Efficacy of Immune Checkpoint Inhibitor Therapy in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer

Abstract

Aim: To describe outcomes of patients with RET fusion-positive non-small-cell lung cancer (NSCLC) who received immune checkpoint inhibitor (ICI)-based treatments in the US. Patients & methods: Using de-identified Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic and Guardant Health databases, treatment patterns and outcomes of 69 patients with advanced/metastatic RET fusion-positive NSCLC who received ICI-based treatment were described. Results: Median real-world progression-free survival and overall survival months were 4.2 (95% CI: 1.4–8.4) and 19.1 (6.9–not reached), respectively, among patients in Clinico-Genomic database (n = 17) receiving first-line ICI-based therapy. In the Guardant Health database, progression-free survival was unavailable, and the median overall survival was not reached (n = 29). Conclusion: Outcomes associated with ICI-based treatments in the first-line setting among patients with RET fusion-positive NSCLC are consistent with unselected populations reported in literature.

Precision therapy for RET-altered cancers with RET inhibitors

“…Response to immunotherapy and chemotherapy Like patients with NSCLC harboring ALK or ROS1 rearrangements, RET-rearranged lung cancers can respond to pemetrexed-based doublet chemotherapy with an objective response rate (ORR) of 45% and median progression-free survival (PFS) of 19 months [61]. There is emerging data on the response to immunotherapy in RET-altered cancers [62][63][64]. A study of 74 patients with RET-rearranged lung cancers who were treated with immune checkpoint inhibitors (ICI) either as single-or dual-agent immunotherapy [63] (Table 1) revealed that RET-rearranged lung cancers have low levels of PD-L1 expression and low tumor mutation burden in the majority of patients and poorer responses to immunotherapy.…”

Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma

“…Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, which comprises approximately 40–50% cases of lung adenocarcinoma (LUAD) and 20–30% cases of lung squamous cell carcinoma (LUSC) ( Liu et al, 2021 ; Siegel et al, 2020 ). Despite advances in chemoradiotherapy and targeted therapies, immune checkpoint inhibitors (ICI), including programmed death-ligand 1 (PD-L1), programmed cell death 1 (PD-1), and cytotoxic T lymphocyte antigen-4 (CTLA-4) represent promising advances in the treatment of lung cancer ( Hiley et al, 2016 ; Bhandari et al, 2021 ; Fountzilas et al, 2021 ); however, the clinical response rate of ICIs is only 20%, which can seriously hinder its wider application ( Borghaei et al, 2015 ; Brahmer et al, 2015 ; Reck et al, 2016 ; Rittmeyer et al, 2017 ).…”

Non-Small-Cell Lung Cancer Patients with Coexistence of High PD-L1 Expression and RET Fusion—Which Path Should We Follow? Case Reports and Literature Review

“…Low intracranial activity of available treatment methods, including immunotherapy, poses a significant challenge in treatment of patients with RET gene fusion. Bhandari et al have recently published results of analysis using data from Flatiron Health-Foundation Medicine Clinico-Genomic Database and Guardant Health Database [ 22 ]. In total, 264 patients with RET fusion were identified and 69 of them had received immunotherapy as first- or second-line treatment.…”

“…In total, 264 patients with RET fusion were identified and 69 of them had received immunotherapy as first- or second-line treatment. Median PFS in patients receiving immunotherapy as first-line treatment was 4.2 months (95%CI 1.4–8.4), while mOS—19.1 months (available data for 17 patients included in Clinico-Genomics Database) [ 22 ]. For 12 patients who received chemoimmunotherapy as first-line treatment mPFS was 5.4 months and mOS—19.1 months (6.9-NR); ORR of 70% was noted.…”

“…TMB and PD-L1 expression data were also presented in the study. They were not complete, as they were available only for 10% of the patients, but PD-L1 expression <1% and TMB < 6 mutations per megabase were observed in most of the cases [ 22 ].…”