of the immunosuppressive chemokine Cxcl1 mediates these pro-tumorigenic functions of p53R172H. Mechanistically, we show that p53R172H associates with the distal enhancers of the Cxcl1 gene, increasing enhancer activity and Cxcl1 expression. p53R172H occupies these enhancers in an NF-κB-pathway-dependent manner, suggesting NF-κB's role in recruiting p53R172H to the Cxcl1 enhancers. Our work uncovers how a common mutation in a tumor-suppressor transcription factor appropriates enhancers, stimulating chemokine expression and establishing an immunosuppressive TME that diminishes ICI efficacy in PDAC.

Utility of Assessing Early Tumor Shrinkage as an Efficacy Predictor in Patients with Non-Surgically Indicated or Recurrent Esophageal Cancer Treated with Nivolumab plus Ipilimumab.

Nivolumab plus ipilimumab combination therapy has been administered as a first-line treatment in Japan since 2022 for patients with unresectable progressive or recurrent esophageal cancer. The efficacy and safety of this immune checkpoint inhibitor (ICI) doublet therapy are now being evaluated, and it is necessary to identify populations that benefit from this treatment at an early phase after initiation. For patients not showing early benefit, changing as soon as possible to other therapeutic strategies could improve their survival outcomes. Therefore, we attempted to identify decision-making factors such as early tumor shrinkage (ETS) based on treatment experience with ICI doublet therapy. The study included 19 patients who received nivolumab plus ipilimumab for non-surgically indicated or recurrent esophageal cancer between July 2022 and November 2023. Tumors were assessed approximately every 2 months after treatment initiation. The effects of ETS, depth of response (DpR), and clinicopathologic features, including immune-related adverse events (irAEs), on progression-free and overall survival were evaluated using Kaplan-Meier plots and Cox proportional hazard models. The mean duration of ICI doublet administration was 5.89 months (range, 1-16 months). At first evaluation, patients who exhibited no tumor progression &gt;20% indicated possible response to ICI doublet therapy, and patients whose tumors shrank even minimally exhibited favorable progression-free survival. Higher DpR at any cut-off line exhibited better progression-free survival than those with lower DpR. Fifteen patients experienced irAEs, with 13 of these patients experiencing irAEs within 3 months of treatment initiation. irAEs were associated with the efficacy of ICI doublet therapy, but efficacy could not be predicted based on early irAE experience. ETS-high, DpR-high, and irAEs might be associated with favorable responses to nivolumab plus ipilimumab. As a predictor of efficacy at an early phase, ETS &gt;0% could be a deciding factor for continuing ICI doublet therapy.

Focal Update on Immunotherapy and Liver Transplantation in the Era of Transplant Oncology.

Transplant oncology is an expanding area of cancer therapy that specifically emphasizes the use of liver transplantation (LT) as the preferred treatment for patients with manageable, but unresectable, tumors. The management and optimization of overall survival strategies, accompanied by an arguably decent quality of life, have been at the forefront of liver oncology treatment, as a plurality of all primary liver cancers are identified as either hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA), which are classified as highly aggressive malignancies and frequently remain asymptomatic until they progress to advanced stages, rendering curative procedures, such as resection, impractical. This has led to an increase in utilization of neoadjuvant interventions conducted prior to surgery, which has yielded favorable outcomes. Though this treatment modality has prompted further investigations into the efficacy of immune checkpoint inhibitors (ICPIs) as standalone treatments and in combination with locoregional treatments (LRTs) to bridge more patients into curative eligibility. This multidisciplinary methodology and treatment planning has seen multiple successful trials of immunotherapy regimes and combinate treatments, setting the groundwork for increasing eligibility through downstaging and "bridging" previously ineligible patients within stringent LT criteria. Surveillance after LT is a crucial component of transplant oncology. The emergence of circulating tumor DNA (ctDNA) has provided a novel approach to identifying the recurrence of cancer in its early stages. Recent research has focused on liquid biopsy, a technique that effectively identifies the dynamics of cancer. This is another innovation to demonstrate the rate at which transplant oncology is rapidly advancing, making the focus of care feel disorienting. Modalities of care are constantly evolving, but when a field is changing as rapidly as this one, it is imperative to reorient to the data and the needs of the patients. In this commentary, we reflect on the update's utilization of ICPIs in neoadjuvant settings as well as the updates on the utilization of liquid biopsy in post-LT follow-up surveillance.

