Clinical features as prognostic markers in patients with solid tumors treated with programmed cell death protein 1/programmed cell death-ligand 1 inhibitors: a retrospective cohort study

Evidence from clinical research and meta-analyses have suggested that programmed cell death 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors plus chemotherapy could achieve a significant survival benefit for extensive-stage small-cell lung cancer (ES-SCLC) patients. However clinical researches concerned about the comparation between the PD-1 and PD-L1 inhibitors were relatively lacking. We collected the data of ES-SCLC patients treated with PD-1 inhibitors or PD-L1 inhibitors. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint included adverse events (AEs). The data of 221 ES-SCLC patients treated with PD-1 (n=146) or PD-L1 inhibitors (n=75) between February 2017 and June 2020 were retrospectively collected. The median OS (mOS) and median PFS (mPFS) were 19.07 and 8.27 months, respectively, in patients treated with PD-1 inhibitors. In the PD-L1 group, mOS has not been reached, and mPFS was 7.95 months. No significant differences were observed between the 2 groups in OS [hazard ratio (HR), 1.472; 95% confidence interval (CI), 0.847-2.220; P=0.198] and PFS (HR, 0.816; 95% CI, 0.577-1.155; P=0.251). The rates of patients showed AEs of any grade treated with PD-1 or PD-L1 were 67.12% and 64.00%, with no significant difference (P=0.642, χ2=0.216), ≥3 grade AEs occurred in 42 (28.76%) and 16 (21.33%) patients treated with PD-1 and PD-L1 inhibitors separately, also no significant difference (P=0.234, χ2=1.415) was observed. According to subgroup analysis, camrelizumab revealed a longer mPFS (15.17 months) compared with other immune-checkpoint inhibitors (ICIs). PD-1 and PD-L1 inhibitors revealed comparable efficacy in ES-SCLC patients with brain metastases, with no significant differences in OS (HR, 1.505; 95% CI, 0.684-3.311; P=0.309) and PFS (HR, 0.649; 95% CI, 0.356-1.182; P=0.157). PD-1 and PD-L1 inhibitors might achieved comparable survival benefit and safety in ES-SCLC patients. A longer PFS was observed in patients treated with PD-1 inhibitors in the first-line treatment, and the PD-1 inhibitor camrelizumab might have achieved a better PFS compared with other ICIs.

Funding Acknowledgements Type of funding sources: None. OnBehalf Cardiovascular Analytics Group Background Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, they are associated with adverse cardiovascular events. Purpose To evaluate the cardiotoxicity of PD-1 and PD-L1 inhibitors, the present study aims to examine the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors. Methods Patients receiving PD-1 or PD-L1 inhibitors since their launch up to December 31st, 2019 without pre-existing cardiac complications were included. Patient data were obtained using a territory-wide electronic health record database. The primary outcome was a composite of incident heart failure (HF), acute myocardial infarction (AMI), atrial fibrillation (AF) or atrial flutter followed up to August 31st, 2020. Propensity score matching between PD-L1 and PD-1 inhibitor use with a 1:1 ratio for patient demographics and comorbidities was performed. Results A total of 1925 patients were included. Over a median follow-up of 136 days (interquartile range [IQR]: 42-279), 318 (16.51%) patients met the primary outcome after PD-1/PD-L1 treatment: 242 (incidence rate [IR]: 12.57%) with HF, 38 (IR: 1.97%) with AMI, 53 (IR: 2.75%) with AF, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with a lower risk of composite outcome after matching (HR: 0.78, 95% CI: [0.62-0.99], P value = 0.0417). Patients who developed cardiovascular complications had shorter average readmission intervals and more hospitalization episodes after treatment with PD-1/PD-L1 inhibitors both before and after matching (P value < 0.0001). Conclusions Compared with PD-1 inhibitor users, PD-L1 inhibitor users had a significantly lower risk of new-onset composite cardiovascular complications. Abstract Figure. Kaplan-Meier survival curve

