The KEYVIBE program: vibostolimab and pembrolizumab for the treatment of advanced malignancies.

Vibostolimab, a humanized IgG1 monoclonal antibody, blocks the interaction between TIGIT and its ligands, preventing the immunosuppressive effects of TIGIT. The addition of vibostolimab to the PD-1 inhibitor pembrolizumab has shown promising antitumor activity, warranting further exploration of vibostolimab as a potential therapeutic option. The KEYVIBE program consists of nine trials that will evaluate the safety and efficacy of vibostolimab monotherapy and vibostolimab-based combination therapy in advanced solid tumors and hematological malignancies. These studies will also evaluate coformulated immunotherapy addressing issues that occur with the sequential administration of immunotherapy. The KEYVIBE program will provide further insight into the clinical utility of vibostolimab-based therapy across multiple indications and various stages of disease.

The KEYVIBE program consisting of nine trials will evaluate the safety and efficacy of the anti-TIGIT antibody vibostolimab across several tumor types.Trial registration: KEYVIBE-001 (NCT02964013); KEYVIBE-002 (NCT04725188); KEYVIBE-003 (NCT04738487); KEYVIBE-004 (NCT05005442); KEYVIBE-005 (NCT05007106); KEYVIBE-006 (NCT05298423); KEYVIBE-007 (NCT05226598); KEYVIBE-008 (NCT05224141); and KEYVIBE-010 (NCT05665595) (ClinicalTrials.gov).

Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients.

OBJECTIVE: Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI). METHODS: A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262). RESULTS: Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4-20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs). CONCLUSION: ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs.

Adjuvant chemoradiotherapy plus pembrolizumab for locally advanced esophageal squamous cell carcinoma with high risk of recurrence following neoadjuvant chemoradiotherapy: a single-arm phase II study.

BACKGROUND: Adjuvant nivolumab reduces recurrence in patients with locoregional esophageal cancer who had pathological residual disease after neoadjuvant chemoradiotherapy and R0 resection. However, the efficacy of adjuvant anti-PD-1 therapy in patients at higher risk of recurrence remains unclear. METHODS: This phase II trial (ClinicalTrials.gov identifier: NCT03322267) enrolled patients with locally advanced esophageal squamous cell carcinoma (ESCC) received neoadjuvant chemoradiotherapy plus esophagectomy but still had various risk factors for recurrence, such as involved or close margins (≤ 1 mm), extranodal extension of the involved lymph nodes, and the ypN2-3 stage. Patients received adjuvant therapy composed of a course of cisplatin-based chemoradiotherapy and pembrolizumab (200 mg, IV every 3 weeks) for 18 cycles. The primary endpoint was 1-year relapse-free survival (RFS) rate. RESULTS: Twenty-five patients were enrolled. The risk factors were tumor margins of ≤ 1 mm (18 patients), extranodal extension of the involved lymph nodes (9 patients), and the ypN2-3 stage (9 patients). The median follow-up duration was 21.6 months (95% CI: 18.7-33.2). The rate of 1-year RFS was 60.0%. The median duration of RFS and overall survival was 14.3 (95% CI: 9.0-19.5) and 21.6 (95% CI: 0.0-45.5) months, respectively. Treatment-emergent adverse events of any grade and those of ≥ 3 grade occurred in 56% and 8% of all patients receiving cisplatin-based chemoradiotherapy and in 79.2% and 12.5% of those receiving pembrolizumab. CONCLUSIONS: Adjuvant chemoradiotherapy followed by pembrolizumab is feasible and may be associated with improved 1-year RFS rate in patients at high risk of recurrence after trimodality therapy for locally advanced ESCC. Trial registration number ClinicalTrials.gov (No. NCT03322267).

Discrepancy in PD-L1 expression between primary and metastatic tumors in two patients with recurrent cervical cancer.

