BACKGROUND: Immune Checkpoint Inhibitors (ICIs) are becoming a new treatment approach for patients with unresectable hepatocellular carcinoma (uHCC). However, the results regarding its efficacy compared with the standard regimen of targeted therapy are not consistent.
OBJECTIVE: Our aim was to conduct a meta-analysis of existing studies to reveal the differences in the efficacy and safety of the two systems of treatment.
METHODS: The related studies were searched in PubMed, Web of Science, the Cochrane Library, and Embase from inception to June 30th, 2022. Data on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and rate of treatment- related adverse events (TrAEs) with their 95% confidence intervals (CI) were pooled and analyzed by Stata 12.0 software.
RESULTS: A total of ten high-quality controlled clinical studies with 5,539 patients with uHCC were included. The hazard ratio (HR) of the OS and PFS were 0.80 (95% CI, 0.74-0.86) and 0.72 (95% CI, 0.58-0.89), respectively. In addition, the odds ratio (OR) of the ORR and DCR were 3.39 (95% CI, 2.75-4.17) and 1.20 (95% CI, 0.84-1.73), respectively. The ORR of ICIs monotherapy, ICIs plus anti-vascular endothelial growth factor (VEGF) and ICIs plus ICIs were 16% (95% CI, 0.13-0.18), 17% (95% CI, 0.10-0.27), and 20% (95% CI, 0.16-0.24), respectively. For all included studies, the OR of the overall TrAEs was 0.51(95% CI, 0.22-1.18), and grade ≥ 3 TrAEs was 0.78 (95% CI, 0.53-1.14).
CONCLUSIONS: ICIs were more effective than targeted drugs concerning survival periods and ORR in patients with uHCC while maintaining a stable safety profile.

UNASSIGNED: Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1 (PD-L1) in peripheral blood, including soluble form (sPD-L1), expression on circulating tumor cells (CTCs PD-L1) and exosomes (exoPD-L1), are minimally invasive and promising markers for patient selection and management, but their prognostic significance remains inconclusive. Here, we performed a meta-analysis for the prognostic value of PD-L1 blood markers in NSCLC patients treated with ICIs.
UNASSIGNED: Eligible studies were obtained by searching PubMed, EMBAS, Web of Science, and Cochrane Library prior to November 30, 2023. The associations between pre-treatment, post-treatment and dynamic changes of blood PD-L1 levels and progression-free survival (PFS)/over survival (OS) were analyzed by estimating hazard ratio (HR) and 95% confidence interval (CI).
UNASSIGNED: A total of 26 studies comprising 1606 patients were included. High pre- or post-treatment sPD-L1 levels were significantly associated with worse PFS (pre-treatment: HR=1.49, 95%CI 1.13-1.95; post-treatment: HR=2.09, 95%CI 1.40-3.12) and OS (pre-treatment: HR=1.83, 95%CI 1.25-2.67; post-treatment: HR=2.60, 95%CI 1.09-6.20, P=0.032). High pre-treatment exoPD-L1 levels predicted a worse PFS (HR=4.24, 95%CI 2.82-6.38, P<0.001). Pre-treatment PD-L1+ CTCs tended to be correlated with prolonged PFS (HR=0.63, 95%CI 0.39-1.02) and OS (HR=0.58, 95%CI 0.36-0.93). Patients with up-regulated exoPD-L1 levels, but not sPD-L1, after ICIs treatment had significantly favorable PFS (HR=0.36, 95%CI 0.23-0.55) and OS (HR=0.24, 95%CI 0.08-0.68).
UNASSIGNED: PD-L1 blood markers, including sPD-L1, CTCs PD-L1 and exoPD-L1, can effectively predict prognosis, and may be potentially utilized for patient selection and treatment management for NSCLC patients receiving ICIs.

