Combination Of Pembrolizumab Research Articles

Treatment strategies for advanced and recurrent endometrial cancer using immune checkpoint inhibitors.

Doxorubicin + cisplatin and paclitaxel + carboplatin are standard chemotherapy regimens for endometrial cancer. The development of PD-1 and PDL-1 antibody drugs has led to the use of these agents for endometrial cancer in other countries. The KEYNOTE-775 trial for advanced or recurrent endometrial cancer demonstrated the benefits of pembrolizumab and lenvatinib combination therapy, and the results of this trial led to the approval of its coverage for recurrent cancer by the Japanese health insurance system. Currently, treatment with immune checkpoint inhibitors is transitioning from second-line to first-line therapy. In a global randomized phase III study, the drugs dostarlimab, durvalumab, and atezolizumab, which are not yet approved in Japan, showed better results in the study arms than in the control arm. Additionally, biomarkers have been developed for endometrial cancer, enabling gynecologists to pursue treatment options based on the biomarkers detected for better treatment outcomes. In this article, we review the clinical trials of immune checkpoint inhibitors for advanced or recurrent endometrial cancer.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in the Chinese healthcare system

ObjectiveThe combination of pembrolizumab and chemotherapy has demonstrated notable clinical advantages in improving overall survival than chemotherapy alone for patients with untreated advanced pleural mesothelioma. The purpose of this study was to assess its cost-effectiveness.Materials and methodsA Markov state-transition model was constructed using data from the IND227 phase 3 randomized clinical trial. Utility values for health states were taken from the IND227 trial, and direct medical costs were from the pertinent literature and local pricing data. Outcomes measured included quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). To manage the uncertainty in the model, both probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWSA) were used.ResultsIn the base-case analysis, pembrolizumab plus chemotherapy resulted in an incremental gain of 0.23 QALYs at an additional cost of $18,199.63, resulting in an ICER of $80,557.23/QALY. This was not favorable compared to China’s willingness-to-pay (WTP) threshold of $38,042.49/QALY, with an INHB of −0.25 QALYs and an INMB of $-9,605.00. Subgroup analyses showed ICERs for pembrolizumab plus chemotherapy versus chemotherapy of $33,917.61 and $99,536.73 in non-epithelioid and epithelioid patients, respectively. PSA indicated probabilities of cost-effectiveness for pembrolizumab plus chemotherapy at 0.55%, 69.41%, and 0.14% for the entire population and the non-epithelioid and epithelioid subgroups, respectively.ConclusionIn the Chinese healthcare system, the combination of pembrolizumab and chemotherapy did not prove to be more cost-effective than chemotherapy alone as an initial treatment for untreated advanced pleural mesothelioma, with the exception of patients who have non-epithelioid histology.

Sarcoma: Last Year's Practice Changing Papers.

In 2023 and 2024, a wide variety of new studies have been published in the field of soft tissue sarcomas, representing the enormous heterogeneity of sarcoma histotypes, anatomical location, treatment variability, and biological behavior. This article summarizes the, in our view, seven most important publications in the field that will have an impact on the surgical practice and future treatment strategies of our patients. In the last year, we gained more insight in the genetic background of patients with sarcoma from a large Australian study, which will have an impact on future counseling and screening of our patients. Also, the role of radiotherapy in retroperitoneal liposarcoma became clearer in the combined STRASS-STREXIT study. Radiotherapy for extremity sarcomas can now also be done in a 3-week, hypofractioned manner, which is a major improvement for our patients. Furthermore, more evidence has been presented regarding the improved outcome of patients with retroperitoneal sarcoma when treated in high volume centers. Landmark studies with systemic treatment include the positive trial with nirogacestat in desmoid tumors, which have finally shifted the paradigm of desmoid treatment from surgery to systemic treatment. Also, the results of 2 phase 3 randomized controlled trials recently showed 1) that the combination of doxorubicin with trabectedin significantly improved progression free survival for patients with leiomyosarcoma when compared with doxorubicin alone and 2) that the combination of neoadjuvant pembrolizumab and radiotherapy followed by 1-yr adjuvant pembrolizumab significantly improved disease free survival for patients with primary localized undifferentiated pleomorphic sarcoma/myxofibrosarcoma or dedifferentiated/pleomorphic liposarcoma of the extremities or girdles. Key papers from the last year informs us that management of soft tissues sarcoma is constantly improving, since more data became available to guide us in defining the best treatment strategies.

