Safety Of Immune Checkpoint Inhibitors Research Articles

Immunotherapy for non-small cell lung cancer in the elderly population: a generic protocol.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness and safety of immune checkpoint inhibitors (ICI) as monotherapy or in combination compared to standard of care for elderly people (≥ 65 years) with non-small cell lung cancer (NSCLC).

Management and treatment of severe immune-related hepatotoxicity based on clinical and pathological characteristics.

The management of severe immune-related hepatotoxicity (irH) needs to be further optimized. This study aims to analyze the clinical characteristics of severe irH; improve the therapeutic strategy, especially salvage treatment in steroid-refractory irH; and determine the safety of immune checkpoint inhibitor (ICPi)-rechallenge. This multicenter retrospective study included patients who developed severe irH and those without irH after immunotherapy between May 2019 and June 2023. Propensity score matching was used to match these two cohorts with similar baseline characteristics. Among 5,326 patients receiving ICPis, 51 patients developed severe irH. irH occurred after a median duration of 36days and a median of two doses after the first ICPi administration. Patients receiving PD-L1 inhibitors faced a lower risk of developing severe irH. A higher dose of glucocorticoids (GCS) was administered to grade 4 irH than grade 3 irH. For steroid-sensitive patients, grade 4 irH individuals received a higher dosage of GCS than those with grade 3 irH, with no difference in time to resolution. Meanwhile, a significantly higher dose of GCS plus immunosuppression was needed in the steroid-refractory group. Liver biopsy of the steroid-refractory patients exhibited heterogeneous histological features. Twelve patients were retreated with ICPi. No irH reoccurred after a median follow-up of 9.3months. irH requires multidimensional evaluation. PD-L1 inhibitors correlated with a lower risk of severe irH. Grade 4 irH demands a higher dose of GCS than recommended. Pathology may guide the salvage treatment for steroid-refractory irH. ICPi rechallenge in severe irH is feasible and safe.

The efficacy of immune checkpoint inhibitors as a part of multimodality treatment in soft tissue and bone sarcoma in an academic community setting.

e23564 Background: Prior studies have shown response to immune checkpoint inhibitors (ICI) in a variety of sarcoma subtypes, however, much is still unknown about ICI use in specific sarcoma subtypes due to disease rarity. Patients (pts) are often treated with these agents as part of clinical trials, and real world data in the community setting is lacking. The aim of this study is to report real world efficacy and safety of ICI in sarcoma either alone or with radiation (RT) and/or surgery. Methods: A retrospective cohort review was conducted to identify pts with soft tissue and bone sarcoma who were administered ICI at Kellogg Cancer Center at NorthShore University HealthSystem/Endeavor Health. Pts who received ICI as part of a clinical trial were excluded. Results: A total of 29 pts receiving ICI were identified. Pts had a median of 1 prior systemic therapy. ICI included pembrolizumab (n = 23), nivolumab (n = 5), and ipilimumab/nivolumab (n = 1). Treatment was discontinued in 28 pts due to disease progression (n = 18), toxicities (n = 3), death (n = 2), and maximal response (n = 5). One patient is still undergoing treatment. Median progression-free survival (PFS) was 4.9 months. Median overall survival (OS) was 14 months. Overall response rate (ORR) is 31%. Median duration of response was not reached (44+ months). Complete response (CR) (n = 5) reported in 3 pts with undifferentiated pleomorphic sarcoma (UPS), 1 pt with SMARCA4 deficient undifferentiated sarcoma, and 1 pt with dedifferentiated chondrosarcoma. Partial response (PR) (n = 4) reported in 1 pt with UPS, 1 pt with dedifferentiated liposarcoma, 1 pt with high grade spindle sarcoma of bone, and 1 pt with malignant peripheral nerve sheath tumor. Of those pts with a CR, 2 patients received only pembrolizumab, 1 pt was administered concomitant RT, and 2 pts had administered concomitant surgery. Of the pts who had PR, 3 were also treated with concomitant RT. Grade 3 immune related adverse effects were reported in 5 of the 29 patients. Of these patients, 2 had documented CR and 3 documented PR. Conclusions: This study expands on the real world efficacy of ICI in a variety of sarcoma subtypes. CR and PR rates in this setting were high, and responses were durable, although selection bias for treatment may have played a role. This data supports the treatment of metastatic sarcoma with ICI, especially with concomitant RT and surgery, in a variety of subtypes.