Low dose radiation can improve the therapeutic efficacy of immune checkpoint inhibitor in a mouse anaplastic thyroid cancer model

Low dose radiation can improve the therapeutic efficacy of immune checkpoint inhibitor in a mouse anaplastic thyroid cancer model

Analysis of immune checkpoint inhibitors for advanced non-small cell lung cancer in patients receiving antacids

BackgroundProton pump inhibitors (PPIs) are reported to decrease the efficacy of immune checkpoint inhibitors (ICIs), but there are few reports on the association between ICI efficacy and antacids other than PPIs, and simultaneous examination of the effects of antacids, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) on ICI therapy. MethodsWe conducted a retrospective study of 381 patients with non-small cell lung cancer who received ICI therapy from January 1, 2016 to December 31, 2022. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Antacids included histamine type 2 receptor antagonists (H2RAs), PPIs, and potassium-competitive acid blockers (P-CABs). ResultsAntacids were administered to 218 patients, including 168 with PPIs, 37 with P-CABs, and 13 with H2RAs. Patients with antacids had worse median PFS and OS than those without antacids (PFS, 2.9 vs. 6.2 months; OS, 12.3 vs. 24.0 months), and those with PPIs, P-CABs, or H2RAs had similar results. However, there were no significant differences between patients with and without antacids when stratified by corticosteroid and NSAID use. Multivariate analyses showed that corticosteroids and NSAIDs administered for cancer-associated symptoms were related to poor prognosis, but antacids including PPIs, P-CABs, or H2RAs were not related. ConclusionsAntacids were not related to ICI efficacy when NSAIDs or corticosteroids were taken into consideration. This may be because the most frequent reason for administering NSAIDs and corticosteroids was cancer-associated symptoms, which are a poor prognostic factor, and most of the patients treated with these medications also received antacids.

Clinical predictive factors of the efficacy of immune checkpoint inhibitors and kinase inhibitors in advanced hepatocellular cancer.

Hepatocellular carcinoma (HCC) is a highly aggressive tumor associated with significant morbidity and mortality rates. Combination therapy with immune checkpoint inhibitors (ICIs) and kinase inhibitors has emerged as a promising strategy for liver cancer treatment in recent years. However, the clinical factors predicting the outcomes of combination therapy in patients with advanced liver cancer remain uncertain. Therefore, this study investigated the relationships between clinical predictors and the efficacy of ICI plus kinase inhibitor therapy to personalize treatment plans. We retrospectively enrolled 98 patients who received combination treatment with ICIs and kinase inhibitors for advanced HCC. Based on blood lipid levels and other clinical factors prior to treatment, we investigated potential biomarkers that could predict treatment responses in this patient population. Mean progression-free survival (PFS) and overall survival (OS) in this cohort were 10.1 and 17.2months, respectively. Via multivariate analysis, the absence of extrahepatic metastasis, the absence of portal vein thrombosis (PVT), neutrophil-to-lymphocyte ratio (NLR) < 3.225, platelet-to-lymphocyte ratio (PLR) < 140.75, and prognostic nutritional index (PNI) ≥ 37.25 were identified as independent predictors of improved PFS. Factors associated with better OS included PLR < 140.75 and total cholesterol (TC) < 3.46mmol/L. Univariate analysis identified significant associations of Eastern Cooperative Oncology Group performance status (ECOG PS), hepatitis B virus (HBV) DNA levels, Child-Pugh classification, alpha-fetoprotein (AFP), TC, and the receipt of regorafenib with PFS. Additionally, ECOG PS, Child-Pugh classification, AFP, PVT, NLR, PNI, and the receipt of regorafenib were significantly associated with OS. PLR and TC were potential clinical predictive factors for survival outcomes in patients with advanced HCC who received ICI/kinase inhibitor combination therapy. It is important to know the clinical characteristics of patients prior to treatment initiation to optimize outcomes.