Evolving Treatment Landscape of Frontline Therapy for Metastatic Urothelial Carcinoma: Current Insights and Future Perspectives.

Cisplatin-based chemotherapy has long been the standard first-line (1L) treatment for metastatic urothelial carcinoma (mUC). However, up to 50% of patients with mUC may be ineligible for cisplatin owing to comorbidities, necessitating alternative primary treatment options. Immune checkpoint inhibitors (ICIs) have emerged as a vital alternative for those unable to receive cisplatin. Nevertheless, the prognosis of advanced UC remains dire and challenges persist in optimizing 1L therapy. Recent medical advancements have redirected attention towards innovative drug combinations for the primary treatment of mUC. The combination of enfortumab vedotin (EV) and pembrolizumab has shown significantly improved overall and progression-free survival rates compared to those with chemotherapy alone. This combination can be used as a 1L treatment for patients with mUC who are cisplatin-ineligible or require alternatives to standard chemotherapy. While platinum-based chemotherapy continues to be essential for many patients, the approval of EV and pembrolizumab as 1L treatments for cisplatin-ineligible patients signifies a major breakthrough in primary cancer care. These therapies offer enhanced outcomes in terms of survival and response rates and highlight the increasing relevance of ICI-containing regimens in frontline cancer care. This review provides an exhaustive overview of the current frontline treatment landscape of mUC and explores new therapeutic strategies, with the aim of facilitating clinical decision-making and guiding therapeutic strategies in patients with mUC.

Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia

IntroductionTreatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and...

Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017.

Therapeutic strategies to engage anti-tumor innate immunity are still underdeveloped. Imprime PGG (imprime), a pathogen-associated molecular pattern (PAMP), through pattern recognition receptors, successfully illicit a broad-based innate immune response in preclinical models against various cancers. We aimed to study safety and efficacy of imprime in combination with pembrolizumab in advanced stage non-small cell lung cancer (NSCLC). We conducted an investigator-initiated, multi-institutional, single-arm, phase Ib/II trial in previously treated, advanced stage NSCLC patients. Primary endpoints were maximum-tolerated dose (MTD) of imprime for the phase Ib, and progression-free survival (PFS) for the phase II study (NCT03003468). All 33 eligible patients were included in the safety analysis. No dose-limiting toxicity was observed and the imprime dose of 4 mg/kg was determined as the MTD. Thirty patients treated at the MTD (phase Ib, 6; phase II, 24) were included in the efficacy analysis. Median length of follow-up was 10.8 months. Confirmed objective response rate was 10% [95% confidence interval (CI): 2-27%], with one complete and two partial responses. Median PFS was 2.6 months (95% CI: 1.4-7.0), and 6- and 12-month PFS rates were 37% and 17%, respectively. Median overall survival (OS) was 11.1 months, and 6- and 12-month OS rates were 75% and 46%. Univariate analysis was performed to assess the impact of age, sex, race, disease-stage, programmed death-ligand 1 (PD-L1) expression levels, and prior immunotherapy on PFS and OS. Of these, prior immunotherapy negatively influenced OS [hazard ratio (HR): 2.95, 95% CI: 1.21-7.24]. Overall, the combination was safe and tolerable. The combination of imprime and pembrolizumab is tolerable but did not improve the outcome of advanced stage NSCLC patients who previously progressed on anti-programmed death 1 (PD-1)/PD-L1 immunotherapies. Further investigation is needed to understand the effects of therapeutic PAMPs to mount a strong innate immune response against cancer.

Phase 1/2 Study of the Aurora Kinase A Inhibitor Alisertib and Pembrolizumab in Refractory, Rb-Deficient Head and Neck Squamous Cell Carcinomas.

Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers. Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase 1) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase 2). The recommended phase 2 alisertib dose was 40 mg which had only the expected toxicity including cytopenia that led to dose reductions in two phase 2 patients at cycles 13 and 16. We saw no objective responses, but the combination led to prolonged stable disease (SD) in several patients, including 2 of 10 phase 1 patients (8 and 27 months). Eight of the 15 HPV-positive patients had SD; four of them (heavily pretreated) for ≥6 months, with median overall and progression-free survival durations of 16.8 and 1.4 months, respectively. In circulating immune cells and plasma patients with SD had markedly higher levels of HLA-DR-expressing natural killer cells than did progressive disease patients who demonstrated a more immunosuppressive and inflammatory profile. Pharmacokinetics did not indicate any significant drug-drug interactions between pembrolizumab and alisertib. The combination of alisertib and pembrolizumab was well tolerated and led to prolonged SD in some immunotherapy-resistant patients, supporting our hypothesis that Aurora kinase A inhibition can reverse immunotherapy resistance of retinoblastoma protein-deficient HNSCC.

Quantification of normal bone and osseous metastases in castration-resistant prostate cancer using SPECT/CT with xSPECT Quant: prospective imaging sub-study of a phase 2 clinical trial investigating the combination of pembrolizumab plus radium-223 compared to radium-223 alone.

The purpose of this study is to demonstrate the consistency and reproducibility of quantitative SPECT/CT by evaluating the maximum SUV (SUVmax) in normal bone, to provide the reference value of metastatic lesions, and to evaluate the clinical implication of SUVmax changes of osseous metastasis during treatment. This prospective imaging sub-study was performed as part of a phase 2 clinical trial of patients with metastatic castration-resistant prostate cancer (mCRPC) randomized to the combination of pembrolizumab plus radium-223 or to radium-223 alone (NCT03093428). The maximum standardized uptake value (SUVmax) and mean Hounsfield Unit (HUmean) of normal bone as well as metastases were measured using a 1.5cm region of interest (ROI) on CT and xSPECT Quant reconstruction on the baseline study (S0) and restaging scans. The most tracer-avid metastatic lesion in each patient on S0 was selected as a target lesion, and changes of SUVmax and HUmean of the target lesion were compared on the first restaging scan (S1). Correlations between the percentage changes of SUVmax of the target lesion with alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were assessed. Twenty-one patients were enrolled on the imaging sub-study of which 15 had paired baseline S0 and S1 data. On S0, the median SUVmax and HUmean of normal bone was 5.85g/mL (0.42-14.98) and 133.03 (range, 28.47-461.91), respectively. The median SUVmax and HUmean of metastasis were 42.2g/mL (range, 17.96-143.36) and 549.58 (177.87-1107.64), respectively. There was significant reduction in SUVmax (- 40.1%, range - 86.2 to + 23.5%), p < 0.001) and increase in HUmean (+ 8.3%, range - 11.3 to + 61.7%, p = 0.0479, Wilcoxon signed-rank test) of target lesions between S0 and S1. Spearman correlation between the percentage changes of SUVmax of a target lesion and both serum PSA (r = 0.33, p = 0.226) and ALP (r = 0.45, p = 0.094) were not statistically significant. Quantitative SPECT/CT provides consistent and objective imaging parameters, which can help monitor tumor burden. The median SUVmax of metastasis at baseline was roughly 7.2-fold higher than normal bone. Quantitative SPECT/CT may help visualize the early osteoblastic treatment response in prostate cancer patients treated with radium-223 alone or combined with pembrolizumab.

