Background: Immunotherapies targeting PD-1 and CTLA-4 are key components of the treatment of metastatic clear cell renal cell carcinoma (mccRCC). However, they have distinct safety profiles and resistance to treatment can occur. We assess soluble TIM-3 (sTIM-3) in the plasma of mccRCC patients as a potential theranostic biomarker, as well as its source and biological significance.
View Article and Find Full Text PDFBackground: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. While the dysregulation of ERV transcription has been linked to immune cell infiltration in various cancers, its relationship with immune checkpoint inhibitor (ICI) response in solid tumors, particularly metastatic clear-cell renal cell carcinoma (ccRCC), remains inadequately explored.
Methods: This study analyzed patients with metastatic ccRCC from two prospective clinical trials, encompassing 181 patients receiving nivolumab in the CheckMate trials (-009 to -010 and -025) and 48 patients treated with the ipilimumab-nivolumab combination in the BIONIKK trial.
Introduction: KEYNOTE-361 evaluated first-line pembrolizumab with and without platinum-based chemotherapy versus chemotherapy alone in advanced or metastatic urothelial carcinoma. The primary end points of progression-free survival (PFS) or overall survival (OS) were not met. Exploratory analysis of efficacy by platinum agent (cisplatin or carboplatin) is reported.
View Article and Find Full Text PDFIntroduction: LIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics.
View Article and Find Full Text PDFBackground: Oncological systemic treatments such as cytotoxic chemotherapy, radiation therapy or treatment with biological response modifiers can alter the quality of life (QoL) of cancer patients.The aim of this study is to assess the effects of cardiologic magnetic and optical stimulation (CMOS) on QoL in patients with advanced cancer receiving systemic treatment. For this purpose, we designed a non-invasive device that can reproduce and dynamically modulate stimulations of the same nature as the biological electromagnetic emissions specific to the body (cardiac).
View Article and Find Full Text PDFPurpose: The three-arm, phase III KEYNOTE-361 study did not meet its dual primary endpoints of progression-free survival (PFS) or overall survival (OS) with first-line pembrolizumab plus chemotherapy versus chemotherapy in advanced urothelial carcinoma. This prespecified exploratory analysis assessed the association of tumor mutational burden (TMB) and PD-L1 combined positive score (CPS) with clinical outcomes.
Patients And Methods: TMB and PD-L1 CPS were determined via whole-exome sequencing and PD-L1 IHC 22C3 pharmDx, respectively.
Castration-resistant metastatic prostate cancer remains lethal and a therapeutic challenge. Current strategies are geared towards the personalization of treatments based on the identification of relevant molecular targets, including genomic alterations involved in tumoral processes. Among these novel targeted therapies, poly-ADP-ribose polymerase inhibitors (PARPi), by blocking the action of enzymes involved in deoxyribonucleic acid (DNA) repair, induce the destruction of cells carrying defects in homologous recombination repair, often associated with alterations in genes involved in this mechanism.
View Article and Find Full Text PDFWhat Is This Summary About?: This is a summary of a paper that describes the results of the SPARTAN and TITAN studies, which looked at whether a treatment called apalutamide can help treat individuals with advanced prostate cancer.The SPARTAN study included 1207 participants with nonmetastatic castration-resistant prostate cancer (or nmCRPC). The TITAN study included 1052 participants with metastatic castration-sensitive prostate cancer (or mCSPC).
View Article and Find Full Text PDFBackground And Objective: Trough abiraterone concentration (ABI C) of 8.4 ng/mL has been identified as an appropriate efficacy threshold in patients treated for metastatic castration-resistant prostate cancer (mCRPC). The aim of the phase II OPTIMABI study was to evaluate the efficacy of pharmacokinetics (PK)-guided dose escalation of abiraterone acetate (AA) in underexposed patients with mCRPC with early tumour progression.
View Article and Find Full Text PDFRadiotherapy (RT) for high-risk localized prostate cancer (HRLPC) can be controversial in the context of increasing detection of suspicious lymph nodes via advanced imaging techniques. The EORTC 22683 trial initially established RT with androgen deprivation therapy (ADT) as the standard of care for HRLPC, but many patients remain uncured. GETUG-AFU-12 showed that addition of docetaxel and estramustine to ADT improved relapse-free survival but not overall survival.
View Article and Find Full Text PDFBackground: Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities.
Objectives: To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6 weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6 months (late MACE).
Introduction: Papillary renal cell carcinoma (pRCC) is a rare and aggressive cancer with no specifically established therapeutic strategy in the metastatic setting. Combinations of tyrosine kinase and immune checkpoint inhibitors (ICI) are a promising option. We aimed to study the immune landscape of metastatic pRCC, and its interactions with angiogenesis pathways, to search for potential therapeutic targets.
View Article and Find Full Text PDFBackground: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.
Methods: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent.
In the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis.
View Article and Find Full Text PDFEur Ann Otorhinolaryngol Head Neck Dis
August 2024
Objective: Analysis of rechallenge with nivolumab as 5th-line therapy for locally and nodally failed laryngeal squamous cell carcinoma following conventional therapeutic modalities: radiotherapy, surgery and chemotherapy.
Observation: A 70-year-old male, with local and nodal progression of laryngeal squamous cell carcinoma after treatment with chemoradiotherapy and surgery, was initially treated for recurrence with carboplatin, 5-fluorouracile (FU) and cetuximab, followed by second-line nivolumab, and then two lines of conventional chemotherapy with paclitaxel and cetuximab followed by carboplatin and cetuximab. He underwent rechallenge with nivolumab in 5th line, achieving 12months' response, ongoing at the time of writing, and 42.
Purpose: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas].
Patients And Methods: Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily.
Purpose: In a previous exploratory study, modeled early longitudinal prostate-specific antigen (PSA) kinetics observed within the 100-first treatment days with androgen deprivation therapy with or without docetaxel was associated with progression-free survival (PFS) and overall survival (OS) in patients with prostate cancer with rising PSA levels after primary local therapy. This prognostic value had to be confirmed in different settings. The objectives were to assess PSA kinetics modeling in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with chemotherapy in FIRSTANA trial and to investigate modeled PSA kinetic parameters prognostic/predictive value.
View Article and Find Full Text PDFBackground: Preclinical and early clinical data suggest that the irreversible ErbB family blocker afatinib may be effective in urothelial cancers harbouring ERBB mutations.
Methods: This open-label, phase II, single-arm trial (LUX-Bladder 1, NCT02780687) assessed the efficacy and safety of second-line afatinib 40 mg/d in patients with metastatic urothelial carcinoma with ERBB1-3 alterations. The primary endpoint was 6-month progression-free survival rate (PFS6) (cohort A); other endpoints included ORR, PFS, OS, DCR and safety (cohorts A and B).