Introduction: Pembrolizumab is an immunotherapy approved for use in patients with a combined positive score (CPS) greater than one with recurrent cervical cancer. In clinical practice, the CPS score is not typically analyzed in both primary and metastatic specimens. Case descriptions: Case 1A 42-year-old woman with history of an abnormal pap smears who presented with a large pelvic mass with initial biopsy of cervix demonstrating squamous cell carcinoma with negative PDL1 expression and a CPS score of 0. She underwent chemoradiation and presented three months after primary treatment completion with recurrence of squamous cell carcinoma and positive PD-L1 expression with a CPS score of 20. Pembrolizumab was added to cycle three of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She had progression on this regimen and was transitioned to tisotumab vedotin; however, ultimately opted to proceed with hospice secondary to failure to thrive.Case 2A 36-year-old woman with history of an abnormal pap smear in pregnancy and initial biopsy demonstrating endocervical adenocarcinoma, mucinous type. She underwent open radical hysterectomy, bilateral salpingectomy, bilateral oophorepexy, and bilateral pelvic lymph node dissection with subsequent adjuvant chemoradiation. Her initial pathology demonstrated positive PDL1 expression with CPS score of 15. She presented six months after completion of primary treatment with recurrence of endocervical adenocarcinoma, mucinous type and negative PD-L1 expression with a CPS score of < 1. Regardless of this discrepancy, pembrolizumab was added to cycle five of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She initially demonstrated a mixed response; however, ultimately progressed after eight cycles and was transitioned to tisotumab vedotin. Discussion: To our knowledge, discrepancies in PD-L1 expression in a matched setting between primary and metastatic tumors has only been reported once. This is the first case report describing these inconsistencies. Etiologies of and outcomes related to the discrepant expression of PD-L1 should be further studied.

Turning the tide: pembrolizumab's triumph in adjuvant RCC therapy.

In recent years, kidney cancer has shown an increased worldwide incidence of more than 400 000 novel cases annually. Although more than half of patients are diagnosed at a localised stage, this disease presents a high-risk of relapse after surgery. Thus, there is a need for adjuvant therapy post-resection to reduce cancer recurrence and prolong disease-free and overall survival. Thorough investigation of adjuvant drugs for renal cell carcinoma (RCC) has shown little promise in the last fifty years, with no recorded overall survival benefits. This was the case until pembrolizumab, an immune checkpoint inhibitor, was introduced into the adjuvant RCC space through the KEYNOTE-564 trial. The adjuvant administration of this novel anti-PD-1 drug demonstrated a significant overall survival benefit which has led to an update in the current treatment guidelines of RCC. This substantial change in the standard of care also caused an investigation of possible treatment combinations and an adoption of innovative predictive biomarkers. In this review, we will present the evolution of past adjuvant ICI trials for the treatment of RCC, the implications of pembrolizumab's overall survival benefits and a discussion of future directions concerning new RCC drug trials and liquid biopsy-based biomarkers.

The efficacy and safety of lenvatinib plus pembrolizumab therapy in patients with uterine carcinosarcoma.

Lenvatinib plus pembrolizumab (LP) therapy is currently used in patients with advanced or recurrent endometrial cancer. However, patients with uterine carcinosarcoma (UCS) were not included in the KEYNOTE-775, and the efficacy of LP therapy for patients with UCS in clinical practice remains unclear. We administered LP therapy to five patients with UCS. We aimed to report our clinical experience with LP therapy in these patients and investigate the genomic characteristics of those who responded to LP therapy. We retrospectively reviewed patients with UCS (n = 5) who underwent LP therapy at our hospital from January 2019 to December 2023. Efficacy was assessed using the response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Safety was evaluated in terms of adverse events. The median age was 65 (55-78) years, and the mismatch repair status was proficient in all of the patients. One patient had stage II disease, and four had stage III. The median number of LP therapy courses was 8 (1-35). The overall response rate was 40%. None of the patients experienced adverse events that were grade 3 or higher. The median follow-up duration was 9 (1-26) months, median progression-free survival was 9.1 (0.16 to NA) months, and median overall survival was 10.2 (1.41 to NA) months. LP therapy may be effective for patients with UCS. As this report was based on a limited number of patients, more cases are required to investigate the efficacy of LP therapy in patients with UCS.

Use of combined chemotherapy and immunotherapy improves pulmonary arterial hypertension.

Treatment modalities for pulmonary arterial hypertension (PAH) improve quality of life and walk distance. However, none of these therapies alter the structural/functional pulmonary vascular integrity that results in vascular remodeling. PAH smooth muscle cells share biological characteristics with cancer cells, which may be potential therapeutic targets for PAH. We present a case of a patient with connective tissue disease (CTD)-associated PAH treated on triple therapy who developed metastatic lung adenocarcinoma. While on PAH triple-therapy, she received a combination of carboplatin, pemetrexed, and pembrolizumab. She eventually had a complete pathologic response, no evidence of cancer recurrence, and significant improvement of PAH/overall clinical status. After discontinuation of neoplastic therapy, her clinical status worsened, she eventually passed away, and lung biopsy findings revealed evidence of severe pulmonary smooth muscle cell hypertrophy and pulmonary veno-occlusive disease. This report suggests that combined chemotherapy and immunotherapy may influence the efficacy of PAH therapies and improve clinical status.