Recurrence-free patient who underwent surgery after pembrolizumab combination chemotherapy for locally advanced pulmonary pleomorphic carcinoma with high PD-L1 expression

Recurrence-free patient who underwent surgery after pembrolizumab combination chemotherapy for locally advanced pulmonary pleomorphic carcinoma with high PD-L1 expression

The combination of lenvatinib and pembrolizumab in the treatment of patients with metastatic kidney cancer and factors of poor prognosis: experience of clinics in Moscow: A prospective observational study

Background. Combination therapy is the standard of care for intermediate and poor prognosis metastatic renal cell carcinoma. In the IMDC prognostic classification, tumor stage and histological type are not considered due to the lack of independent impact on overall survival. The CLEAR study demonstrated the efficacy of lenvatinib and pembrolizumab combination in long-term treatment outcomes, including overall survival in poor prognosis compared to sunitinib. The KEYNOTE-B61 study demonstrated high efficacy of this combination in patients with non-clear cell renal cell carcinoma. Aim. To evaluate the efficacy of the combination of lenvatinib and pembrolizumab in patients with high tumor burden and non-clear cell histotypes. Materials and methods. This prospective observational study included 54 patients with metastatic renal cell carcinoma who received a combination of lenvatinib and pemrolizumab in the first line between 2022 and May 2024 in oncology clinics of the Moscow Department of Health. Clear cell histotype was represented in 79.6% of cases, 14.8% had papillary cancer, and 5.6% of patients had chromophobe cancer. The primary endpoint was the objective response rate. Results. The objective response was assessed in 50 patients. The objective response rate was 38%, including 2% complete response according to RECIST 1.1, disease progression was in 8% of patients. The median depth of response was -25% (from -100% to +28). The median time to response was 12.4 weeks (1.1–38.3). Conclusion. The efficacy of the combination of lenvatinib and pembrolizumab in real-life clinical practice outside the inclusion criteria of the CLEAR study is clinically significant and allows us to expect improvement even in patients with a large volume of metastatic process and non-clear cell histotype, but the expected benefit in patients with unsatisfactory somatic status remains disputed.

CTIM-31. PRELIMINARY RESULTS OF A PHASE II STUDY OF STEREOTACTIC RADIOSURGERY IN CONJUNCTION WITH THE PD-1 INHIBITOR PEMBROLIZUMAB FOR THE TREATMENT OF RECURRENT HIGH-GRADE MENINGIOMA

Abstract Recurrence of higher-grade meningioma after initial resection and radiotherapy is frequent and associated with high rates of morbidity and mortality. Salvage therapies have limited efficacy and average survival after recurrence is approximately 5-10 years. We report here preliminary data from a phase 2 study combining immunotherapy with checkpoint inhibition with stereotactic radiosurgery for treatment of recurrent high-grade meningioma (NCT04659811). Adult patients with either grade 2 or 3 meningioma who have recurred despite treatment with surgery and radiation and who meet eligibility criteria received stereotactic radiosurgery, in 1 to 5 fractions, in conjunction with pembrolizumab 200mg on the first day of radiation and then every 3 weeks until progression, unacceptable toxicity or for 2 years. Primary objective is PFS12, and secondary objectives include safety of the combined treatment in recurrent meningioma, mOS, mPFS, and neurocognitive function and QOL metrics. To date we have enrolled 18 of planned 37 patients, 33% female, 39% grade 2 and 61% grade 3. Safety lead in was completed without any dose limiting toxicity. There have been 4 SAEs, only one of which was related to study treatment (cerebral edema). 29% of patients had at least one AE, the most common were GI disorders (23%), skin disorders (23%) and headache (17%). Preliminary data from 12 patients shows PFS12 to be 50%, which suggests that the combination of stereotactic radiosurgery may be more beneficial than treatment of Pembrolizumab alone (mPFS 7.6 months). One patient was found to have a homozygous focal deletion of the MLH1 gene and had a dramatic reduction in size of her meningioma with a durable response for over one year. These preliminary data suggest that the combination of stereotactic radiosurgery and pembrolizumab is safe, well tolerated and may be beneficial to patients with recurrent higher-grade meningioma.

Delayed and immediate cutaneous adverse events during pembrolizumab combination chemotherapy against cervical cancer: Case series.