BACKGROUND: Programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important immune checkpoint molecules that contribute to tumor immune evasion. However, the main treatment modalities for patients with early and intermediate stage colorectal cancer (CRC) are surgery, and the role of PD-1/PD-L1 inhibitors in these patients is not yet clear. Therefore, this study aims to review the treatment progress of PD-1/PD-L1 inhibitors for early- and intermediate-stage microsatellite high-instability (MSI-H) and stable (MSS) colorectal cancer, in order to provide more options for patients with early- and intermediate-stage colorectal cancer.
METHODS: A scoping review of clinical trial registries ( Clinicaltrials.gov and EU clinical trial registers) and PubMed/Medline database of trials on PD-1/PD-L1 Inhibitors for early and middle-stage MSI-H and MSS CRC was done up to March 2024.
RESULTS: A total of 19 trials related to early to mid-stage MSH-I or MSS CRC were included. Among them, 6 trials are in recruiting status, 3 trials are in active, not recruiting status, 3 trials are completed, 1 trial is terminated, and 1 trial is unknown. Of these, 9 trials involve MSI-H type CRC, and 10 trials involve MSS type CRC. Preclinical phase I/II trials are predominant, with only 3 clinical phase III trials. In trials related to MSI-H type CRC, 4 studies involve PD-1/PD-L1 inhibitors combined with neoadjuvant therapy, and 5 studies involve combination therapy. In trials related to MSS type CRC, 3 studies involve PD-1/PD-L1 inhibitors combined with targeted therapy, 2 studies involve PD-1/PD-L1 inhibitors combined with chemotherapy, 1 study involves PD-1/PD-L1 inhibitor combined immunotherapy, 1 study involves PD-1/PD-L1 inhibitors combined with bacterial therapy, and 3 studies involve PD-1/PD-L1 inhibitors combined with comprehensive therapy. As for primary outcome measures, 4 trials select pathological complete response rates, 3 trials select progression-free survival rate, 3 trials select objective response rate, 3 trials select overall survival rate, 4 trials select disease-free survival rate, 1 trial selects clinical complete response rate, and 1 trial selects percentage of participants with a dose-limiting toxicity.
CONCLUSIONS: For early- and middle-stage MSI-H and MSS CRC, PD-1/PD-L1 inhibitors have shown some therapeutic efficacy, as evidenced by phase I/II studies. However, contemporary trial designs exhibit heterogeneity, with relatively few inclusion criteria, the use of various drug combinations and regimens, and significant variations in reported endpoints. Nevertheless, more double-arm, multicenter, randomized controlled trials are still needed to confirm the efficacy of immunotherapy.

Immune checkpoint molecules, such as programmed cell death 1 (PD‑1) and programmed cell death ligand 1 (PD‑L1), have a critical role in regulating immune responses, including in tumor tissues. Monoclonal antibodies against these molecules, known as immune checkpoint inhibitors (ICIs), have been shown to be effective against a variety of cancers; however, significant patient populations are resistant to such treatment. Clinical studies to date have shown that ICIs are less effective in cancer patients with bone metastases. The effect of anti‑PD‑1/PD‑L1 antibodies on bone metastases, as assessed by the bone metastasis‑specific response classification criteria, was relatively low. In addition, the presence of bone metastases showed a trend toward worse progression‑free survival and overall survival in cancer patients treated with ICIs. To improve the efficacy of ICIs in bone metastases, several combination therapies are under investigation and certain studies have reported better responses. The present review summarizes the current understanding of the effects of anti‑PD‑1/PD‑L1 antibodies on bone metastases based on the reported clinical and preclinical studies.

The morbidity and mortality rates of endometrial cancer (EC) are increasing yearly. Early-stage EC can be effectively treated through surgery or surgery combined with radiotherapy and chemotherapy. Advanced and recurrent EC is treated with chemotherapy and comprehensive treatment; however, the prognosis for patients at this disease stage is poor. Consequently, novel and effective treatment strategies are urgently required for these patients. Breakthrough progress has been made with the use of immunosuppressants in the treatment of EC, which have been included in treatment guidelines. In the present review, the etiology and classification of EC was outlined and the relevant scientific basis for the application of immunosuppressants in advanced and recurrent EC was discussed. The relevant published and ongoing clinical trials are also summarized. As such, the present review aimed to provide a scientific summary of immunotherapy of EC.