Comparative analysis of adverse event risks in breast cancer patients receiving pembrolizumab combined with paclitaxel versus paclitaxel monotherapy: insights from the FAERS database.

Objective: This study aimed to evaluate the risk of adverse events (AEs) in breast cancer patients treated with pembrolizumab combined with paclitaxel versus those receiving pembrolizumab or paclitaxel monotherapy, using the FDA Adverse Event Reporting System (FAERS) database. Methods: Data were extracted from the FAERS database for breast cancer patients treated with pembrolizumab combined with paclitaxel or with pembrolizumab or paclitaxel monotherapy from Q1 2016 to Q2 2023. Disproportionation analysis was performed by calculating the reporting odds ratio (ROR) with corresponding 95% confidence interval (95% CI), the information component (IC), and the lower bound of the information component 95% confidence interval (IC025) to identify potential safety signals. Results: No significant difference in AEs was observed between the combined treatment group and the pembrolizumab monotherapy group. However, the combined treatment group exhibited a substantial increase in AE risk compared to the paclitaxel monotherapy group. The most significant increases in AE risk were adrenal insufficiency (ROR = 189.94, 95% CI 25.41-1419.7, IC = 3.37, IC025 = 1.59), hypophysitis (ROR = 99.46, 95% CI 12.72-777.4, IC = 3.31, IC025 = 1.44), and myocarditis (ROR = 69.5, 95% CI 8.55-565.23, IC = 3.25, IC025 = 1.33). The time-to-event for combined treatment was 35 (34-70) days, for pembrolizumab was 43 (35-90) days, and for paclitaxel was 42 (37-76) days. The combination therapy group demonstrated significantly shorter intervals to the onset of adrenal insufficiency (p = 0.008), myocarditis (p < 0.001), and immune-related enterocolitis (p = 0.009). Conclusion: Analysis of the FAERS database indicates that combination therapy significantly elevates the risk of adrenal insufficiency, myocarditis, hypophysitis, and immune-related enterocolitis compared to paclitaxel monotherapy. These findings provide critical insights for clinicians in predicting and managing potential AEs associated with this treatment regimen.

Updates and emerging trends in the management of immune-related adverse events associated with immune checkpoint inhibitor therapy.

The rapidly expanding class of therapies targeting immune checkpoints for the treatment of various cancers now includes 8 clinically approved agents: a lymphocyte-activation gene 3 (LAG-3) inhibitor (relatlimab), a cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitor (ipilimumab), three programmed cell death protein 1 (PD-1) inhibitors (nivolumab, pembrolizumab and cemiplimab), and three programmed cell death ligand-1 (PD-L1) inhibitors (atezolizumab, durvalumab, and avelumab). Previously, we reviewed the mechanisms of immune-related adverse events (irAEs), strategies for management of irAEs, and highlighted similarities as well as differences amongst clinical guidelines from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC), and European Society for Medical Oncology (ESMO). Herein, we provide an update that includes discussion of changes to these clinical guidelines since our last review, the new LAG-3 targeted agents, emerging patterns of irAEs, and new directions for improved monitoring and treatment of irAEs that could incorporate interdisciplinary pharmacist-led teams, artificial intelligence, and pharmacogenomics.

Lenvatinib plus pembrolizumab for untreated advanced renal cell carcinoma: a systematic review and cost-effectiveness analysis.