Efficacy and safety of immune checkpoint inhibitors in advanced solid tumors with hepatitis B infection.

Efficacy and safety of immune checkpoint inhibitors in advanced solid tumors with hepatitis B infection.

Efficacy and safety of immune checkpoint inhibitors in recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis.

e14612 Background: Treatment options for recurrent or metastatic nasopharyngeal carcinoma (NPC) are limited. Recently, the introduction of Immune Checkpoint Inhibitors (ICIs), either as single agents or combined with other treatment options, has emerged as a potential treatment for NPC. Hence, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICIs compared to standard chemotherapy. Methods: We systematically searched PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing ICIs versus standard chemotherapy in patients with NPC. The main outcomes were progression-free survival (PFS), overall survival (OS) and adverse events rate. All analyses used a random-effects model, with 95% confidence intervals (CIs) and were conducted on Review Manager 5.4. Results: A total of 1,188 patients from 5 RCTs were included, of which 634 (53.3%) received PD-1 inhibitors. In a pooled analysis of all studies, treatment with ICIs demonstrated a statistically significant benefit in OS (HR 0.73; 95% CI 0.61-0.87; p<0.01). In trials evaluating ICI monotherapy versus chemotherapy (617 patients), PFS was not significantly different between groups (p=0.91). However, pooling two studies evaluating ICI combined with chemotherapy vs. chemotherapy (541 patients) demonstrated higher PFS for the ICI group (HR 0.53; 95% CI 0.42-0.67; p<0.01). Overall pooled PFS was non-significant (HR 0.75; 95% CI 0.49-1.16; p=0.20). In all subgroup analyses, patients treated with ICI achieved greater PFS than chemotherapy: low EBV DNA level (HR 0.61; 95% CI 0.42-0.87; p=0.007) or high EBV DNA level (HR 0.44; 95% CI 0.35-0.56; p<0.01), without liver metastasis (HR 0.68; 95% CI 0.47-0.98; p=0.04), and with liver metastasis (HR 0.56; 95% CI 0.38-0.83; p=0.04). Moreover, ICIs were well tolerated and not associated with an increased risk of serious adverse events (HR 0.96; 95% CI 0.82-1.11; p=0.56). The frequency of hypothyroidism increased in the ICI group (HR 2.07; 95% CI 1.63-2.63; p<0.01). Other adverse events had similar rates in both groups, such as AST and ALT levels, diarrhea, pruritus, rash, stomatitis, and vomiting. Conclusions: This meta-analysis demonstrated that immune checkpoint inhibitors significantly enhanced overall survival without substantially increasing serious adverse events in patients with M/R NPC. Further studies are needed to identify the patients who benefit the most from ICI monotherapy or combination therapies. [Table: see text]

The later-line efficacy and safety of immune checkpoint inhibitors plus anlotinib in EGFR-mutant patients with EGFR-TKI-resistant NSCLC: a single-center retrospective study

BackgroundEffective treatment after EGFR-TKI resistance is of great clinical concern. We aimed to investigate the efficacy and safety of anlotinib in combination with an anti-PD-1/PD-L1 antibody in later-line therapy for EGFR-mutant NSCLC patients after TKI treatment failure and to explore the independent predictive factors of therapeutic efficacy.MethodsA total of 71 patients with confirmed advanced EGFR-mutated NSCLC who progressed after previous standard EGFR-TKI therapy but still failed after multiline treatments were included retrospectively in this study. Most of the patients had previously received at least three lines of treatment. All were treated with anlotinib combined with anti-PD-1 or anti-PD-L1 therapy. The safety of this combined treatment was assessed by the incidence of adverse events. The efficacy of the regimens was evaluated by survival analysis (OS, PFS, ORR, DCR).ResultsThe median follow-up period was 28.6 months (range: 2.3–54.0 months), and the median number of treatment lines was 4. The overall response rate (ORR) and disease control rate (DCR) were 19.7% and 77.5%, respectively. The median PFS was 5.8 months (95% CI 4.2–7.4 months), and the median OS was 17.1 months (95% CI 12.0–22.3 months). Patients who received immune checkpoint inhibitors plus anlotinib had an encouraging intracranial ORR of 38.5% and a DCR of 80.8%. ECOG performance status < 2 at baseline was independent protective factors of PFS. Metastatic organs and ECOG performance status were independent parameters in predicting OS. Treatment-related adverse events occurred in 66 (93.0%) patients; most of the adverse events were Grade 1–2, and no increase in adverse events was observed compared to monotherapy.ConclusionAnlotinib combined with an anti-PD-1/PD-L1-based regimen exhibited promising efficacy and tolerance in NSCLC patients with EGFR mutations after previous TKI failure. The efficacy of this combined regimen in patients with EGFR mutations should be further evaluated.

Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study

BackgroundImmuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development.MethodsThis retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs.ResultsOur study included 181 patients (median age: 82 years, range: 80–94), mostly men (73%), with a performance status of 0–1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/μL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118.ConclusionIO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study

The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P<0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P<0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P<0.0001; 47.3% vs 29.7%, P<0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Treatment Strategies for Non-Small-Cell Lung Cancer with Comorbid Respiratory Disease; Interstitial Pneumonia, Chronic Obstructive Pulmonary Disease, and Tuberculosis.

Non-small cell lung cancer (NSCLC) patients are often complicated by other respiratory diseases, including interstitial pneumonia (IP), chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB), and the management of which can be problematic. NSCLC patients with IP sometimes develop fatal acute exacerbation induced by pharmacotherapy, and the establishment of a safe treatment strategy is desirable. For advanced NSCLC with IP, carboplatin plus nanoparticle albumin-bound paclitaxel is a relatively safe and effective first-line treatment option. Although the safety of immune checkpoint inhibitors (ICIs) for these populations remains controversial, ICIs have the potential to provide long-term survival. The severity of COPD is an important prognostic factor in NSCLC patients. Although COPD complications do not necessarily limit treatment options, it is important to select drugs with fewer side effects on the heart and blood vessels as well as the lungs. Active TB is complicated by 2-5% of NSCLC cases during their disease course. Since pharmacotherapy, especially ICIs, reportedly induces the development of TB, the possibility of developing TB should always be kept in mind during NSCLC treatment. To date, there is no coherent review article on NSCLC with these pulmonary complications. This review article summarizes the current evidence and discusses future prospects for treatment strategies for NSCLC patients complicated with IP, severe COPD, and TB.

Safety and clinical efficacy of immune checkpoint inhibitors in advanced gastric cancer in the real world.

To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. The results of this paper show that the occurrence of irAEs is associated with patients' OS. irAEs occurrence can prolong patients' OS. irAEs occurrence may serve as a surrogate marker for ICIs.

Clinical outcomes and safety of immune checkpoint inhibitors in patients with solid tumors and paraneoplastic syndromes

BackgroundPatients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce.MethodsIn this retrospective...

Effectiveness and Safety of Immune Checkpoint Inhibitors in Older Cancer Patients.

The development of immunotherapy checkpoint inhibitors (ICIs) has revolutionized cancer care. However, old patients are underrepresented in most clinical trials, although they represent a significant proportion of real-world patients. We aimed to evaluate the effectiveness and safety of ICIs in patients older than the age of 70. We performed a retrospective chart review of 145 patients aged 70 or older treated with ICIs for metastatic or unresectable cancer. Median progression-free survival (PFS) was 10.4 months (95% CI 8.6-13.7), with no differences between octogenarians and septuagenarians (p = 0.41). Female gender (p = 0.04) and first-line treatment setting (p < 0.0001) were associated with a longer median PFS. Median overall survival (OS) was 20.7 months (95% CI 13.5-35.0 months), with no difference based on performance status, cancer site, gender, or between septuagenarians and octogenarians (all p > 0.005). Patients treated with ICIs in the first-line setting reported longer OS compared to treatment in the second-line setting (p < 0.001). Discontinuation of ICIs due to adverse effects was associated with both shorter PFS (p = 0.0005) and OS (p < 0.0001). The effectiveness of ICIs in older cancer patients primarily depends on the line of treatment and treatment discontinuation. Octogenarians experienced similar treatment responses, PFS, OS, and adverse effects compared to septuagenarians.

