Biomedical subjects

Benjamin Besse

Publications and source records attributed to Benjamin Besse.

5 recordsLinked to original sources

PubMed2026

Role of ctDNA Tumor Fraction in Selecting Immunotherapy-Based Regimens in Advanced Non-Small Cell Lung Cancer.

PURPOSE: Immune checkpoint blockers (ICB) have transformed advanced non-small cell lung cancer (aNSCLC) treatment, but identifying patients who benefit from adding chemotherapy remains challenging, especially in PD-L1 ≥ 50%. PD-L1 is an imperfect biomarker, highlighting the need for better selection tools. EXPERIMENTAL DESIGN: Liquid biopsy (LBx) assessment was performed using hybrid capture-based next-generation sequencing of plasma cell-free DNA. LBx data, molecular profile, and clinicopathologic data were collected. The predictive and prognostic values of tumor fraction (TF) were assessed using a deidentified nationwide (US-based) NSCLC clinicogenomic database [Clinico-Genomic Database (CGDB)]. An independent cohort with aNSCLC from Gustave Roussy was used to validate the findings and to study the correlation of circulating tumor DNA (ctDNA) TF and total metabolic tumor volume and its molecular correlates. RESULTS: In the CGDB database (n = 965), elevated ctDNA TF was prognostic for worse outcomes on ICBs and, when ≥5%, predictive of benefit from ICB + chemotherapy [HR for real-world progression-free survival 0.58 (0.41-0.82); P = 0.002]. The 5% cutoff for TF was validated in an independent cohort from Gustave Roussy. In 283 patients with paired PET scans, ctDNA TF correlated with metabolic tumor volume (rho = 0.46; P < 0.001) and was influenced by TP53/RB1 mutations. CONCLUSIONS: ctDNA TF integrates disease burden and biology. Patients with high ctDNA TF derive greater benefit from chemoimmunotherapy, supporting its use as a biomarker to guide treatment intensification.

Humans↗

PubMed2026

Hyperprogression Upon Cemiplimab Alone or With Short Course Chemotherapy in PD-L1 ≥ 50% Non-small Cell Lung Cancer: A Biomarker Guided Multicenter International Phase 2 Trial-HYPERBOLIC Study.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with PD-L1 ≥ 50%; however, up to 30% of patients experience early progression or death, including cases of hyperprogressive disease (HPD). High baseline levels (≥ 30.5%) of circulating CD10- low-density neutrophils (LDNs) have been associated with increased HPD occurrence. Emerging evidence suggests that combining ICI with platinum-based chemotherapy (PCT) may mitigate the risk of HPD. Currently, no prospective studies have addressed HPD prevention in this context. PATIENTS AND METHODS: HYPERBOLIC (NCT07274384) is a phase 2, randomized, open-label, multicenter, international trial evaluating whether adding 3 cycles of PCT to first-line cemiplimab reduces HPD rate in stage IV NSCLC with PD-L1 ≥ 50% and CD10- LDNs (identified by flow cytometry as CD15⁺CD11b⁺ within the PBMC fraction, with immature cells defined by loss of CD10) ≥ 30.5%. Seventy-four patients will be randomized (1:1 ratio) to receive cemiplimab alone or cemiplimab plus 3 PCT cycles, followed by cemiplimab maintenance. Randomization will be stratified by Lung Immune Prognostic Index. The first computed tomography scan at week 7 after treatment start will assess HPD occurrence, defined as RECIST v 1.1. disease progression with a delta tumor growth rate (ΔTGR) ≥ 50% and/or TGR ratio ≥ 2. The primary endpoint will be the combined rate of HPD and early death (death within 12 weeks with no radiological evaluation). Secondary endpoints will be HPD rate according to alternative definitions, overall survival, progression free survival, objective response rate, and safety. An extensive translational research platform will include spatial transcriptomics of tumor tissue, single-cell RNA sequencing of PBMCs, circulating-free DNA and plasma factors profiling, and saliva/stool microbiome genomics and metabolomics, to longitudinally explore tumor-host dynamic interactions during treatment. CONCLUSION: to our knowledge, HYPERBOLIC is the first prospective, biomarker-driven trial investigating early treatment escalation based on HPD risk in PD-L1-high NSCLC.

CD10↗

PubMed2026

Validation of the lung immune prognostic index in extensive-stage small cell lung cancer: Post hoc analysis of the caspian and IMpower133 phase 3 trials.

BACKGROUND: The Lung Immune Prognostic Index (LIPI) is an inflammation-based biomarker associated with outcomes to immunotherapy across several tumor types. Its prognostic value in extensive-stage small-cell lung cancer (ES-SCLC), however, remains insufficiently validated. We aimed to validate the prognostic impact of LIPI in ES-SCLC using data from two phase III trials. METHODS: Patients enrolled in the CASPIAN (NCT03043872) and IMpower133 (NCT02763579) trials were included. LIPI groups were defined as good (dNLR<3 and LDH<ULN), intermediate (dNLR≥3 or LDH≥ULN) and poor (dNLR≥3 and LDH≥ULN). Overall survival (OS) and progression-free survival (PFS) were assessed across LIPI categories and treatment arms. RESULTS: LIPI was available for 1140 patients (Good: 34%, Intermediate: 49%, Poor: 17%), including 708 treated with chemotherapy-immunotherapy and 432 with chemotherapy alone. Poor LIPI was associated with unfavorable characteristics, including lower albumin levels and higher rate of liver metastases. Median OS was 14.6 months (95%CI: 12.4-15.9) for LIPI Good, 10.9 (10.1-11.5) for Intermediate, and 8.4 (7.1-9.3) for Poor (p < 0.0001). In multivariate models adjusted on gender, age, ECOG, treatment arm and metastatic sites, LIPI remained an independent prognostic factor for OS (HR Poor vs. Good: 1.76, 95%CI: 1.45-2.15, p < 0.001) and PFS (HR: 1.59, 95%CI: 1.33-1.90, p < 0.001). Although patients with poor LIPI derived limited benefit from immunotherapy, no significant treatment-LIPI interaction was observed. CONCLUSION: This large post hoc analysis confirms LIPI as a robust and clinically applicable prognostic biomarker in ES-SCLC. Patients with poor LIPI have substantially worse outcomes and limited benefit from immunotherapy, highlighting the need for novel therapeutic strategies in this subgroup.

