Anti-Helicobacter pylori Treatment in Patients With Gastric Cancer After Radical Gastrectomy.

Importance: Whether anti-Helicobacter pylori treatment can provide survival benefits for patients with gastric cancer who are diagnosed with H pylori infection is an area with limited research. Objective: To explore the potential survival benefits of anti-H pylori treatment after radical gastrectomy in patients with gastric cancer and presurgical confirmation of H pylori infection. Design, Setting, and Participants: This retrospective cohort study was conducted using data from patients with gastric cancer treated between January 1, 2010, and December 31, 2018, and followed up for outcome ascertainment until May 19, 2021. Propensity score matching was performed in patients treated with or without anti-H pylori treatment. This study involved a single institute in a comprehensive cancer treatment and research center located in Guangzhou, Guangdong Province, China. The study included patients with gastric or esophagogastric junction adenocarcinoma who underwent curative gastrectomy with D2 lymphadenectomy and tested positive for H pylori infection. Data were analyzed from March to June 2023. Exposure: Anti-H pylori treatment, which primarily includes triple therapy regimens consisting of amoxicillin, clarithromycin, and omeprazole for 14 days. Main Outcomes and Measures: Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed by Kaplan-Meier method, log-rank test, and Cox proportional hazards regression model. Subgroup analysis based on crucial clinical information was also conducted. Results: All 1293 patients (median [IQR] age, 59 [50-65] years; 860 [66.5%] male) were divided into 2 groups, with 125 patients in the anti-H pylori treatment group and 1168 patients in the non-anti-H pylori treatment group based on whether they received anti-H pylori treatment during the perioperative period and the follow-up. Survival analysis showed that the 5-year OS rates were 94.1% (95% CI, 89.3%-99.2%) in the anti-H pylori group and 73.8% (95% CI, 70.7%-77.0%) in the non-anti-H pylori group, and the hazard ratio (HR) of these 2 groups was 0.33 (95% CI, 0.18-0.60; P < .001). The survival benefit remained after propensity score matching (HR, 0.50; 95% CI, 0.26-0.99; P = .048). Multivariable analysis for OS and DFS further showed the survival benefit of anti-H pylori treatment, with HRs of 0.38 (95% CI, 0.17-0.87; P = .02) and 0.48 (95% CI, 0.28-0.83; P = .008), respectively. Among patients with TNM stage II/III disease who received adjuvant chemotherapy, anti-H pylori treatment was associated with survival benefits (OS: HR, 0.49; 95% CI, 0.24-0.99; P = .046), whereas among those who did not receive adjuvant chemotherapy, anti-H pylori treatment was not associated with survival benefits (OS: HR, 0.29; 95% CI, 0.04-2.08; P = .22). Conclusions and Relevance: This cohort study indicates that anti-H pylori treatment may be associated with improved survival in patients with gastric cancer who have H pylori infections. The study reinforces the importance of including H pylori screening and treatment in the surgical treatment of these patients.

An interpretable deep learning model for identifying the morphological characteristics of dMMR/MSI-H gastric cancer.

Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

The role of computed tomography features in assessing response to neoadjuvant chemotherapy in locally advanced gastric cancer.

OBJECTIVE: To compare the computed tomography (CT) images of patients with locally advanced gastric cancer (GC) before and after neoadjuvant chemotherapy (NAC) in order to identify CT features that could predict pathological response to NAC. METHODS: We included patients with locally advanced GC who underwent gastrectomy after NAC from September 2016 to September 2021. We retrieved and collected the patients' clinicopathological characteristics and CT images before and after NAC. We analyzed CT features that could differentiate responders from non-responders and established a logistic regression equation based on these features. RESULTS: We included 97 patients (69 [71.1%] men; median [range] age, 60 [26-75] years) in this study, including 66 (68.0%) responders and 31 (32.0%) non-responders. No clinicopathological variable prior to treatment was significantly associated with pathological response. Out of 16 features, three features (ratio of tumor thickness reduction, ratio of reduction of primary tumor attenuation in arterial phase, and ratio of reduction of largest lymph node attenuation in venous phase) on logistic regression analysis were used to establish a regression equation that demonstrated good discrimination performance in predicting pathological response (area under receiver operating characteristic curve 0.955; 95% CI, 0.911-0.998). CONCLUSION: Logistic regression equation based on three CT features can help predict the pathological response of patients with locally advanced GC to NAC.

STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition.

Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double-stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2-deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1-BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2-mutant tumors is elucidated.

Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. METHODS: From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. RESULTS: Compared with ctDNA-negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37-5.48; P = 0.003], while patients with positive post-ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08-72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival (RFS). Moreover, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index (0.78; 95% CI = 0.71-0.84) than the model without ctDNA (0.71; 95% CI = 0.64-0.79; P = 0.009). CONCLUSIONS: Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue-based and circulating tumor features could achieve better risk prediction.