The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway plays a crucial role in the immune escape mechanism and growth of cancer cells in endometrial cancer (EC). Clinical trials investigating PD-1/PD-L1 inhibitor have shown promising results in other cancers, but their efficacy in EC still remains uncertain. Therefore, this meta-analysis aims to provide an updated and robust analysis of the effectiveness and safety of PD-1/PDL1 inhibitor as single-agent immunotherapy in EC, focusing on the objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). This meta-analysis utilized STATA version 17 and RevMan version 5.4 software to pool the results of relevant studies. Five studies conducted between 2017 and 2022, comprising a total of 480 EC patients enrolled for PD-1/PD-L1 inhibitor immunotherapy met the inclusion criteria. The pooled proportion of EC patients who achieved ORR through PD-1/PD-L1 inhibitor treatment was 26.0% (95% CI: 16.0-36.0%; p < 0.05). Subgroup analysis based on mismatch repair (MMR) status showed an ORR of 44.0% (95% CI: 38.0-50.0%; p = 0.32) for the deficient mismatch repair (dMMR) group and 8.0% (95% CI: 0.0-16.0%; p = 0.07) for the proficient mismatch repair (pMMR) group. Pooled proportion analysis by DCR demonstrated an odds ratio (OR) of 41.0% (95% CI: 36.0-46.0%, p = 0.83) for patients undergoing PD-1/PD-L1 inhibitor treatment. Subgroup analysis based on MMR status revealed DCR of 54.0% (95% CI: 47.0-62.0%; p = 0.83) for the dMMR group, and 31.0% (95% CI: 25.0-39.0%; p = 0.14) for the pMMR group. The efficacy of PD-1/PD-L1 inhibitors was significantly higher in the dMMR group compared to the pMMR group, in terms of both ORR (OR = 6.30; 95% CI = 3.60-11.03; p < 0.05) and DCR (OR = 2.57; 95% CI = 1.66-3.99; p < 0.05). In terms of safety issues, the pooled proportion of patients experiencing at least one adverse event was 69.0% (95% CI: 65.0-73.0%; p > 0.05), with grade three or higher AEs occurring in 16.0% of cases (95% CI: 12.0-19.0%; p > 0.05). Based on the subgroup analysis of MMR status, PD-1/PD-L1 inhibitor immunotherapy showed significantly better efficacy among dMMR patients. These findings suggest that patients with dMMR status may be more suitable for this treatment approach. However, further research on PD-1/PD-L1 inhibitor immunotherapy strategies is needed to fully explore their potential and improve treatment outcomes in EC.

This systematic literature review examines the current immune checkpoint inhibitors treatment paradigms, treatment gaps and unmet needs for treating SCLC with respect to efficacy, safety, health related quality of life (HRQoL) and cost-effectiveness.
A search strategy was developed and executed using the National Library of Medicine bibliographic database (PubMed), Cochrane Library, Embase and Google Scholar. Data regarding efficacy, safety, cost-effectiveness and HRQoL were extracted and entered in a data extraction sheet created a priori.
A total of 4961 patients were comprised in all the 12 studies combined. All the studies focus on extensive stage SCLC (ES-SCLC) and not limited stage SCLC (LS-SCLC). All studies used an ICI as the intervention arm and chemotherapy as the control arm. A statistically significant increase in overall survival (OS) and progression free survival (PFS) was observed when ICIs were added to chemotherapy, especially atezolizumab and durvalumab. ICIs in SCLC resulted in immune-related toxicities that have been well-documented in prior immunotherapy trials; their addition to cytotoxic chemotherapy did not worsen chemotherapy-related toxicities. Out of 12 studies, only 3 (25%) included measures to assess the impact of immunotherapy on SCLC patients\' HRQoL. Although domain level scores were limited, the addition of ICIs did not seem to worsen symptoms. Two studies conducted a cost-effectiveness analysis of the combination of atezolizumab plus chemotherapy vs. chemotherapy. The addition of atezolizumab to chemotherapy was not found to be cost-effective in either study.
Combining ICIs with chemotherapy enhanced OS and PFS as well as not worsening HRQoL. Among all ICIs, PD-L1 inhibitors showed better effectiveness. Future studies should focus on real-world settings and more clinical trials using ICIs for not only ES-SCLC but also LS-SCLC.