Immune checkpoint inhibitors (ICIs), such as pembrolizumab (PEM), are widely recognized for their antitumor efficacy, but they can also lead to various cutaneous adverse events (CAEs). While most CAEs can be managed with topical corticosteroids, severe cases may necessitate halting immunotherapy. The incidence of severe CAEs is notably higher in combination therapies involving ICIs than in monotherapies, emphasizing the need for stringent, long-term management strategies. This includes potential modifications or discontinuations of the combination therapy. PEM, when added to the conventional paclitaxel + cisplatin (or carboplatin) ± bevacizumab regimen, has shown significant improvements in overall and progression-free survival for patients with Stage IVB metastatic or locally uncontrolled recurrent cervical cancer. This case series retrospectively examined the incidence and management of CAEs in 19 female patients treated with this combination therapy between October 2022 and May 2023. Four patients exhibiting CTCAE grade 3 were identified. The four cases of severe CAEs involved erythema multiforme after the initial course of PEM combination chemotherapy. Notably, three patients experienced immediate hypersensitivity reactions, including anaphylaxis, during subsequent treatments. This observation underscores the necessity for rigorous dermatological monitoring of patients undergoing PEM combination chemotherapy. Such vigilance is crucial for early detection of adverse reactions and timely adjustment of treatment regimens, thereby enhancing patient safety.

The long-term clinical efficacy and safety of lenvatinib plus pembrolizumab in endometrial cancer: data from routine clinical practice in Russia

Background. Endometrial cancer (EC) treatment outcomes need to be improved. Immunotargeted therapy lead to long-term and delayed effects compared to chemotherapy. Estimation of long-term efficacy and quality of life are crucial when we are talking about efficacy in whole.Aim. To evaluate the long-term clinical efficacy of lenvatinib plus pembrolizumab therapy in patients with EC.Materials and methods. The study included 43 patients with stages I-IV EC with mismatch repair-proficient tumors and treatment duration of more than 9 months. We evaluated median progression-free survival, objective response, duration of treatment depending on the line of therapy, prevalence and type of adverse events, and correction regimens. Results. Lenvatinib plus pembrolizumab treatment was safe and efficacious in recurrent EC. Median of progression-free survival (patients with response or stabilization more than 9 months) is 10.2 months (95 % confidence interval 9.1-13.0), median of follow up is 9.7 (1.4-33.8) months. There were no complete responses, partial response was in 12 (28 %) patients, disease stabilization was in 31 (72 %) patients. Regarding safety, the overall rate of any-grade adverse events was 56.3 %. The most common treatment-related adverse events were fatigue (32.6 %), hypertension (23.3 %), and hypothyroidism (18.6 %). Dose reduction was performed in 22 (51.2 %) patients.Conclusion. The combination of lenvatinib plus pembrolizumab has long-term efficacy and manageable profile of safety. The presence of a significant pool of patients with durable response allows improving the survival rate of such patients in Russia.

Efficacy and safety of lenvatinib and pembrolizumab as first-line treatment for advanced renal cell carcinoma patients: real-world experience in Japan.

Combined treatment with lenvatinib and pembrolizumab is currently regarded as one of the standard first-line therapies for advanced renal cell carcinoma (aRCC) patients. The objective of this study was to assess the efficacy and safety of this combined regimen in treatment-naïve Japanese aRCC patients. This study included a total of 50 consecutive aRCC patients receiving combined lenvatinib plus pembrolizumab in routine clinical practice in Japan, and comprehensively analyzed clinical outcomes of this treatment. Of these 50, 7 (14.0%), 23 (46.0%) and 20 (40.0%) were classified into favorable, intermediate and poor risk groups, respectively, according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) system. Responses to this combined therapy in the 50 patients were as follows: complete response, 7 (14.0%); partial response, 26 (52.0%); stable disease, 15 (30%) and progressive disease, 2 (4%); thus, the objective response rate (ORR) was 66%. ORRs in favorable, intermediate and poor risk groups were 57.1, 69.6 and 65.0%, respectively. During the observation period, disease progression and death occurred in 14 (28.0%) and 6 (12.0%) patients, respectively, and neither the median PFS nor OS was reached. Adverse events and those corresponding to grade ≥ 3 were observed in all (100%) and 33 (66.0%) patients, respectively. To our knowledge, this is the first study focusing on real-world outcomes of lenvatinib and pembrolizumab for treatment-naïve aRCC patients, showing that the efficacy and safety of this combined regimen are similar to those noted in randomized clinical trial.