8086 Background: Addition of programmed cell death ligand 1 (PD-L1) inhibitors or programmed cell death 1 (PD-1) inhibitors to etoposide‐platinum (EP) chemotherapy has become the standard first-line regimen for ES-SCLC. The clinical efficacy and safety between the two types of immune checkpoint inhibitors (ICIs) remain controversial. We conduct the retrospective study and propensity score-matched analysis to explore the potential differences between them. Methods: Patients diagnosed with ES-SCLC and treated by EP plus PD-L1 or PD-1 inhibitors at Shandong Cancer Hospital between March 2019 and November 2022 were reviewed retrospectively. According to PD-L1 or PD-1 inhibitors, they were divided into two groups. Propensity score matching (1:1) was performed to balance the baseline characteristics of the two groups. The baseline characteristics and adverse events between the two groups were compared using the chi-squared test. The survival curves of overall survival (OS) and progression-free survival (PFS) were plotted by the Kaplan-Meier method and differences were analyzed by the log-rank test.The primary endpoints were OS and PFS. Results: As a result, 448 patients were analyzed in this study. 264 patients received PD-L1 inhibitors plus EP and 184 received PD-1 inhibitors plus EP. The median follow-up was 17.6 months. The median OS and PFS was 20.4 months and 7.8 months in the overall population. Before propensity score matching, the median OS was 20.1 months in PD-L1 inhibitor plus EP group and 20.7 months in PD-1 inhibitor plus EP group, respectively (HR 1.043, 95%CI 0.776-1.401; p= 0.781). The median PFS was 7.6 months in the PD-L1 inhibitor plus EP group and 8.5 months in PD-1 inhibitor plus EP group (HR 1.099, 95%CI 0.886-1.364; p= 0.390). After propensity score matching, the median OS and PFS were 20.4 months and 7.8months in PD-L1 inhibitor plus EP group, and those were 20.1 months and 8.6 months in PD-1 inhibitor plus EP group. There was no significant difference in OS and PFS between PD-L1 inhibitors plus EP and PD-1 inhibitors plus EP in the matched population (HR 1.104; p= 0.578 and HR 1.072; p= 0.602, respectively). The overall adverse events were comparable in the two groups. Only ≥3 grade neutropenia was more frequent in the PD-L1 inhibitors plus EP group (77.7% vs 69.0%, p= 0.040). Conclusions: In conclusion, the overall efficacy and safety profile was similar between PD-L1 inhibitors and PD-1 inhibitors for the first-line treatment of ES-SCLC.

206 Background: Addition of programmed cell death ligand 1 (PD-L1) inhibitors or programmed cell death 1 (PD-1) inhibitors to etoposide‐platinum (EP) chemotherapy has become the standard first-line regimen for ES-SCLC. The clinical efficacy and safety between the two types of immune checkpoint inhibitors (ICIs) remain controversial. We conduct the retrospective study and propensity score-matched analysis to explore the potential differences between them. Methods: Patients diagnosed with ES-SCLC and treated by EP plus PD-L1 or PD-1 inhibitors at Shandong Cancer Hospital between March 2019 and November 2022 were reviewed retrospectively. According to PD-L1 or PD-1 inhibitors, they were divided into two groups. Propensity score matching (1:1) was performed to balance the baseline characteristics of the two groups. The baseline characteristics and adverse events between the two groups were compared using the chi-squared test. The survival curves of overall survival (OS) and progression-free survival (PFS) were plotted by the Kaplan-Meier method and differences were analyzed by the log-rank test.The primary endpoints were OS and PFS. Results: As a result, 448 patients were analyzed in this study. 264 patients received PD-L1 inhibitors plus EP and 184 received PD-1 inhibitors plus EP. The median follow-up was 17.6 months. The median OS and PFS was 20.4 months and 7.8 months in the overall population. Before propensity score matching, the median OS was 20.1 months in PD-L1 inhibitor plus EP group and 20.7 months in PD-1 inhibitor plus EP group, respectively (HR 1.043, 95%CI 0.776-1.401; p= 0.781). The median PFS was 7.6 months in the PD-L1 inhibitor plus EP group and 8.5 months in PD-1 inhibitor plus EP group (HR 1.099, 95%CI 0.886-1.364; p= 0.390). After propensity score matching, the median OS and PFS were 20.4 months and 7.8months in PD-L1 inhibitor plus EP group, and those were 20.1 months and 8.6 months in PD-1 inhibitor plus EP group. There was no significant difference in OS and PFS between PD-L1 inhibitors plus EP and PD-1 inhibitors plus EP in the matched population (HR 1.104; p= 0.578 and HR 1.072; p= 0.602, respectively). The overall adverse events were comparable in the two groups. Only ≥3 grade neutropenia was more frequent in the PD-L1 inhibitors plus EP group (77.7% vs 69.0%, p= 0.040). Conclusions: In conclusion, the overall efficacy and safety profile was similar between PD-L1 inhibitors and PD-1 inhibitors for the first-line treatment of ES-SCLC.

