Prospective evaluation of immunological, molecular-genetic, image-based and microbial analyses to characterize tumor response and control in patients with unresectable stage III NSCLC treated with concurrent chemoradiotherapy followed by consolidation therapy with durvalumab (PRECISION): protocol for a prospective longitudinal biomarker study

Abstract

Background Concurrent platinum-based chemoradiotherapy (CRT) followed by durvalumab maintenance treatment represents the new standard of care in unresectable stage III non-small cell lung cancer (NSCLC). In this prospective hypothesis-generating single-center study, we aim to identify a framework of prognostic and predictive biomarkers by longitudinal characterization of tumor- and patient (host)-related parameters over all phases of multimodal treatment. Methods This study will enroll 40 patients (≥18 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2, with a diagnosis of PD-L1 positive (≥1%), inoperable stage III NSCLC) with an indication for CRT followed by maintenance treatment with durvalumab according to European Medicines Agency (EMA) approval. Comprehensive analysis will include peripheral blood cellular and humoral immunophenotyping and circulating tumor DNA as well as gut/saliva microbiota analyses. Additional morphological analysis with 18 F-FDG-PET/computed tomography (CT) before, 6 weeks, 6 and 12 months after the end of CRT is included. Statistical analysis using multiple testing will be used to examine the impact of different parameters on progression-free survival (PFS) and overall survival (OS) as well as tumor response and response duration. Discussion This protocol describes the methodology of a comprehensive biomarker study in order to identify a framework of prognostic and predictive markers for unresectable stage III NSCLC in a real-world setting. Trial Registration ClinicalTrials.gov identifier (NCT05027165), data registered on August 2021.

Early recovery of leukocyte subsets is associated with progression-free survival in patients with inoperable stage III NSCLC after multimodal treatment: a prospective explorative study

“…If confirmed, the two identified parameters, peripheral CD8+ T-cell counts and IL-6 plasma concentration after treatment, are immediately amenable to clinical practice. A follow-up study is in progress including 40 inoperable stage III NSCLC patients [29].…”

“…The copyright holder for this this version posted November 21, 2023. ; https://doi.org/10.1101/2023.11.16.23298143 doi: medRxiv preprint two identified parameters, peripheral CD8+ T-cell counts and IL-6 plasma concentration after treatment, are immediately amenable to clinical practice. A follow-up study is in progress including 40 inoperable stage III NSCLC patients [29].…”

A retrospective comparative cohort study: concurrent versus consolidative immunotherapy with chemoradiotherapy in EGFR- or ALK-negative unresectable stage III non-small cell lung cancer

“…Moreover, the GEMSTONE-301 trial further demonstrated that both sugemalimab after concurrent chemoradiotherapy and sequential chemoradiotherapy could provide a longer PFS than could placebo ( 14 ). Several studies have demonstrated that consolidative immunotherapy with chemoradiotherapy can effectively improve the survival prognosis of patients with EGFR/ALK-negative stage III unresectable NSCLC ( 15 ). Some studies have also analyzed the efficacy of chemoradiotherapy combined with immunotherapy compared to that of placebo treatment.…”