The Efficacy and Safety of Immune Checkpoint Inhibitors in Adrenocortical Carcinoma: A Systematic Review and Meta-Analysis.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC) remains uncertain. Thus, we conducted a systematic review and meta-analysis to summarize the efficacy and tolerability of ICIs in patients with advanced ACC. We searched PubMed, Scopus, and CENTRAL for studies that used ICIs in ACC. Studies with more than five patients were included in the meta-analysis of the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and grade 3/4 adverse events. Twenty studies with 23 treatment arms and 250 patients were included. Single-agent anti-PD1 or anti-PD-L1 treatment was utilized in 13 treatment arms, whereas an anti-PD1 or anti-PD-L1 and anti-CTLA4 combination was used in 4 treatment arms. Other anti-PD1- or anti-PD-L1-based combinations were used in five treatment arms. The ORR was 14% (95% CI = 10-19%, I2 = 0%), and the DCR was 43% (95% CI = 37-50%, I2 = 13%). The combination anti-PD1- or anti-PD-L1-based treatment strategies did not correlate with higher responses compared with monotherapy. The median OS was 13.9 months (95% CI = 7.85-23.05), and the median PFS was 2.8 months (95% CI = 1.8-5.4). ICIs have a modest efficacy in advanced ACC but a good OS. Further studies are needed to investigate predictive biomarkers for ICI response and to compare ICI-based strategies with the current standard of care.

Comparative safety of immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and network meta-analysis.

To indirectly compare the safety of immune checkpoint inhibitors (ICIs) in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by network meta-analysis (NMA). Through August 1, 2023, we searched PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for randomized clinical trials (RCTs) of ICI-based treatment for R/M HNSCC. Outcomes of interest included overall and organ-specific immune-related adverse events (irAEs). Addis 16.5 software was used to perform NMA. Confidence in Network Meta-Analysis (CINeMA) was used to assess confidence in the evidence. Nine RCTs were included in this NMA, involving a total of 4016 patients. The general safety of ICI-based treatments in descending order was as follows: Durvalumab + Tremelimumab, Camrelizumab + Chemotherapy, Durvalumab, Toripalimab + Chemotherapy, Pembrolizumab, Pembrolizumab + Chemotherapy, Nivolumab, Tremelimumab. There were differences in the toxicity profile among Toripalimab + Chemotherapy (dermatologic irAEs), Camrelizumab + Chemotherapy (hypothyroidism), Nivolumab + Ipilimumab (hyperthyroidism, pneumonitis), Pembrolizumab (nephrotoxicity), Pembrolizumab + Chemotherapy (colitis). ICI-based treatment increased the incidence of endocrine irAEs (hyperthyroidism and hypothyroidism) and pneumonitis compared to conventional therapy. Besides, the combination of dual ICIs resulted in a greater occurrence of irAEs compared to the use of a single ICI. The safety ranking of treatments based on ICIs is significantly influenced by specific irAEs. These irAEs, which vary in type and severity, play a crucial role in determining the overall safety profile of each ICI regimen. PROSPERO CRD42023460267.

The efficacy and safety of immune-checkpoint inhibitors plus chemotherapy versus chemotherapy for non-small cell lung cancer: An updated systematic review and meta-analysis.