Background: Renal cell carcinoma is the most common type of kidney cancer, comprising approximately 85% of all renal malignancies. Patients with advanced renal cell carcinoma are the focus of this National Institute for Health and Care Excellence multiple technology appraisal. A patient's risk of disease progression depends on a number of prognostic risk factors; patients are categorised as having intermediate/poor risk or favourable risk of disease progression. Objectives: The objectives of this multiple technology appraisal were to appraise the clinical effectiveness and cost-effectiveness of lenvatinib plus pembrolizumab versus relevant comparators listed in the final scope issued by the National Institute for Health and Care Excellence: sunitinib, pazopanib, tivozanib, cabozantinib and nivolumab plus ipilimumab. Methods: The assessment group carried out clinical and economic systematic reviews and assessed the clinical and cost-effectiveness evidence submitted by Eisai, Hatfield, Hertfordshire, UK (the manufacturer of lenvatinib) and Merck Sharp & Dohme, Whitehouse Station, NJ, USA (the manufacturer of pembrolizumab). The assessment group carried out fixed-effects network meta-analyses using a Bayesian framework to generate evidence for clinical effectiveness. As convergence issues occurred due to sparse data, random-effects network meta-analysis results were unusable. The assessment group did not develop a de novo economic model, but instead modified the partitioned survival model provided by Merck Sharp & Dohme. Results: The assessment group clinical systematic review identified one relevant randomised controlled trial (CLEAR trial). The CLEAR trial is a good-quality, phase III, multicentre, open-label trial that provided evidence for the efficacy and safety of lenvatinib plus pembrolizumab compared with sunitinib. The assessment group progression-free survival network meta-analysis results for all three risk groups should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons owing to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. The assessment group overall survival network meta-analysis results for the intermediate-/poor-risk subgroup suggested that there was a numerical, but not statistically significant, improvement in the overall survival for patients treated with lenvatinib plus pembrolizumab compared with patients treated with cabozantinib or nivolumab plus ipilimumab. Because of within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption, the assessment group overall survival network meta-analysis results for the favourable-risk subgroup and the all-risk population should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons. Only one cost-effectiveness study was included in the assessment group review of cost-effectiveness evidence. The study was limited to the all-risk population, undertaken from the perspective of the US healthcare system and included comparators that are not recommended by the National Institute for Health and Care Excellence for patients with untreated advanced renal cell carcinoma. Therefore, the extent to which resource use and results are generalisable to the NHS is unclear. The assessment group cost-effectiveness results from the modified partitioned survival model focused on the intermediate-/poor-risk and favourable-risk subgroups. The assessment group cost-effectiveness results, generated using list prices for all drugs, showed that, for all comparisons in the favourable-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated fewer benefits than all other treatments available to NHS patients. For the intermediate-/poor-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated more benefits than treatment with cabozantinib and nivolumab plus ipilimumab. Conclusions: Good-quality clinical effectiveness evidence for the comparison of lenvatinib plus pembrolizumab with sunitinib is available from the CLEAR trial. For most of the assessment group Bayesian hazard ratio network meta-analysis comparisons, it is difficult to reach conclusions due to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. However, the data (clinical effectiveness and cost-effectiveness) used to populate the economic model are relevant to NHS clinical practice and can be used to inform National Institute for Health and Care Excellence decision-making. The assessment group cost-effectiveness results, generated using list prices for all drugs, show that lenvatinib plus pembrolizumab is less cost-effective than all other treatment options. Study registration: This study is registered as PROSPERO CRD4202128587. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis Programme (NIHR award ref: NIHR134985) and is published in full in Health Technology Assessment; Vol. 28, No. 49. See the NIHR Funding and Awards website for further award information.

Renal cell carcinoma is the most common type of kidney cancer. Several drug treatment options are available for NHS patients with advanced or metastatic disease, and the choice of treatment varies depending on a patient's risk of disease progression. A new drug combination, lenvatinib plus pembrolizumab, may soon become available to treat NHS patients. This review explored whether treatment with lenvatinib plus pembrolizumab offered value for money to the NHS. We reviewed the effectiveness of treatment with lenvatinib plus pembrolizumab versus other NHS treatment options. We also estimated the costs and benefits of treatment with lenvatinib plus pembrolizumab versus current NHS treatments for patients with higher and lower risks of disease progression. Compared with current NHS treatments, treatment with lenvatinib plus pembrolizumab may increase the time that people with a higher risk of disease progression (i.e. worsening disease) were alive. However, for patients with a lower risk of disease progression, the available evidence is limited and only shows that treatment with lenvatinib plus pembrolizumab may prolong the time that patients have a stable level of disease. For all patients, compared to all current NHS treatments, treatment with lenvatinib plus pembrolizumab is very expensive. Compared with current NHS treatments for untreated renal cell carcinoma, using published prices (which do not include any discounts that are offered to the NHS), treatment with lenvatinib plus pembrolizumab may not provide good value for money to the NHS.