Combined Use of Tumor Markers in Gastric Cancer: A Novel Method with Promising Prognostic Accuracy and Practicality.

BACKGROUND: The effect of a single tumor marker on the prognosis of gastric cancer patients is not ideal. This study explored a novel prognostic assessment method for gastric cancer (GC) patients using a combination of three important tumor markers (CEA, CA72-4, and CA19-9). METHOD: Data from 1966 GC patients who underwent curative gastrectomy at Sun Yat-Sen University Cancer Center (Guangzhou, China) were included. Hazard ratios (HR) for all factors for overall survival (OS) were analyzed by Cox regression. A nomogram and calibration curve were used to establish the survival prediction model. The prediction accuracy was evaluated with the concordance index (C-index). RESULTS: All patients were divided into four groups (C0-C3) according to the number of elevated tumor markers. The 5-year OS rates of the patients in preoperative groups C0-C3 were 83.8% (81.3-86.4%), 72.8% (68.5-77.4%), 58.9% (50.4-68.9%), and 18.5% (4.0-33.0%), respectively, and those in postoperative groups C0-C3 were 82.1% (79.4-84.8%), 76.1% (72.2-80.3%), 57.6% (48.4-68.5%), and 16.8% (5.1-28.5%), respectively, with significant differences between each C0-C3 subgroup in both preoperative and postoperative cohorts. Multivariate analysis showed that preoperative (HR: 6.001, 95% CI: 3.523-10.221) and postoperative (HR: 8.149, 95% CI: 4.962-13.528) elevated tumor markers were independent risk factors for GC patients. The C-index for the combined use of tumor markers was 0.65-0.66, which was higher than that for using a single tumor marker (0.53-0.56). CONCLUSION: The combined use of tumor markers significantly improved the prognostic value compared with using a single tumor marker. The survival prediction model including the combined tumor markers was accurate and effective.

Prognostic Significance of PD-L1 Expression in Gastric Cancer Patients with Peritoneal Metastasis.

BACKGROUND: Recently, many studies have explored the relationship between the expression of programmed death ligand 1 (PD-L1) and prognosis in gastric cancer, but there is still controversy. Additionally, few studies have specifically investigated the expression of PD-L1 in patients with peritoneal metastasis. METHODS: Immunohistochemistry was used to analyze the expression of PD-L1 in gastric cancer patients with peritoneal metastasis. The combined positive score (CPS) was calculated to evaluate the expression of PD-L1, and the clinicopathological data were analyzed to explore prognostic significance. RESULTS: In total, 147 gastric cancer patients with peritoneal metastasis were enrolled. The negative PD-L1 expression was defined as a CPS < 1, and high PD-L1 expression was defined as a CPS ≥ 10. PD-L1 expression with CPS ≥ 1 and CPS-negative was detected in 67 (45.58%) and 80 (54.42%) patients, respectively. High PD-L1 expression at PD-L1 CPS ≥ 10 was detected in 21(14.29%) patients. The median overall survival (OS) was 18.53 months in the CPS < 10 group and 27.00 months in the CPS ≥ 10 group; the OS difference between the two groups was significant (p = 0.015). Multivariate analysis demonstrated that a poor Eastern Cooperative Oncology Group performance score (ECOG PS) (p = 0.002) and severe peritoneal metastasis (p = 0.033) were significantly associated with poor survival, while palliative chemotherapy (p = 0.002) and high PD-L1 expression (p = 0.008) were independent and significantly favorable prognostic factors. CONCLUSIONS: Our study demonstrated that PD-L1 expression was widely presented in gastric cancer patients with peritoneal metastasis, while a CPS no less than 10 predicted better prognosis.

Evaluating relapse-free survival as an endpoint for overall survival in adjuvant immunotherapy trials.

BACKGROUND: Relapse-free survival (RFS) has been considered a primary endpoint to assess the effects of immunotherapy in the adjuvant setting among patients with early-stage disease. However, it is not clear whether RFS is a valid surrogate endpoint for overall survival (OS) in this clinical context. METHODS: Phase II or III clinical trials of adjuvant immunotherapy that reported hazard ratios on OS and RFS were identified. We used a weighted regression analysis at the arm and trial levels to assess the efficacy of RFS as a surrogate for OS, quantified by the weighted coefficient of determination (R2). Strong correlations (R2 ≥ 0.7) at the arm and trial levels indicated valid surrogacy. The surrogate threshold effect was also evaluated. RESULTS: Fifteen high-quality randomized clinical trials involving 13 715 patients were included. At the arm level, moderate and strong associations were observed between RFS2-year and OS3-year (R2 = 0.58, 95% confidence interval [CI] = 0.25 to 0.92) and RFS3-year and OS5-year (R2 = 0.72, 95% CI = 0.38 to 1.00), respectively. At the trial level, a moderate association was observed between effect of treatment on RFS and OS (R2 = 0.63, 95% CI = 0.33 to 0.94). The surrogate threshold effect for RFS was 0.86. Consistent results were confirmed in several sensitivity analyses based on different trial phases, experimental arms, cancer types, and treatment strategies. CONCLUSIONS: Our meta-analysis failed to find a clinically strong association between RFS and OS in randomized clinical trials of adjuvant immunotherapy. Our findings challenge the use of RFS as the primary efficacy endpoint and suggest the use of OS in this clinical context.