ObjectiveTo evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive...

We conducted a meta-analysis to estimate the impact of different clinical and molecular characteristics on the efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors. PubMed and Web of Science were searched for related trials. Eleven eligible studies, comprising 5,663 patients, were included in this meta-analysis. We found that the PD-1/PD-L1 inhibitor was associated with a 31% reduction in the risk of death (hazard ratio [HR]=0.69; 95% CI 0.64–0.74; P<0.00001) for patients with melanoma, non-small-cell lung cancer (NSCLC), urothelial carcinoma, head and neck carcinoma, and renal cell carcinoma. In subgroup analyses, all the patients with PD-L1-positive tumors had overall survival (OS) benefits from PD-1/PD-L1 inhibitors regardless of PD-L1 expression level, and a dose–effect relationship between the expression of PD-L1 and OS benefit from PD-1/PD-L1 inhibitors was observed. There was an OS improvement for patients with a smoking history (P<0.00001), but no OS benefit was observed for nonsmokers (P=0.28). In addition, first-line therapy had better OS than second-line or later treatment (P=0.02). No significant improvement of OS was observed (P=0.70) in patients aged ≥75 years. The relative treatment efficacy was similar according to sex (male vs female, P=0.60), performance status (0 vs ≥1, P=0.68), tumor histology (squamous NSCLC vs non-squamous NSCLC vs melanoma vs urothelial carcinoma vs head and neck carcinoma vs renal cell carcinoma, P=0.64), and treatment type (PD-1 inhibitor vs PD-L1 inhibitor, P=0.36). In conclusion, PD-L1-positive tumors, smoking history, and first-line treatment were potential factors for the efficacy of PD-1/PD-L1 inhibitors. Patients with higher PD-L1 expression might achieve greater OS benefits. In addition, sex, performance status, tumor histology, and treatment type could not predict the efficacy of this therapy. In contrast, patients aged >75 years and nonsmokers might not get OS benefits from this treatment. These results may improve treatment strategies and patient selection for PD-1/PD-L1 inhibitors.

Although the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor combined with chemotherapy vs. chemotherapy alone has been analyzed, there have been no in-depth studies on the outcomes of patients with PD-L1 positive advanced gastric or gastro-esophageal junction cancer patients (GC/GEJC). This systematic review and meta-analysis focused on comparing the efficacy and safety of PD-1/PD-L1 inhibitors vs. PD-1/PD-L1 inhibitors combined with chemotherapy vs. chemotherapy in PD-L1 positive advanced GC/GEJC patients, aiming to provide more precise guidance for the clinical treatment of GC/GEJC. In this meta-analysis, PubMed, Embase, and Cochrane Library were searched from the establishment of the database till June 2022. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy and experimental group patients underwent PD-1/PD-L1 inhibitors or PD-1/PD-L1 inhibitors combined with chemotherapy were included in this investigation. Investigations without complete information, studies from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. The pooled results suggested that chemotherapy combined with immunotherapy prolonged overall survival (OS) in patients with advanced GC/GEJC, while progression free-survival (PFS) with PD-1/PD-L1 inhibitors alone or in combination with chemotherapy were all improved compared with chemotherapy alone. However, PD-1/PD-L1 inhibitors did not significantly increase objective response rates (ORR) in PD-L1-positive patients compared with chemotherapy, but in combination with chemotherapy, they did improve ORR. The pooled results also showed that patients treated with PD-1/PD-L1 inhibitors had higher stable disease (SD) and progressive disease (PD) rates compared to chemotherapy in PD-L1-positive patients. Additionally, in PD-L1-positive patients, PD-1/PD-L1 inhibitors alone or combined with chemotherapy increased OS compared with chemotherapy alone. However, PD-1/PD-L1 inhibitors only prolonged PFS compared with chemotherapy alone in patients with a combined positive score (CPS; 100% of cells were required to be positively stained) for PD-L1, but when combined with chemotherapy, OS and PFS were prolonged in all PD-L1-positive patients compared with chemotherapy alone. Finally, the pooled results showed that the incidence of adverse events of PD-1/PD-L1 inhibitors in PD-L1-zpositive patients was significantly lower than that in patients treated with chemotherapy alone. In conclusion, single agent of PD-1/PD-L1 inhibitor alone or combined with chemotherapy significantly prolongs the survival of patients compared with chemotherapy alone, with fewer adverse effects. However, the degree of CPS may affect efficacy, thus further investigation is required.