Brain metastases (BMs) indicate poor outcomes and are commonly excluded in immunotherapy clinical trials in advanced lung cancer; moreover, the effect of BM status on immunotherapy efficacy is inconsistent and inconclusive. Therefore, we conducted a meta-analysis to assess the influence of BM status on immunotherapy efficacy in advanced lung cancer.
Electronic databases and all major conference proceedings were searched without language restrictions according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We extracted randomized clinical trials on lung cancer immunotherapy that had available overall survival (OS) and/or progression-free survival (PFS) data based on the BM status. All analyses were performed using random effects models.
Fourteen randomized clinical trials with 9,089 patients were identified. Immunotherapy conferred a survival advantage to BM patients [OS-hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58-0.90; P = 0.004; and PFS-HR, 0.68; 95% CI, 0.52-0.87, P = 0.003]. Non-BM patients could also derive a survival benefit from immunotherapy (OS-HR, 0.76; 95% CI, 0.71-0.80; P <0.001; and PFS-HR, 0.68; 95% CI, 0.56-0.82, P <0.001). The pooled ratios of OS-HRs and PFS-HRs reported in BM patients versus non-BM patients were 0.96 (95% CI, 0.78-1.18; P = 0.72) and 0.97 (95% CI, 0.79-1.20; P = 0.78), respectively, indicating no statistically significant difference between them. Subsequent sensitivity analyses did not alter the results. Subgroup analyses according to tumor type, line of therapy, immunotherapy type, study design, and representation of BM patients reconfirmed these findings.
We demonstrated that BM status did not significantly influence the immunotherapy efficacy in lung cancer, suggesting that both BM and non-BM patients could obtain comparable benefits.
https://www.crd.york.ac.uk/prospero/, identifier (CRD42020207446).

Immune checkpoint blockade with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors has been standard care for metastatic nonsmall cell lung cancer (NSCLC) and after progression using first-line platinum-containing chemotherapy. Although several management guidelines exist for immune checkpoint inhibitor-induced toxicities, uncommon, complicated, and life-threatening immune-related adverse events remain challenging for oncologists. In this report, we presented a male patient with NSCLC who received pembrolizumab during disease progression. He developed interstitial pembrolizumab-induced organizing pneumonia (OP). The patient received 9 months of anti-PD-1 pembrolizumab when he presented with dry cough and fatigue. The patient developed a solitary nodular lung lesion mimicking a newly occurred metastatic lesion in the lung without a significant circulating tumor marker increase. Sputum analysis was negative for acid-fast bacilli and fungi. A computed tomography-guided percutaneous lung biopsy was conducted and showed alveolar fibrous thickness and various lymphocyte infiltration. Immunotherapy-related OP was identified, and he subsequently responded well to corticosteroids. This case describes a clinical situation, where PD-1-induced OP is radiologically similar to NSCLC disease progression in the lungs. Oncologists should be aware of uncommon pulmonary PD-1/PD-L1 inhibitor toxicity. Lung biopsy may help to distinguish immune-related pneumonitis, lung infections, and progressive nodular lesions.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have reported durable responses in selected groups of patients with metastatic urothelial carcinoma (mUC). However, identification of biomarkers predictive of response to ICIs remains an unmet need in mUC management, and the role of programmed cell death ligand 1 (PD-L1) expression remains controversial.
OBJECTIVE: In this systematic review and meta-analysis, we aimed at assessing the predictive value of PD-L1 in mUC patients receiving first-line ICIs as monotherapy or in combination with other anticancer agents across randomized controlled clinical trials (RCTs).
METHODS: We retrieved all the relevant RCTs through PubMed/Medline, Cochrane library, and EMBASE; proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible studies included RCTs evaluating ICIs versus chemotherapy in PD-L1-positive mUCs; the primary endpoint was overall survival (OS).
RESULTS: Three phase III trials matched our eligibility criteria; a total of 2237 PD-L1-positive mUC patients (ICIs: 1125; chemotherapy: 1112) were included in the analysis. Compared with chemotherapy, ICIs were associated with higher OS in PD-L1-positive patients (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.78-0.96; p = 0.007); conversely, no differences were observed in the PD-L1-negative patient population (HR 1.03, 95% CI 0.89-1.19; p < 0.001).
CONCLUSIONS: Compared with standard chemotherapy, our results suggested a survival benefit in PD-L1-positive mUC patients receiving ICIs; conversely, no benefit was observed in patients with PD-L1-negative disease. Although this systematic review and meta-analysis should be interpreted with caution due to several issues, our results highlight the need for reliable predictive biomarkers of response to ICIs, providing a benchmark for future studies in this setting.
UNASSIGNED: Despite immune checkpoint inhibitors (ICIs) having revolutionized the treatment landscape of metastatic urothelial carcinoma (mUC), an important percentage of patients do not experience clinical benefit or durable responses. Identification of reliable biomarkers of response to ICIs remains a mandatory need in mUC management, and further efforts are needed to standardize the assessment of programmed cell death ligand 1 in urothelial carcinoma.