Immune-checkpoint inhibitors(ICIs) combined with chemotherapy are emerging as an effective first-line treatment in advanced non-small cell lung cancer (NSCLC); however, reports on the magnitude of effectiveness and safety are conflicting. Relevant articles published before February 2022 were searched in PubMed, Embase, and the Cochrane Library. The study included all randomized controlled trials that evaluated ICIs with chemotherapy versus chemotherapy for the treatment of NSCLC. Among the outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Our meta-analysis included a total of 12 studies. Overall analysis indicated that ICIs plus chemotherapy could significantly improve OS (HR = 0.79; 95% CI: 0.74-0.84; I2 = 44.4%, P = 0.055), PFS (HR = 0.62; 95% CI: 0.59-0.67; I2 = 75.3%, P = 0.000), and ORR (RR = 1.48; 95% CI: 1.27-1.73; I2 = 79.0%, P = 0.000) when compared to chemotherapy treatments. Subgroup analysis showed that PD-1/PD-L1 inhibitors combined with chemotherapy significantly improved OS, PFS, and ORR when compared with chemotherapy with decreased grade 1-2 TRAEs. In addition, female patients with nonsquamous histology might receive more OS benefit from ICIs plus chemotherapy when compared to chemotherapy alone. Despite the fact that CTLA-4 inhibitors combined with chemotherapy increased PFS, there were no benefits gained in OS nor ORR. When PD-L1/CTLA-4 inhibitors were added to chemotherapy, the risk of grade 3-5 adverse events increased whereas PD-1 inhibitors did not. ICIs plus chemotherapy, compared with chemotherapy, were associated with significantly improved PFS, ORR, and OS in NSCLC therapy. However, PD-L1/CTLA-4 inhibitors plus chemotherapy could increase the risk of grade 3-5 adverse events, but not PD-1 inhibitors plus chemotherapy.

Impact of renal function eligibility criteria in clinical trials and real-world survival outcomes among patients with metastatic renal cell carcinoma.

407 Background: Registration trials in metastatic renal cell carcinoma (mRCC) establishing the efficacy of first-line (1L) combination regimens employed strict renal function eligibility criteria (NCT02853331, NCT02811861, NCT03141177, NCT02231749); however, pharmacokinetics and safety of immune checkpoint inhibitors and anti-vascular endothelial growth factor therapies have been shown to be similar regardless of baseline renal function. Therefore, we aim to evaluate the impact of renal function eligibility criteria used in previous trials on real world outcomes. Methods: Data from the US nationwide Flatiron Health electronic health record-derived de-identified database included adult patients (pts) with mRCC who received any 1L systemic treatment on or after 4/16/2018 (first FDA combination regimen approval), had hemoglobin level ≥9 g/dL and ECOG performance status (ECOG) 0-1 at 1L. Renal function eligibility criteria at 1L (-60 days to +7 days) include serum creatinine (≤1.5 vs &gt;1.5 x ULN), eGFR (≥30 vs &lt;30 ml/min/1.73m2) and calculated CrCl (≥40 vs &lt;40 ml/min) based on registration trial protocols. Outcomes include real world progression free survival (rwPFS), time to next treatment (rwTTNT), and overall survival (rwOS) from 1L. Inverse probability of treatment weighted (IPTW) Kaplan Meier methods and Cox proportional hazard models with multiple imputation were applied. Results: Of 2038 pts in this cohort, 1390 (68.2%) met all criteria for renal function (included), 140 (6.9%) met at least one criteria (relaxed), 46 (2.3%) met none (excluded), and 462 (22.7%) had unknown renal function. Compared to included pts, excluded pts were more likely to be older (median age: 74 vs 66), female (35% vs 27%), have recurrent disease (61% vs 53%), less likely to have ECOG 0 (24% vs 40%) and favorable IMDC risk (9% vs 14%). Excluded pts are also more likely to be Non-Latinx Black (13% vs 6%) and have lowest SES quintile (22% vs 15%) compared to included pts. Although, after weighting included pts had higher median rwPFS of 9.3 (95% CI 8.4 - 10.1) vs 6.9 (95% CI 3.7 - 9.9), rwTTNT 12.0 (95% CI 11.0 - 13.1) vs 9.1 (95% CI 5.5 - 16.4) and rwOS 38.5 mo (95% CI 35.9 - 44.5) vs 19.3 mo (95% CI 16.6 - 41.8) compared to relaxed/excluded pts, none of the hazard ratios (HRs) were statistically significant after multiple imputation (Table). Conclusions: In this real world study, we found that although only 68.2% of patients met all renal function eligibility criteria, survival outcomes were not different across pts groups. This suggests that mRCC patients with reduced renal function may benefit similarly to 1L treatment and should not be excluded from clinical trials. [Table: see text]

PEMBROBLAD: Real world effectiveness and safety of immune checkpoint inhibitors in patients with advanced urothelial carcinoma with histological variants.