Preoperative diagnosis of metastatic lymph nodes by CT-histopathologic matching analysis in gastric adenocarcinoma using dual-layer spectral detector CT.

OBJECTIVES: There still remain challenges to accurate diagnosis of lymph node (LN) involvement in gastric cancer (GC) on conventional CT. This study evaluated the quantitative data derived from dual-layer spectral detector CT (DLCT) for preoperative diagnosis of metastatic LNs compared to conventional CT images. METHODS: Patients with adenocarcinoma scheduled for gastrectomy were enrolled in this prospective study from July, 2021, to February, 2022. Regional LNs were labeled on preoperative DLCT. The LNs were located and matched using carbon nanoparticle solution during surgery according to their locations and anatomic landmarks on preoperative images. The matched LNs were randomly split into training and validation cohorts in a ratio of 2:1. The DLCT quantitative parameters in the training cohort were investigated using logistic regression models to identify independent predictors of metastatic LNs, and these predictors were subsequently applied to the validation cohort. Receiver operating characteristic curves were compared between the DLCT parameters and conventional CT images. RESULTS: Fifty-five patients were included in the study, with 267 successfully matched LNs (90 metastatic, 177 nonmetastatic). Independent predictors included arterial phase CT attenuation on 70-keV images, venous phase electron density, and clustered feature. These combination predictors had areas under the curve (AUC) of 0.855 and 0.907 in the training and validation cohorts, respectively. Compared to conventional CT criteria alone, the model had higher AUC and accuracy (0.741 vs. 0.907, 75.28% vs. 87.64%; p < 0.01) for LN diagnosis. CONCLUSION: Incorporating DLCT parameters improved preoperative diagnosis of LN metastasis in GC, increasing the accuracy of clinical N stage. CLINICAL RELEVANCE STATEMENT: Compared to conventional CT criteria, quantitative parameters from dual-layer spectral detector CT showed higher diagnostic efficacy for the preoperative diagnosis of lymph node metastases in gastric cancer, increasing the accuracy of clinical N stage. KEY POINTS: • Quantitative parameters from dual-layer spectral detector CT are useful for the preoperative diagnosis of lymph node metastases in gastric adenocarcinoma, increasing the accuracy of clinical N stage. • The values for metastatic lymph nodes are higher than those of nonmetastatic ones. The arterial phase of CT attenuation on 70-keV images, venous phase of electron density, and clustered feature independently predicted lymph node metastases. • Prediction model had area under the curve of 0.907, sensitivity of 81.82%, specificity of 91.07%, and accuracy of 87.64% for the preoperative diagnosis of lymph node metastasis.

Predictive value of radiological response, pathological response and relapse-free survival for overall survival in neoadjuvant immunotherapy trials: pooled analysis of 29 clinical trials.

BACKGROUND: An increasing number of clinical trials are being conducted exploring the efficacy of neoadjuvant immune checkpoint inhibitors. Surrogate end-points for overall survival (OS) are urgently needed. METHODS: Phase II or III trials of neoadjuvant immunotherapy that reported data on OS and surrogate end-points were identified from January 1, 2000, to November 25, 2022. Individual patient data, and trial-level data were requested from corresponding authors or extracted from eligible trials. At the individual level, correlations between radiological and pathological response and OS were measured by the Cox model and quantified by hazard ratio (HR). C-statistic was used to quantify the predictive performance of radiological and pathological response for OS. The coefficient of determination (R2) between RFS and OS was evaluated by a bivariate survival model. RESULTS: A total of 29 trials reporting 2901 patients were included. ORR correlated with improved OS (3-year OS: 87.0% versus 70.4% for ORR versus non-ORR, respectively; HR, 0.34, 95% confidence interval [CI], 0.17-0.68). The HRs for OS in patients achieving MPR and pCR were 0.24 (95% CI, 0.12-0.46) and 0.13 (95% CI, 0.05-0.36). The survival benefit maintained after adjusting tumour type. C-statistics of ORR, MPR and pCR were 0.63, 0.63 and 0.65, respectively. The strength of association between RFS and OS was strong (R2 = 0.88, 95% CI, 0.79-0.94). CONCLUSIONS: These findings suggest that ORR, MPR, pCR and RFS are valid predictors for OS when using neoadjuvant immune checkpoint inhibitors. Moreover, MPR, pCR and RFS may be the most optimal surrogates for OS.