BackgroundProgrammed death-1 (PD-1) and programmed death- ligand 1 (PD-L1) inhibitors, such as pembrolizumab, nivolumab and atezolizumab, are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, their use is associated with adverse cardiovascular events. We examined the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors.MethodsPatients receiving PD-1 or PD-L1 inhibitors since their launch up to 31st December 2019 at publicly funded hospitals of Hong Kong, China, without pre-existing cardiac complications were included. The primary outcome was a composite of incident heart failure, acute myocardial infarction, atrial fibrillation, or atrial flutter with the last follow-up date of 31st December 2020. Propensity score matching between PD-L1 inhibitor use and PD-1 inhibitor use with a 1:2 ratio for patient demographics, past comorbidities and non-PD-1/PD-L1 medications was performed with nearest neighbour search strategy (0.1 caliper). Univariable and multivariable Cox regression analysis models were conducted. Competing risks models and multiple propensity matching approaches were considered for sensitivity analysis.ResultsA total of 1959 patients were included. Over a median follow-up of 247 days (interquartile range [IQR]: 72-506), 320 (incidence rate [IR]: 16.31%) patients met the primary outcome after PD-1/PD-L1 treatment: 244 (IR: 12.57%) with heart failure, 38 (IR: 1.93%) with acute myocardial infarction, 54 (IR: 2.75%) with atrial fibrillation, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with lower risks of the composite outcome both before (hazard ratio [HR]: 0.32, 95% CI: [0.18-0.59], P value=0.0002) and after matching (HR: 0.34, 95% CI: [0.18-0.65], P value=0.001), and lower all-cause mortality risks before matching (HR: 0.77, 95% CI: [0.64-0.93], P value=0.0078) and after matching (HR: 0.80, 95% CI: [0.65-1.00], P value=0.0463). Patients who developed cardiac complications had shorter average readmission intervals and a higher number of hospitalizations after treatment with PD-1/PD-L1 inhibitors in both the unmatched and matched cohorts (P value<0.0001). Multivariable Cox regression models, competing risk analysis with cause-specific and subdistribution hazard models, and multiple propensity approaches confirmed these observations.ConclusionsCompared with PD-1 treatment, PD-L1 treatment was significantly associated with lower risk of new onset cardiac complications and all-cause mortality both before and after propensity score matching.

Lung cancer is the main cause of cancer death in the world, with small-cell lung cancer (SCLC) accounting for about 10-15% of all lung cancers. Although programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors represent a major breakthrough in SCLC treatment, only a minority of patients will benefit and there is still a lack of accurate biomarkers to guide clinical application. Inflammation plays a crucial role in tumorigenesis, tumor development, metastasis, and drug resistance, but there is limited research on the predictive value of these inflammatory indicators in SCLC. The purpose of our study was to determine the influence of prognostic nutritional index (PNI), systemic immune inflammation (SII), and other indexes on the efficacy and prognosis of patients with SCLC treated with PD-1/PD-L1 inhibitors. A total of 700 patients of SCLC treated with PD-1/PD-L1 inhibitors in the Fourth Hospital of Hebei Medical University from January 2019 to January 2023 were retrospectively analysed. Among these patients, 246 were included after the inclusion and exclusion criteria were applied. The basic clinical data of patients were collected, included age, sex, PD-1 or PD-L1 inhibitors and so on. The neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR), PNI, SII, and monocyte:lymphocyte ratio (MLR) were calculated. SPSS 27 software was employed for statistical analysis. As of 1st March 2023, all patients had received a post-diagnosis follow-up. The median follow-up time was 11.7 months. Among the 246 patients with SCLC receiving PD-1/PD-L1 inhibitor treatment. the overall response rate and disease control rate were 47.6% and 89.8%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 9.0 months and 21.4 months, respectively. Multivariate analysis showed that MLR [hazard ratio (HR) =0.631; P=0.01], and platelet (PLT) count (HR =1.641; P=0.009) were independent risk factors for PFS. NLR (HR =0.566, P=0.01) and lactate dehydrogenase (LDH) (HR =0.446; P=0.002) were independent risk factors for OS. Among patients with SCLC treated with PD-1/PD-L1 inhibitors, those with high MLR and low PLT had shorter PFS, whilst patients with high NLR and LDH had a shorter OS. NLR and LDH may be used as prognostic biomarkers patients with SCLC treated with PD-1/PD-L1 inhibitors. The promising clinical application of NLR and LDH in efficacy prognostic indicators and beneficiary selection for SCLC immunotherapy is highlighted.

