Keytruda (pembrolizumab) / Merck (MSD) - LARVOL DELTA

Episode 5: Beyond Surgery: The Evolving Landscape of Adjuvant Therapy in Kidney Cancer (Cancer Network) - "...Garmezy spoke about results from the phase 3 KEYNOTE-564 trial (NCT03142334), which led to the FDA approval of pembrolizumab (Keytruda) for high-risk clear cell kidney cancer.1,2 The positive results from this trial are superior to those from others that explored different immunotherapy agents and regimens, none of which demonstrated a similar benefit. It was noted that there are differences in interpretations, heterogeneity in study designs, and patient populations for each trial."

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Safety and preliminary effects of LabVax 3(22)-23 and GM-CSF, with and without pembrolizumab, in patients with labyrinthin-expressing adenocarcinomas (AACR 2025) - "LabVax and GM-CSF, either alone or in combination with pembro, were well tolerated and elicited detectable humoral and cellular immune effects in heavily pretreated patients with Lab-expressing adenocarcinomas. The study is currently accruing patients for Phase II expansion cohorts."

Clinical • Late-breaking abstract • Oncology • CSF2

Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy Compared with Chemotherapy as First-Line Treatment for Advanced PD-L1-Positive Triple-Negative Breast Cancer from a Japanese Healthcare Perspective. (PubMed, Clin Drug Investig) - "The pembrolizumab plus chemotherapy is likely to be a cost-effective option compared with conventional chemotherapy for patients with PD-L1-positive inoperable or metastatic TNBC in a Japanese medical environment from a healthcare system."

HEOR • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Ex vivo pembrolizumab pharmacology for personalized PD-1 inhibitor therapy reveals a critical gap between receptor occupancy and T cell functionality. (PubMed, Int Immunopharmacol) - "We highlight the importance of evaluating T cell functionality alongside PD-1 receptor occupancy. We identified PD-1-induced modulation of phosphorylation of proximal signalling molecules as potential predictors for ICI treatment response in NSCLC. We recommend further development of this immunopharmacological bioassay for personalization of ICI treatment."

IO biomarker • Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • IL2 • PD-1

Chemotherapy-free neoadjuvant pembrolizumab combined with trastuzumab and pertuzumab in HER2-enriched early breast cancer (WSG-KEYRICHED-1): a single-arm, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Although the null hypothesis could not be rejected, the WSG-KEYRICHED-1 trial highlights the potential of a short chemotherapy-free combination of pembrolizumab with dual anti-HER2 therapy, warranting the initiation of randomised trials investigating the immunotherapy without chemotherapy in patients with HER2-enriched breast cancer."

Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Infectious Disease • Nephrology • Novel Coronavirus Disease • Oncology • Solid Tumor • HER-2

Recent advances in gynecologic radiation oncology. (PubMed, Cancer) - "For patients with locally advanced cervical cancer, results from INTERLACE demonstrate that induction chemotherapy is now a viable treatment option, and KEYNOTE A-18 shows promise for the addition of concurrent and maintenance pembrolizumab to chemoradiation...For patients with vulvar cancer, GOG279 demonstrated that addition of multi-agent chemotherapy with intensity modulated radiation therapy resulted in high rates of complete pathologic response, and GROINS-V III is currently investigating the role of chemotherapy and nodal radiation for patients with macrometastases on sentinel lymph node biopsy. This work summarizes the findings of recent landmark trials in endometrial, cervical, and vulvar cancer and their implications for the radiation oncologist."

Journal • Review • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Vulvar Cancer

Evolving dynamics in clinical trials for oral cancer: Trends, treatment modalities, and future directions. (PubMed, Oral Oncol) - "Future research should focus on large-scale, long-term clinical trials to validate the effectiveness of emerging therapies, particularly immunotherapies, and explore combination therapies that integrate immunotherapy with other modalities."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor

Abscopal effects in malignant melanoma treated with radiotherapy and immune checkpoint inhibition: analysis of a large observational multicenter study (ESTRO 2025) - "Mean time between end of ICI and RT was 3.53 ± 5.67 months, ICI agents were Nivolumab (n=25, 53.2%) and Pembrolizumab (n=21, 44.7%). In MM patients progressive under ICI, RT can induce AR, therefore delaying a switch in systemic treatment. AB occurs more frequently with hypofractionated RT regimens and longer time intervals between ICI and RT. Our results are in line with case series reporting an AR rate between 18-52% and serve as reference for designing prospective trials."