Humans↗

PubMed2026

NSCLC in Vulnerable and Special Populations: Toward Personalized Care.

NSCLC encompasses a heterogeneous patient population whose clinical needs, biological features, and treatment outcomes differ substantially from those represented in pivotal studies. Adolescents and young adults, women, pregnant patients, individuals with actionable genomic alterations or constitutional pathogenic variants, immunocompromised patients, including those with chronic viral infections, older adults, patients with brain metastases, and survivors with second primary lung cancers remain consistently underrepresented in research programs. This limits the generalizability of current evidence and challenges the delivery of equitable precision oncology. Across these populations, distinct disease biology, differential genomic landscapes, sex- and age-related variations in pharmacology, and complex psychosocial or ethical considerations shape clinical decision-making. Advances in molecular testing and targeted therapies have improved outcomes for some subgroups; however, persistent disparities in diagnostic access, trial eligibility, and supportive care remain major barriers. In parallel, modern systemic agents including brain-penetrant targeted therapies, immunotherapy combinations, and antibody-drug conjugates have broadened therapeutic options, although their safety, effectiveness, and long-term consequences require dedicated evaluation in underrepresented populations. This review synthesizes contemporary evidence from these special NSCLC populations, highlighting shared challenges and unique considerations. We discuss implications for clinical practice, supportive care, survivorship, and research design and outline opportunities to strengthen inclusivity in precision oncology. Addressing longstanding gaps in representation, trial methodology, and structural inequities is essential to ensure that recent therapeutic advances translate into improved outcomes for the full spectrum of patients living with NSCLC.

Humans↗

PubMed2025

Molecular analysis of lung adenocarcinomas from the SAFIR02-Lung cohort reveals new metastasis-associated copy-number alterations including frequent mutant-specific KRAS-allelic imbalance and identifies CDKN2A homozygous deletions as an independent biomarker of poor prognosis.

BACKGROUND: Identifying molecular alterations specific to advanced lung adenocarcinomas could provide insights into tumour progression and dissemination mechanisms. METHOD: We analysed tumour samples, either from locoregional lesions or distant metastases, from patients with advanced lung adenocarcinoma from the SAFIR02-Lung trial by targeted sequencing of 45 cancer genes and comparative genomic hybridisation array and compared them to early tumours samples from The Cancer Genome Atlas. RESULTS: Differences in copy-number alterations frequencies suggest the involvement in tumour progression of LAMB3, TNN/KIAA0040/TNR, KRAS, DAB2, MYC, EPHA3 and VIPR2, and in metastatic dissemination of AREG, ZNF503, PAX8, MMP13, JAM3, and MTURN. Conversely, no meaningful difference was found in pathogenic single-nucleotide variant frequencies, reinforcing the notion that they are early events in tumorigenesis. CDKN2A homozygous deletion was linked to poor clinical outcome in patients with early tumours (overall survival hazard ratio 2.17, 95% CI: 1.43-3.28, corrected p-value = 0.01). Furthermore, we found that KRAS mutant allele specific imbalance, i.e. focal amplification of the mutant allele, is more prevalent in locoregional or distant samples of metastatic patients than in early lesions (8.4%, 13% and 2.8% respectively). This observation was replicated in three public cohorts. Tumours with KRAS mutant allele specific imbalance show specific patterns of co-occurrence and mutual exclusion with alterations in key cancer genes like CDKN2A, TP53, STK11 and NKX2-1, often in a tumour type dependent manner. CONCLUSION: Advanced LUAD tumours exhibit higher copy-number alteration burden, with distinct alterations associated with tumour progression and metastasis. CDKN2A homozygous deletions predict poor prognosis in early disease, while KRAS mutant allele-specific imbalance is enriched in advanced tumours.

Humans↗

Benjamin Besse

Role of ctDNA Tumor Fraction in Selecting Immunotherapy-Based Regimens in Advanced Non-Small Cell Lung Cancer.

Hyperprogression Upon Cemiplimab Alone or With Short Course Chemotherapy in PD-L1 &#x2265; 50% Non-small Cell Lung Cancer: A Biomarker Guided Multicenter International Phase 2 Trial-HYPERBOLIC Study.

Validation of the lung immune prognostic index in extensive-stage small cell lung cancer: Post hoc analysis of the caspian and IMpower133 phase 3 trials.

NSCLC in Vulnerable and Special Populations: Toward Personalized Care.

Molecular analysis of lung adenocarcinomas from the SAFIR02-Lung cohort reveals new metastasis-associated copy-number alterations including frequent mutant-specific KRAS-allelic imbalance and identifies CDKN2A homozygous deletions as an independent biomarker of poor prognosis.

Hyperprogression Upon Cemiplimab Alone or With Short Course Chemotherapy in PD-L1 ≥ 50% Non-small Cell Lung Cancer: A Biomarker Guided Multicenter International Phase 2 Trial-HYPERBOLIC Study.