PEMBROBLAD: Real world effectiveness and safety of immune checkpoint inhibitors in patients with advanced urothelial carcinoma with histological variants.

Efficacy of immunotherapy in patients with non-small cell lung cancer

Introduction. Non-small cell lung cancer (NSCLC) is a form of lung cancer with high incidence and low overall survival. Immunotherapy is a promising treatment method for which the selection of optimal treatment regimens for each individual patient is important.Aim. To evaluate the effectiveness and safety of immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC.Materials and methods. The study included 247 patients (190 men and 57 women) aged 37 to 87 years who received ICIs as monotherapy with nivolumab (n = 58; 23.4%), pembrolizumab (n = 78; 31.6%) and atezolizumab (n = 13; 5.3%), and in the form of combination chemoimmune therapy (n = 98; 39.7%). The objective response of the tumor to treatment was recorded in the presence of partial or complete regression of the tumor. The tumor response to treatment was determined in accordance with the iRECIST criteria.Results. Objective response was achieved in 20.6% of patients, of which 13.7% were on the first line setting, and 7% of patients were on the 2nd or more line setting. Disease control was recorded in 83.3% of patients. Patients receiving combination chemoimmune therapy had a better response to treatment than those receiving monotherapy (χ2 = 9.309; p = 0.020). Grade 3–4 immuno-related adverse events were observed only in 5 (2.02%) patients.Conclusions. NSCLC immunotherapy allows to achieve high rates of objective response and disease control (20.6 and 83.3%, respectively), with a small number of grade 3–4 immuno-related adverse events (2.02% according to our data), which indicates an acceptable safety profile.

Immune checkpoint inhibitor use and the incidence of hepatitis B virus reactivation or immune-related hepatitis in non-small cell lung cancer patients with chronic hepatitis B.

The safety of immune-checkpoint inhibitors (ICIs) has not been thoroughly investigated in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B infection (OBI). The authors analyzed the incidence of hepatitis B virus (HBV) reactivation, immune-related hepatitis and jaundice in NSCLC patients in a real-world setting. A total of 1277 NSCLC patients treated with ICIs were analyzed. Among them, 52 patients were hepatitis B surface antigen (HBsAg) (+) (group A, CHB), 759 patients were HBsAg (-)/hepatitis B core antibody immunoglobulin G (anti-HBc IgG) (+) (group B, OBI), and 466 patients were HBsAg (-)/anti-HBc IgG (-) (group C). Among the 52 patients with CHB, 38 (73.1%) were receiving antiviral therapy. The primary end point was HBV reactivation, immune-related hepatitis, and jaundice. The secondary end points included other immune-related adverse events and efficacy. HBV reactivation was observed in two patients (0.2%) who were both in group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed in 14.3% (2 of 14 patients). The incidences of immune-related hepatitis and jaundice were comparable among the three groups. The incidence of ≥grade 3 other immune-related adverse events and efficacy were all comparable among the three groups (p>.05 for all comparisons). In this large, real-world cohort study, the safety and efficacy of ICIs were comparable in patients with CHB and OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis should be required for them. For patients with OBI, the risk of HBV reactivation was minimal.

Clinical practice guidelines for cervical cancer: the Korean Society of Gynecologic Oncology guidelines.

This fifth revised version of the Korean Society of Gynecologic Oncology practice guidelines for the management of cervical cancer incorporates recent research findings and changes in treatment strategies based on version 4.0 released in 2020. Each key question was developed by focusing on recent notable insights and crucial contemporary issues in the field of cervical cancer. These questions were evaluated for their significance and impact on the current treatment and were finalized through voting by the development committee. The selected key questions were as follows: the efficacy and safety of immune checkpoint inhibitors as first- or second-line treatment for recurrent or metastatic cervical cancer; the oncologic safety of minimally invasive radical hysterectomy in early stage cervical cancer; the efficacy and safety of adjuvant systemic treatment after concurrent chemoradiotherapy in locally advanced cervical cancer; and the oncologic safety of sentinel lymph node mapping compared to pelvic lymph node dissection. The recommendations, directions, and strengths of this guideline were based on systematic reviews and meta-analyses, and were finally confirmed through public hearings and external reviews. In this study, we describe the revised practice guidelines for the management of cervical cancer.