Checkpoint inhibition • Clinical • Melanoma • Oncology • Solid Tumor

Cardiac Sequelae in Metastatic Non-Small Cell Lung Cancer treated non-concurrently with Immunotherapy and SBRT (ESTRO 2025) - "Enrolled patients were treated non-concurrently with immunotherapeutic agents (Pembrolizumab, atezolizumab, durvalumamb) based on molecular status of the tumor and SBRT with CyberKnife to a dose of 40Gy in 5 fractions /8 Gy per fraction/ 5 days to the lung lesions with or without any prior chemotherapy. We conclude that patients treated non-concurrently with immune checkpoint inhibitors and SBRT in metastatic NSCLC exhibit proven cardiotoxicity. Consequential changes were noted on electrocardiogram and echocardiogram post treatment and thus are an invaluable tool in predicting early cardiotoxicity and overall survival."

Metastases • Cardiovascular • CNS Disorders • Coronary Artery Disease • Depression • Heart Failure • Lung Adenocarcinoma • Lung Cancer • Myocardial Infarction • Non Small Cell Lung Cancer • Oncology • Psychiatry • Solid Tumor

Predictors of Pneumonitis in Patients Treated with Systemic Therapy and Radiotherapy for Localized Triple Negative or HER2+ Breast Cancer (ESTRO 2025) - "The overall probability of G2P in patients receiving radiotherapy for localized TN or HER2+ breast cancer was low, with a 3.1% incidence of G2P. The rate did not increase with hypofractionated RT, nor with the addition of perioperative pembrolizumab. Adjuvant T-DM1 was associated with a significantly increased risk of G2P."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pneumonia • Solid Tumor • Triple Negative Breast Cancer • HER-2

Phase 1b/II trial of pembrolizumab plus standard radiotherapy with chemotherapy in Squamous Cell Carcinoma of anus (CORINTH): Cohorts safety data (ESTRO 2025) - P1 | "Immune checkpoint inhibition has recently been shown to be effective in the first line metastatic setting in combination with carboplatin and paclitaxel...Material/ CORINTH is a multicentre, single arm, open-label, non-randomised study to evaluate the safety and tolerability of pembrolizumab with standard IMCRT (53.2Gy in 28d), with Mitomycin-C (D1) and Capecitabine (D1-28) in 50 patients aged 18 years or over with locally advanced SCCA and ECOG performance status 0 or 1... Initial findings suggest the introduction of pembrolizumab on Week 5 of IMCRT schedule (Cohort 1) or on Week 1 (Cohort 2) is safe. Recruitment has commenced to the expansion cohort of 38 patients to confirm safety and tolerability of pembrolizumab starting on Day 1 Week 1 of IMCRT schedule. This will provide data on relative efficacy against historical data."

Clinical • P1/2 data • Anal Carcinoma • Diabetes • Mucositis • Oncology • Squamous Cell Carcinoma • Stomatitis

Tolerance of adjuvant radiotherapy after neoadjuvant chemo-immunotherapy for triple-negative breast cancer and impact of the immunotherapy regimen. (ESTRO 2025) - "This study suggests that adjuvant RT can be safely administered to patients receiving pembrolizumab without excessive radiation-induced toxicity. The schedule of adjuvant pembrolizumab administration does not seem to affect radiotherapy toxicity."

Clinical • Breast Cancer • Dermatitis • Dermatology • Gastrointestinal Disorder • Immunology • Oncology • Pneumonia • Solid Tumor • Triple Negative Breast Cancer

Synergy of Immunotherapy and Radiotherapy in Advanced Lung Cancer: Early Efficacy Outcomes and Translational Implications from the START Study. (ESTRO 2025) - "Blood samples were collected at two time points: before ICB treatment and after RT Among 44 pts with advanced NSCLC, pembrolizumab was the most used ICB (70%), followed by nivolumab (18%) and atezolizumab (12%). RT dose, target sites, treatment intent, and timing appear to influence ICB efficacy, potentially improving disease control and survival outcomes. Modulation of circulating immune cells may be key to these effects. Building on these findings, we've designed a prospective study to further investigate the impact of ICB and RT on tumor response and the immune landscape."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

EORTC 2014-HNCG PROLoNg: Pembrolizumab and Radiotherapy for OLigometastatic squamous cell carcinoma of the head and Neck, randomized phase III trial (ESTRO 2025) - P3 | "The EORTC 2014-HNCG PROLoNg (EU Trial 2023-504478-39; NCT05815927) is a randomized, phase III, open label trial that will be launched in 2025 in four countries (Belgium, Italy, Spain, Switzerland) and aims to be the first multicentric, international effort to provide high-level evidence for the combined approach of SABR and immune checkpoint inhibitors for oligometastatic SCCHN under strict quality assurance for radiotherapy."