The blockers of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway have achieved great clinical success. However, the limited efficacy and low tumor response rate of anti-PD-1/PD-L1 monotherapy limit the clinical application of PD-1/PD-L1 inhibitors. V-domain immunoglobulin suppressor of T-cell activation (VISTA), a novel checkpoint regulator, exhibits potential synergy with PD-1/PD-L1 in enhancing antitumor immunity. Herein, we report the discovery of benzo[d]oxazole B3 as novel dual small-molecule inhibitors targeting PD-1/PD-L1 and VISTA with high PD-1/PD-L1 inhibitory activity and VISTA binding affinity. B3 rescues the immunosuppression of T-cells mediated by PD-L1 and VISTA and activates antitumor immunity effectively. Moreover, B3 could induce degradation of PD-L1 and VISTA in tumor cell. Furthermore, B3 displays significant in vivo antitumor efficacy in a CT26 mouse model. Our results discover B3 as a promising dual PD-1/PD-L1 and VISTA inhibitor, providing a novel therapeutic strategy to overcome the limitations of current anti-PD-1/PD-L1 therapy.

The clinical efficacy and safety differences between PD-L1 inhibitors and PD-1 inhibitors remain controversial for ES-SCLC. We conduct the retrospective study and propensity score-matched analysis to explore the potential differences between them. This retrospective study analyzed 736 ES-SCLC patients from three centers treated with EP plus either a PD-L1 or PD-1 inhibitor. According to PD-L1 or PD-1 inhibitors, they were divided into two groups. Propensity score matching (PSM, 1:1) was performed to balance the baseline characteristics of the two groups. The primary endpoints were OS and PFS. As a result, 485 patients received PD-L1 inhibitors plus EP and 251 received PD-1 inhibitors plus EP. Before PSM, the PD-1 inhibitor group showed a significantly longer PFS (8.26 vs. 7.44 months; HR 1.252, p = 0.007), but no significant OS difference (20.30 vs. 18.85 months; p = 0.337). After PSM, both median OS (22.43 vs. 20.69 months) and PFS (8.23 months for both) were comparable, with no statistical differences (OS: HR 0.938, p = 0.613; PFS: HR 1.008, p = 0.940). Safety profiles were similar between groups. In conclusion, the overall efficacy and safety profile were similar between PD-L1 inhibitors and PD-1 inhibitors for the first-line treatment of ES-SCLC.

Hyperprogressive disease (HPD) is a new pattern of progression recently described in patients with cancer treated with programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors. The rate and outcome of HPD in advanced non-small cell lung cancer (NSCLC) are unknown. To investigate whether HPD is observed in patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors compared with single-agent chemotherapy and whether there is an association between treatment and HPD. In this multicenter retrospective study that included patients treated between August 4, 2011, and April 5, 2017, the setting was pretreated patients with advanced NSCLC who received PD-1/PD-L1 inhibitors (8 institutions) or single-agent chemotherapy (4 institutions) in France. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) on at least 2 computed tomographic scans before treatment and 1 computed tomographic scan during treatment was required. The tumor growth rate (TGR) before and during treatment and variation per month (ΔTGR) were calculated. Hyperprogressive disease was defined as disease progression at the first evaluation with ΔTGR exceeding 50%. The primary end point was assessment of the HPD rate in patients treated with IO or chemotherapy. Among 406 eligible patients treated with PD-1/PD-L1 inhibitors (63.8% male), 46.3% (n = 188) were 65 years or older, 72.4% (n = 294) had nonsquamous histology, and 92.9% (n = 377) received a PD-1 inhibitor as monotherapy in second-line therapy or later. The median follow-up was 12.1 months (95% CI, 10.1-13.8 months), and the median overall survival (OS) was 13.4 months (95% CI, 10.2-17.0 months). Fifty-six patients (13.8%) were classified as having HPD. Pseudoprogression was observed in 4.7% (n = 19) of the population. Hyperprogressive disease was significantly associated with more than 2 metastatic sites before PD-1/PD-L1 inhibitors compared with non-HPD (62.5% [35 of 56] vs 42.6% [149 of 350]; P = .006). Patients experiencing HPD within the first 6 weeks of PD-1/PD-L1 inhibitor treatment had significantly lower OS compared with patients with progressive disease (median OS, 3.4 months [95% CI, 2.8-7.5 months] vs 6.2 months [95% CI, 5.3-7.9 months]; hazard ratio, 2.18 [95% CI, 1.29-3.69]; P = .003). Among 59 eligible patients treated with chemotherapy, 3 (5.1%) were classified as having HPD. Our study suggests that HPD is more common with PD-1/PD-L1 inhibitors compared with chemotherapy in pretreated patients with NSCLC and is also associated with high metastatic burden and poor prognosis in patients treated with PD-1/PD-L1 inhibitors. Additional studies are needed to determine the molecular mechanisms involved in HPD.