Association between Early Immune-Related Adverse Events and Survival in Patients Treated with PD-1/PD-L1 Inhibitors.

BACKGROUND: Immune-related adverse events (irAEs) are side effects that reflect the activation of patients' immune systems after treatment with immune checkpoint inhibitors (ICIs). However, there is no meta-analysis on the effect of early irAEs on patient survival. Thus, we assessed the association between early irAEs and the survival of patients treated with ICIs. METHODS: PubMed, Embase, and Web of Science were searched from May 2010 to May 2020 for all the retrospective and prospective comparative studies to evaluate the hazard ratios (HRs) for death. A random-effects model was used to calculate the pooled HR for death, and heterogeneity was assessed using I² statistics. The main outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 11 reports with 2077 patients were included. A significant association was observed between early irAEs and a favorable clinical outcome. Patients with early irAEs had prolonged OS (HR: 0.62, 95% confidence interval (CI): 0.53-0.74, p < 0.001) and PFS (HR: 0.53, 95% CI: 0.41-0.66, p < 0.001) compared to those without; these results were confirmed using a sensitivity analysis. The irAE types, malignancy types, and sample size were correlated with patients' clinical outcomes. CONCLUSIONS: Early irAEs, especially cutaneous irAEs, correlated with a better clinical outcome in patients treated with ICIs.

Adjuvant Chemotherapy for Patients with Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Multicenter, Observational Study.

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.

Development and verification of a nomogram for predicting the prognosis of resectable gastric cancer with outlet obstruction.

BACKGROUND: The prognosis of patients with gastric cancer (GC) with gastric outlet obstruction (GOO) after gastrectomy is highly variable. In this study, we aimed to develop a nomogram to predict the prognosis of these patients. PATIENTS AND METHODS: Data from 218 GC patients with GOO who underwent gastrectomy at Sun Yat-sen University Cancer Center were retrospectively collected as a training cohort. The data of 59 patients with the same diagnosis who underwent gastrectomy at the First Affiliated Hospital of Guangxi Medical University were collected as an external verification cohort. A nomogram for the overall survival (OS) was developed using the Cox regression model in the training cohort, which was validated in a verification cohort. RESULTS: Multivariate analysis showed that the surgical procedure (P < 0.001), period of chemotherapy (P < 0.001), T stage (P = 0.006), N stage (P = 0.040), systemic immune-inflammatory index (SII) (P < 0.001), and fibrinogen level (P = 0.026) were independent factors affecting OS. The nomogram constructed on the aforementioned factors for predicting the 1- and 3-year OS achieved a Harrell's concordance index (C-index) of 0.756 and 0.763 for the training and verification cohorts, respectively. Compared with the 8th American Joint Committee on Cancer (AJCC) Tumour-Node-Metastasis (TNM) staging system, the nomogram had higher C-index values and areas under the curve (AUCs) and slightly higher net clinical benefit. CONCLUSION: Compared to the 8th AJCC staging system, the newly developed nomogram showed superior performance in predicting the survival of GC patients with GOO after gastrectomy.

LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma: Indirect Cross Comparisons of the CheckMate-067 and RELATIVITY-047 Trials.

Objective: To compare the inhibition of LAG3-PD1 versus the inhibition of CTLA-4-PD1 in patients with previously untreated advanced melanoma. Methods: The individual participant data (IPD) were extracted from the KM plots using a graphical reconstructive algorithm. Log-rank, Cox proportional hazard model, Bayesian hierarchical model with time-varying hazard ratio (HR) effect, and restricted mean survival time (RMST) were performed to estimate survival benefits. Results: The CheckMate-067 (n = 630) and RELATIVITY-047 (n = 714) trials were included for analysis. The graphical reconstructive algorithm showed that IPD had similar HRs and log-rank values as the original plots. The HR of nivolumab plus relatlimab (LAG3 inhibitor) versus nivolumab plus ipilimumab (CTLA4 inhibitor) was 1.19 (95% confidence interval [CI] 0.96 to1.48). The 24-months RMST of nivolumab plus relatlimab versus nivolumab was 2.35 (95% CI 0.77-3.94) months, compared with 1.87 (95% CI, 0.25-3.49) months for nivolumab plus ipilimumab versus nivolumab. The Bayesian hierarchical model showed that patients treated with nivolumab plus relatlimab had earlier PFS benefits than those with nivolumab plus ipilimumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients using nivolumab plus relatlimab and 55.0% of patients using nivolumab plus ipilimumab. Conclusions: These findings suggest that the PFS of LAG3-PD1 and CTLA4-PD1 inhibition were similar and LAG3-PD1 inhibition exhibited earlier survival benefit and lesser TRAEs.