Clinical • Metastases • P3 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Bladder preservation therapy with systemic therapy only: The near future or science fiction? (ESTRO 2025) - "In BC the efficacy of cisplatin-based NAC has been summarized by the Advanced Bladder Cancer Meta-Analysis Collaboration reporting 13% reduction in risk of death and 5% absolute benefit at 5 years from 45% to 50%...More recently, the combination of enfortumab vedotin (EV) plus the anti-PD1 pembrolizumab has significantly improved the OS (HR 0.47; 95%CI, 0.38 - 0.58; P<0.001); the PFS (HR 0.45; 95%CI, 0.38 - 0.54; P<0.001) and the ORR (67.7% vs. 44.4%; P<0.001) in aUC patients...The NIAGARA trial compared the NAC with or without durvalumab reporting the increase of the pCR from 27.5% to 37.3% as well as of the OS (HR 0.75; 95%CI, 0.59 - 0.93; P=0.01), and of the disease-free survival (DFS; HR 0.68; 95% CI, 0.56 - 0.82; P<0.001)...The HCRN GU16-257 study tested the combination of nivolumab plus NAC in 76 patients with MIBC...As reported in the aUC, the combination of EV + immunotherapy is expected to significantly increase the rate of pCR as well as the DFS and..."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • ERCC2 • FANCC • RB1

Efficacy of radioimmunotherapy in locally advanced and metastatic cutaneous squamous cell carcinoma – first results of the combi-RISC study (ESTRO 2025) - "Material/ We conducted a retrospective analysis of patients with locally advanced and metastatic cSCC who received first-line therapy with aPD-1i (cemiplimab, pembrolizumab) at the University Hospital Magdeburg or the University Hospital Schleswig-Holstein (Campus Lübeck) between September 2018 and August 2024. In our study, we observed a trend towards an improved ORR and mPFS in patients treated with concurrent RT and aPD-1i compared to patients treated with aPD-1i alone or RT prior to aPD-1i. Patients treated with concurrent RT and aPD-1i showed the highest frequency of adverse events, but these were mostly of low severity. These results indicate synergistic effects of RT and aPD-1i."

Clinical • Metastases • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Tailoring systemic treatment in platin-unfit patients: Lessons learnt from the recurrent-metastatic setting (ESTRO 2025) - "Chemotherapy combinations Carboplatin can be used as an alternative for cisplatin, together with fluorouracil as chemotherapy backbone, in combination with cetuximab or with pembrolizumab...Preliminary results from a single arm trial with weekly carboplatin plus paclitaxel and durvalumab in cisplatin ineligible patients with recurrent or metastatic HNSCC showed a high response rate and favourable overall survival...Monotherapies Immune checkpoint inhibitors are well tolerated as single agents, and subgroup analyses and real-world data have shown that fit older patients derive at least similar benefit from pembrolizumab and nivolumab compared to younger patients. Single agent carboplatin, docetaxel, paclitaxel, methotrexate and cetuximab are well tolerated and can induce tumour responses in patients with recurrent or metastatic HNSCC, but overall response rates are low and a survival benefit has not been demonstrated...Geriatric assessment and performance status are..."

Clinical • IO biomarker • Metastases • Cardiovascular • Head and Neck Cancer • Oncology • Otorhinolaryngology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Focus on urological cancer (ESTRO 2025) - "Clinical trials exploring the combination of brachytherapy with immunotherapies such as nivolumab, pembrolizumab, durvalumab and others are ongoing, with preliminary data indicating improved outcomes in patients with advanced prostate cancer (2, 3)...However, based on the results of phase II trials, no statistically significant improvement in oncological outcomes was observed in patients receiving both sipuleucel-T and radiotherapy (5)...Although combining brachytherapy with immunotherapy holds promise, further research is required to optimise treatment regimens, including dose, fractionation, timing, and sequencing. Prospective clinical trials are critical to better understanding the interaction between these modalities."

IO biomarker • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urethral Cancer • Urology

A phase 3 study of pembrolizumab + concurrent chemoradiotherapy for high-risk locally advanced cervical cancer: interim analysis 2 findings (ESTRO 2025) - P3 | "CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m 2 QW plus external beam radiotherapy (EBRT) followed by brachytherapy. Data from the ENGOT-cx11/GOG-3047/KEYNOTE-A18 study support pembrolizumab plus CCRT as the new standard of care for this population, and as an appropriate control arm in future clinical trials."