Slow progression of type 1 diabetes associated with pembrolizumab and lenvatinib combination therapy in a patient with probable slowly progressive type 1 diabetes mellitus and endometrial cancer

Slow progression of type 1 diabetes associated with pembrolizumab and lenvatinib combination therapy in a patient with probable slowly progressive type 1 diabetes mellitus and endometrial cancer

A Narrative Review of the Clinical, Humanistic, and Economic Value of Pembrolizumab-Based Immunotherapy for the Treatment of Breast and Gynecologic Cancers.

Breast and gynecologic cancers are common across the world and are associated with substantial societal and economic burden. Pembrolizumab was among the first immune checkpoint inhibitors targeting programmed cell death protein1 to be approved for the treatment of patients with triple-negative breast cancer, cervical cancer, and endometrial cancer. Recent clinical trials have established pembrolizumab regimens as a standard of care treatment for these tumor types. Clinical data are further supported by patient-reported outcome, cost-effectiveness, and real-world evidence. Pembrolizumab monotherapy and combination regimens do not negatively influence health-related quality of life and are cost-effective relative to comparators. Ongoing phase3 studies with pembrolizumab will expand the current understanding of its use in breast and gynecologic cancers. Several of these studies are in patients with early-stage disease with the hope of curing patients. The main objective of this review is to summarize the clinical, humanistic, and economic value of pembrolizumab in these settings and to describe the future challenges for patients, caregivers, clinicians, and payers.

Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1-Positive NSCLC: A Phase II Trial (EAST ENERGY).

Angiogenesis inhibitors are known to modify tumor immunity. Combination of angiogenesis inhibitors with immune checkpoint inhibitors has shown efficacy against many types of cancers, including non-small cell lung cancer (NSCLC). We investigated the feasibility of neoadjuvant therapy with pembrolizumab and ramucirumab, a VEGFR-2 antagonist for patients with PD-L1-positive NSCLC, and its influence on the tumor microenvironment. Patients with pathologically proven, PD-L1-positive, clinical stage IB to IIIA NSCLC were eligible. Patients received two cycles of pembrolizumab (200 mg/body) and ramucirumab (10 mg/kg) every 3 weeks. Surgery was scheduled 4 to 8 weeks after the last dose. The primary endpoint was the major pathologic response rate by a blinded independent pathologic review. The sample size was 24 patients. Exploratory endpoints were evaluated to elucidate the effects of neoadjuvant therapy on the tumor microenvironment. The 24 eligible patients were enrolled between July 2019 and April 2022. The major pathologic response rate was 50.0% (90% confidence interval, 31.9%-68.1%). Six patients showed pathologic complete response. Grade 3 adverse events (AE) occurred in nine patients (37.5%), including three immune-related AEs (acute tubulointerstitial nephritis in two cases and polymyalgia rheumatica in one case). There were no grade 4 or 5 AEs. The transcriptome and multiplex IHC results suggested that tumors with greater CD8+ T-cell infiltration and higher expression of effector molecules at the baseline could show better sensitivity to treatment. This new neoadjuvant combination of pembrolizumab plus ramucirumab was feasible, and anti-VEGF agents may enhance the effects of immune checkpoint inhibitors.

Histology-Specific Clinical Trial of Lenvatinib and Pembrolizumab in Patients with Sarcoma.