Pembrolizumab-Related Sclerosing Cholangitis in a Patient With High Microsatellite Instability Gastric Cancer: A Case Report.

Pembrolizumab is widely used to treat various malignant tumors, including gastric cancer; however, it is associated with immune-related adverse events. Among these adverse events, immune-related sclerosing cholangitis (irSC) is a rare type induced by pembrolizumab, and much remains unknown regarding its clinicopathological features and ideal management. Herein, we report the case of a 67-year-old man who received pembrolizumab for postoperative lymph node recurrence of gastric cancer. He developed irSC after the 15th course of pembrolizumab monotherapy, which was diagnosed using radiological imaging and liver biopsy. The patient was successfully treated with prednisolone. Eight months after the onset of irSC, the dose of prednisolone was tapered, and computed tomography revealed that the treatment response to pembrolizumab was maintained with progression-free lymph node metastasis despite not receiving any anticancer treatment. Understanding the characteristic imaging findings and clinicopathological features of irSC is crucial. Further accumulation of cases is necessary to establish the optimal management of irSC and to identify biomarkers that predict its risk.

Successful treatment of trichilemmal carcinoma with distant metastasis using pembrolizumab: a case report and review.

Trichilemmal carcinoma (TC) is a rare, malignant cutaneous adnexal tumor. TC often has nonspecific clinical manifestations and its aggressive nature is frequently overlooked. Metastasis of TC is rarely reported and there is no standard treatment for recurrent or metastatic TC. We report a complicated case of TC arising from the parotid gland with metastasis to cervical lymph nodes. The tumor progressed after multiple surgeries, radiation and chemotherapy. Finally, the patient achieved good response and disease control with pembrolizumab, an immune checkpoint inhibitor targeting programmed cell death protein-1. Currently, the patient has received 19 cycles of pembrolizumab and the disease remains well controlled. This represents the first reported use of immune checkpoint blockade to treat TC.

This paper discusses a rare form of skin cancer called trichilemmal carcinoma (TC) and presents a distant metastasis TC case. The patient was treated with an immunotherapy called pembrolizumab and after 19 courses of treatment, the tumor was significantly reduced and the symptoms were relieved. This case report is the first recorded case study of pembrolizumab for the treatment of TC and provides a new approach to the treatment of challenging malignancies.

Exceptional Response to Pembrolizumab in HER2-Positive Gallbladder Carcinoma with High Tumor Mutational Burden.

PURPOSE: Patients with advanced cholangiocarcinoma, including gallbladder cancer, typically have a poor prognosis owing to limited effective chemotherapy options. The field of genotype-directed therapy in patients with cholangiocarcinoma is advancing. However, limited clinical data are currently available to evaluate the efficacy of molecularly targeted therapy. METHODS: Herein, we report the case of a 67-year-old man diagnosed with human epidermal growth factor receptor-2 (HER2)-positive and tumor mutation burden-high (TMB-H) cholangiocarcinoma. The HER2-positive and TMB-H characteristics were identified using comprehensive genomic profiling after showing resistance to gemcitabine and S-1 therapy. In the absence of clinical trials for HER2-positive cancer at that time, the patient was treated with pembrolizumab, which is used for TMB-H solid tumors in clinical practice. RESULTS: After receiving pembrolizumab, the patient experienced significant shrinkage in the primary tumor and liver metastases. Thus far, the patient has been receiving pembrolizumab for approximately 10 months. CONCLUSION: To our knowledge, this is the first report showing the efficacy of pembrolizumab in a patient with cholangiocarcinoma harboring both HER2-positive and TMB-H.

Pembrolizumab-Associated Bullous Pemphigoid with Laryngeal Involvement.

Pembrolizumab is a monoclonal antibody with increasing use in many malignancies. We describe a case of pembrolizumab-associated bullous pemphigoid (BP) with laryngeal involvement in a 69-year-old male patient. Diagnosis was made after 2 months of symptoms via biopsy of concurrent, easily accessible cutaneous lesions. Pembrolizumab was discontinued and the patient was started on steroids and dupilumab with ultimate resolution of his cutaneous and laryngeal lesions while on immunosuppression. This case report describes the third case of pembrolizumab-associated laryngeal pemphigoid to increase awareness of this rare immune-related adverse effect. Laryngoscope, 2024.

Potential prognostic predictors of treatment with immune checkpoint inhibitors for advanced endometrial cancer.