Purpose Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway show significant clinical activity across several tumor types. However, a majority of patients do not respond to these agents. Use of biomarker assays to predict response to these agents is an active area of research; however, the predictive value of PD-L1 immunohistochemistry (IHC) assays is largely inconsistent across clinical trials. In this meta-analysis of clinical trials of PD-1/PD-L1–targeted agents, we evaluate the predictive value of a tumor and tumor-infiltrating immune cell PD-L1 IHC assay as a biomarker for objective response to PD-1/PD-L1 inhibitors. Methods We searched databases (PubMed, Medline, ASCO abstracts, European Society for Medical Oncology abstracts, and Scopus) up until December 2016 for clinical trials using PD-1/PD-L1 inhibitors with reported PD-L1 biomarker data. Objective response rates (primary end point) from all phase I to III trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab in advanced solid tumors were collected. Odds ratios (ORs) for response in PD-L1–positive patients compared with PD-L1–negative patients were calculated using the DerSimonian-Laird random effects model to combine trials. We performed meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Forty-one distinct trials with 6,664 patients were identified. PD-L1 expression was predictive of favorable response across all tumor types (OR, 2.26; 95% CI, 1.85 to 2.75; P &lt; .001), with the significantly largest effect observed in non–small-cell lung cancer (OR, 2.51; 95% CI, 1.99 to 3.17; P &lt; .001). A subgroup analysis across all non–small-cell lung cancer trials using nivolumab and Dako clone 28-8 (Dako, Carpinteria, CA) IHC antibody assay yielded a significantly higher objective response rate in patients with tumor PD-L1 expression even at the minimum cutoff value of 1% (OR, 2.17; 95% CI, 1.03 to 4.57). Conclusion Our meta-analysis shows that tumor and tumor-infiltrating immune cell PD-L1 overexpression based on IHC is associated with significantly higher response rates to PD-1/PD-L1 axis inhibitors across a range of malignant solid tumors.

The incidence and relative risk of PD-1/PD-L1 inhibitors-related colitis in non-small cell lung cancer: A meta-analysis of randomized controlled trials

PurposeThis meta-analysis aimed to clarify the risk of headaches caused by programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors.MethodRelevant clinical trials were screened using PubMed. The risk of headache associated with PD-1 or PD-L1 inhibitors was calculated using the mirror principle and PRISMA guidelines.ResultsA total of 33 clinical trials were screened for this comprehensive meta-analysis, yielding nine mirror-pairing groups. The risk of headache with PD-1 or PD-L1 inhibitors was significantly higher than that with placebo (OR = 1.48, 95% CI: [1.06, 2.06], Z = 2.33, P = 0.02) and similar to that with chemotherapy drugs (OR = 1.06, 95% CI: [0.84, 1.34], Z = 0.49, P = 0.62). When PD-1 or PD-L1 inhibitors are combined with other immune-related drugs, the risk of headaches increases to varying degrees. However, when combined with chemotherapy, this risk did not increase significantly (OR = 1.02, 95% CI: [0.78, 1.32], Z = 0.11, P = 0.91). Compared with PD-1, PD-L1 inhibitors were associated with a higher headache risk (OR = 1.39, 95% CI: [0.64, 2.12], Z = 1.51, P = 0.13).ConclusionPD-L1 has a stronger effect on increasing headache risk than PD-1. Similar to the comparison of PD-1 or PD-L1 versus chemotherapy, PD-1 or PD-L1 plus chemotherapy did not significantly increase headache risk.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12935-025-03911-x.