Metastases • P3 data • P3 data: top line • Cervical Cancer • Endocrine Disorders • Oncology • Solid Tumor

The role of interventional radiotherapy (brachytherapy) in the immunotherapy era: Focus on gynaecological cancers (ESTRO 2025) - P1/2, P2, P3 | "For anti-VEGF antibody bevacizumab effectiveness has been demonstrated in recurrent or stage IVb disease, however, with an increased risk of major morbidities in case radiotherapy has been applied...Among others, anti-PD-1 antibodies pembrolizumab, nivolumab, cemiplimab, and anti-PDL-1 antibodies azetolizumab, avelumab, durvalumab have been with mixed clinical results...Keynote A-18 (NCT04221945) combining pembrolizumab with chemoradiotherapy and brachytherapy was recently published, demonstrating improved survival in the study arm, however not that differing from survival results as obtained in recent chemoradiotherapy trials including brachytherapy (EMBRACE II, NCT03617133). From the afore mentioned we can conclude that through several ongoing activities in preclinical research settings and clinical trials, evidence for effects of radiotherapy (including brachytherapy) in combination with immunotherapy for gynaecological cancers is slowly emerging."

IO biomarker • Cervical Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Adverse events of hepatic function disorder in Japanese patients with radically unresectable or metastatic renal cell carcinoma treated with pembrolizumab plus axitinib: a post-marketing surveillance study. (PubMed, Int J Clin Oncol) - "There were no new safety signals for AEs of hepatic function disorder, and the incidence was consistent with that reported in KEYNOTE-426, in Japanese patients with radically unresectable/metastatic RCC treated with pembrolizumab plus axitinib."

Adverse events • Journal • P4 data • Genito-urinary Cancer • Hepatology • Oncology • Renal Cell Carcinoma • Solid Tumor

KEYNOTE-869: A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer (clinicaltrials.gov) - P1/2 | N=348 | Active, not recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Dec 2026 ➔ Sep 2026 | Trial primary completion date: Dec 2026 ➔ May 2026

Monotherapy • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urology • Urothelial Cancer

A Unique Case of Endobronchial Cancer and Tracheobronchial Amyloidosis (ATS 2025) - "He was diagnosed with localized TBA and stage IIIA SCC (T2aN2M0) and treated with neoadjuvant chemotherapy and immunotherapy (paclitaxel liposome, carboplatin, and pembrolizumab). After the first cycle, a CT scan showed worsening LLL atelectasis, prompting ceftriaxone treatment and therapeutic bronchoscopy with tumor debulking via endoloop ligation, laser and cryotherapy...Patients with negative mediastinum after therapy have better outcomes.In conclusion, this case highlights the importance of a multidisciplinary approach in managing lung SCC with incidental TBA. The combination of chemotherapy, immunotherapy, and interventional bronchoscopy provided symptom relief and partial tumor regression, though continued monitoring and treatment are necessary for disease control."

Clinical • IO biomarker • Amyloidosis • Atrial Fibrillation • Cardiovascular • Cough • Hepatology • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • CDKN2A • FANCD2 • TP53

Pembrolizumab-induced Reactivation of ANCA-associated Vasculitis Presenting With Hemoptysis and Pauci-immune Glomerulonephritis in a Patient With Metastatic Non-small Cell Lung Cancer (ATS 2025) - "He was treated with pulse-dose methylprednisolone, followed by plasma exchange and rituximab infusion...Further immunotherapy was deferred, and the patient was transitioned to cytotoxic chemotherapy with carboplatin/paclitaxel...Notably in our case, the time of onset was unprecedentedly rapid, occurring just 10 days post-initiation in contrast to the average onset of 7 months documented in prior systematic reviews. Our case highlights the critical need for vigilance regarding irAEs in patients with preexisting autoimmune conditions due to the risk of disease reactivation."

Clinical • IO biomarker • Metastases • ANCA Vasculitis • Bronchiectasis • Glomerulonephritis • Hematological Disorders • Lung Cancer • Lupus Nephritis • Nephrology • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Vasculitis • PD-L1

A Rare Case of Pembrolizumab Associated Steven-Johnson-Syndrome/Toxic Epidermal Necrolysis (ATS 2025) - "Abstract: A 63-year-old female with a medical history of tobacco abuse, COPD, non-small cell lung cancer (CPS 5) with metastasis to the brain presented to the hospital with a painful rash 6 weeks after her second cycle of chemotherapy with carboplatin, paclitaxel, and pembrolizumab...She was prescribed prednisone 1 mg/kg daily for irAE...In the hospital, she was started empirically on vancomycin and meropenem...This case is significant as the indications for immune checkpoint inhibitors are expanding, potential side effects may become more common. SJS/TEN is associated with high mortality which makes early diagnosis, withdrawal of offending agents, and prompt treatment with steroids essential."

Clinical • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Respiratory Diseases • Septic Shock • Solid Tumor • Steven-Johnson Syndrome • Tobacco Addiction