Survival of patients with metastatic sarcoma remains poor, and there is a pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multireceptor tyrosine kinase inhibitor targeting tumor vasculature, has an immunomodulatory activity that contributes to its antitumor effects. Therefore, we hypothesized that a combination of lenvatinib and pembrolizumab would lead to improved clinical outcomes in patients with sarcoma. This was an open-label, single-arm study of lenvatinib and pembrolizumab in the following cohorts: (A) leiomyosarcoma, (B) undifferentiated pleomorphic sarcoma (UPS), (C) vascular sarcomas (angiosarcoma and epithelioid hemangioendothelioma), (D) synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST), and (E) bone sarcomas (osteosarcoma and chondrosarcoma). The primary endpoint was the best overall response (BOR) rate documented by RECIST v1.1 by 27 weeks in each cohort, with a threshold of ≥2 responses among 10 patients. Secondary endpoints included progression-free survival, overall survival, duration of response, and safety. Forty-six patients were evaluable for the primary endpoint, which was met in the UPS and MPNST/synovial cohorts (BOR rates by 27 weeks of 25% and 30%, respectively). There were seven partial responses overall with additional responses noted in angiosarcoma and osteosarcoma. Treatment-related adverse events of any grade and grade 3 or higher occurred in 50/51 (98%) and 29/51 (57%) of patients, respectively. We observed durable responses in MPNST, synovial sarcoma, and osteosarcoma. Patients with UPS and angiosarcoma also responded. Further exploration of this approach is warranted to confirm activity and determine optimal dosing schedules.

Viral pneumonia in a patient treated with pembrolizumab - similarity with immune-related pneumonitis.

Immunotherapy is one of the fundamental treatment modalities, especially in the treatment of metastatic non-small cell lung carcinoma, but it is also applied in neoadjuvant, or adjuvant therapy. A certain limitation continues to be immune-mediated toxicity and the broad clinical spectrum of its manifestations, which can present considerable differential diagnostic challenges. We present a case of a female patient who has been treated at our institute since February 2023 for metastatic squamous cell carcinoma of the right lung with first-line systemic therapy of pembrolizumab in initial combination with carboplatin and paclitaxel. Reassessment after four cycles of treatment showed a significant regression of the oncological finding, but also partial fibrotic changes in both lungs. The patient was completely asymptomatic and after consultation with her, it was decided to continue the treatment, now with pembrolizumab monotherapy. Several days after administration, the patient developed resting dyspnea, cough, and fevers. She consulted this deterioration of her condition only at the next scheduled appointment. Persistent dyspnea raised suspicion of immune-mediated pneumonitis. CT of the chest showed significant involvement of all lung lobes and treatment with corticosteroids and antibiotics was initiated. Through bronchoalveolar lavage, positivity for rhinovirus and enterovirus was detected. Viral pneumonia was assessed as the most likely cause of the clinical finding. The established corticosteroid treatment was gradually reduced and after discussion with the patient, we continued the administration of pembrolizumab. A follow-up CT of the lungs showed both further significant regression of the tumor and significant regression of inflammatory changes. Currently, the patient is after a total of 14 cycles of chemo/immunotherapy (of which 9 cycles of pembrolizumab after re-initiation), clinically in excellent condition, while a significant therapeutic response continues. Our case report emphasizes the need for a broader differential diagnosis in the event of pulmonary complications during the administration of immunotherapy. Correct diagnosis of these complications can, among other things, fundamentally affect oncological treatment.

BRAF mutant PD-L1 positive metastatic musculoskeletal lesions from primary lung adenocarcinoma treated with combination vemurafenib and pembrolizumab: a case report

BackgroundB-Raf mutation positivity, B-Raf mutation positivity occurrence with programmed death ligand 1 overexpression, and musculoskeletal metastasis are singly rare in non-small cell lung cancer, and even rarer is all occurring in one patient.Case presentationA Filipino 63-year-old male had B-Raf mutation positive and programmed death ligand 1 overexpressed symptomatic metastatic musculoskeletal lesions from lung adenocarcinoma treated with a BRAF inhibitor, vemurafenib, in combination with an immune checkpoint inhibitor, pembrolizumab. He exhibited significant reduction in pain and burden of musculoskeletal metastatic lesions.ConclusionAlthough a rare occurrence and known to have a poor prognosis, B-Raf mutation positive programmed death ligand 1 overexpressed lung adenocarcinoma presenting with metastatic musculoskeletal lesions can respond favorably to a combination immune checkpoint inhibitor and BRAF inhibitor medication.