BACKGROUND: Prognostic predictors of immunotherapy in patients with advanced endometrial cancer remain unclear. The potential role of inflammatory predictors, including pretreatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet scores, was investigated. METHODS: Between August 2018 and December 2023, 35 patients were retrospectively analyzed. Prognostic predictors were compared, and optimal cut-off values that exhibited the greatest discrimination for overall response, disease control, progression-free survival and overall survival were determined. Multivariate analysis was used to assess the prognostic significance of the predictors. RESULTS: The greatest discrimination for overall response, progression-free survival and overall survival included platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet; the areas under the curve were 0.638, 0.649 and 0.641, respectively. The precise cut-off values of neutrophil-to-lymphocyte ratio for progression-free survival and overall survival were 4.92 and 5.40, respectively. The lower neutrophil-to-lymphocyte ratio group had a significantly longer progression-free survival (P = 0.001, median survival; 4.0 months vs. 19 months) and longer overall survival (P = 0.002, median survival; 5.0 months vs. 21 months). Of the risk factors assessed, neutrophil-to-lymphocyte ratio (hazard ratio = 4.409; 95% CI = 1.10-17.64; P = 0.036) and regimen (hazard ratio = 5.559; 95% CI = 1.26-24.49; P = 0.023) were independently correlated with overall survival. CONCLUSION: In patients with advanced endometrial cancer, pretreatment neutrophil-to-lymphocyte ratio may be a prognostic predictor of those who would benefit from immunotherapy.

Real-world overall survival after alternative dosing for pembrolizumab in the treatment of non-small cell lung cancer: A nationwide retrospective cohort study with a non-inferiority primary objective.

BACKGROUND: High and increasing expenses on pembrolizumab ask for more cost-effective and sustainable treatment strategies to improve affordability of healthcare. Therefore, a part of the Dutch hospitals implemented an alternative, partially lower, weight-based dosing protocol for pembrolizumab. This provided the unique opportunity to compare the overall survival (OS) of the alternative pembrolizumab dosing protocol to standard dosing using a nationwide registry in non-small cell lung cancer (NSCLC) patients. METHODS: This is a retrospective cohort study with a non-inferiority primary objective. Forty hospitals in the Dutch Medication Audit and Dutch Lung Cancer Audit treated 1966 patients with NSCLC with first line pembrolizumab (mono- or combination therapy) between Jan 1st 2021, and Mar 31st, 2023. Alternative weight-based pembrolizumab dosing (100/150/200 mg Q3W or 200/300/400 mg Q6W) was administered to 604 patients, and 1362 patients received standard pembrolizumab dosing (200 mg Q3W or 400 mg Q6W). A Cox proportional hazard model with selected covariates was used to compare the OS between alternative and standard dosing protocols. The non-inferiority margin was set at a hazard ratio (HR) of 1.2 for OS. Non-inferiority is established by showing that the upper limit of the 95 % confidence interval (CI) of the HR of OS is smaller or equal to 1.2. RESULTS: Distribution of age (66.7 years +/-9.4), sex (45 % female) and treatment combinations were similar for both groups, comorbidity score was higher in the standard group. Median daily dose in the alternative dosing group was 22 % lower compared to the standard dosing group, 7.14 mg/day (interquartile range (IQR):5.48-8.04 mg/day) vs. 9.15 mg/day (IQR:8.33-9.52 mg/day), respectively. Alternative dosing was non-inferior to standard dosing regarding overall survival (adjusted HR 0.83, 95 %CI:0.69-1.003). CONCLUSION: This large, retrospective real-world analysis supports the hypothesis that the alternative, partially lower pembrolizumab dosing protocol in NSCLC maintains treatment effectiveness while reducing treatment costs.

Evaluation of pembrolizumab plus cisplatin and fluorouracil in radical treatment for patients with T4b esophageal squamous cell carcinoma.

BACKGROUND: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). METHODS: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. RESULTS: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. CONCLUSIONS: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC.

Bronchoscopic Interventional Therapy Combined With Pembrolizumab in the Treatment of Pulmonary Large Cell Neuroendocrine Carcinoma: A Case Report.

This study reports a significant clinical outcome following the use of bronchoscopic interventional therapy combined with pembrolizumab for treating pulmonary large cell neuroendocrine carcinoma (LCNEC), showcasing a novel approach in managing this aggressive cancer.