Publications by authors named "Stephen V Liu"

The ADRIATIC study marks a major advancement in limited-stage small cell lung cancer (LS-SCLC), showing that consolidation therapy with durvalumab after chemoradiation significantly improves overall survival (OS) and progression-free survival (PFS). This establishes durvalumab as the new standard of care for LS-SCLC.

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Background: Gene copy number gain (CNG) is a continuous variable. The relevant cutpoint for HER2, KRAS and MET CNG in non-mall cell lung cancer remains uncertain. As de novo driver oncogenes are largely mutually exclusive, oncogene overlap analysis can be used to explore CNG thresholds.

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Fusions in neuregulin 1 () are rare oncogenic drivers that occur across a number of tumor types, including non-small cell lung cancer (NSCLC). has an EGF-like domain that serves as a ligand for HER3 receptors, inducing heterodimerization, usually with HER2, and subsequent activation of oncogenic downstream signaling pathways. Emerging evidence suggests that NSCLC harboring fusions do not respond as well to standard therapeutic options including chemotherapy and immunotherapy, and prognosis is poor.

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Article Synopsis
  • A study evaluated the effectiveness and safety of cabozantinib in combination with atezolizumab compared to cabozantinib alone in patients with advanced non-small cell lung cancer (NSCLC) who had previously received an immune checkpoint inhibitor (ICI).
  • The phase 1b COSMIC-021 trial included stage IV non-squamous NSCLC patients who progressed on an ICI, assessing treatment response and safety profiles for both groups.
  • Results showed a modest objective response rate of 20% for the combination therapy and 6% for the single-agent treatment, with high rates of treatment-related adverse events but manageable toxicity overall.
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  • IMbrella A is a Phase III study that allowed patients from earlier atezolizumab trials, like IMpower133, to continue receiving treatment for extensive-stage small cell lung cancer (SCLC) with atezolizumab plus chemotherapy after the initial trials closed.
  • In IMbrella A, 18 out of 26 eligible patients rolled over for further treatment, and results showed that median follow-up was 59.4 months with estimated three-, four-, and five-year overall survival rates of 16%, 13%, and 12%, respectively.
  • The study reported that 16.7% of patients experienced serious adverse events, with only one grade two hypothyroidism noted,
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Purpose: Anti-PD-1/PD(L)1-based combination therapy is the standard of care in first line (1L) for metastatic nonsquamous non-small cell lung cancer (mnsqNSCLC) without driver alterations. This study aimed to evaluate real-world clinical outcomes in this population.

Methods: Eligible physicians in the United States, Europe, and Japan abstracted information from medical charts of eligible adult patients with mnsqNSCLC (without /, no known alterations) who initiated 1L anti-PD(L)1-based combination therapy for mnsqNSCLC between 2017 and 2021.

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Objectives: MET exon 14 skipping alterations (METex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of METex14+ NSCLC.

Materials And Methods: NSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences.

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Purpose: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, natural killer cells and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies.

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Introduction: With multiple targeted therapies approved for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), it is increasingly important to understand outcomes with various sequences of next-generation ALK tyrosine kinase inhibitors (TKIs). We describe contemporary sequencing patterns and treatment effectiveness of first-line (1L) and second-line (2L) treatments in patients who received second-generation ALK TKIs in the 1L treatment of ALK-positive NSCLC in the United States.

Methods: A cohort of adults with ALK-positive advanced NSCLC who initiated treatment with 1L alectinib or brigatinib between June 2017 and April 2021 in the Flatiron Health electronic health record-derived de-identified database were followed through April 2023.

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Introduction: Characteristics of long-term survivors in EGFR-mutant (EGFRm) NSCLC are not fully understood. This retrospective analysis evaluated a multi-institution cohort of patients with EGFRm NSCLC treated in the pre-osimertinib era and sought to describe characteristics of long-term survivors.

Methods: Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with EGFRm metastatic NSCLC who started first-line therapy before 2015.

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Background: TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach.

Methods: Breast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ).

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Article Synopsis
  • Activating point mutations in the MET tyrosine kinase domain are identified as oncogenic drivers in various cancers, occurring in about 0.5% of cases, particularly in certain papillary renal cell carcinomas.
  • Specific mutations at positions H1094, L1195, F1200, D1228, Y1230, and M1250 were labeled as oncogenic or likely oncogenic based on genetic profiling.
  • Preclinical models and patient responses indicate that these mutations may enhance sensitivity to MET inhibitors, highlighting the potential for targeted precision treatments in oncology.
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Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 or its ligand (PD-1/L1) have expanded the treatment landscape against cancers but are effective in only a subset of patients. Tumor mutation burden (TMB) is postulated to be a generic determinant of ICI-dependent tumor rejection. Here we describe the association between TMB and survival outcomes among microsatellite-stable cancers in a real-world clinicogenomic cohort consisting of 70,698 patients distributed across 27 histologies.

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Purpose: To characterize treatment patterns and real-world clinical outcomes of patients with metastatic non-small cell lung cancer (mNSCLC) who developed progression on an anti-PD-1/anti-PD-L1, herein referred to as anti-PD-(L)1, and platinum-doublet chemotherapy.

Methods: Eligible oncologists/pulmonologists in the United States, Europe (France, Germany, and United Kingdom), and Japan completed electronic case report forms for patients with mNSCLC (no evidence of alterations). Eligible patients had disease progression on/after an anti-PD-(L)1 and platinum-doublet chemotherapy (received concurrently or sequentially), initiated a subsequent line of therapy (LOT) between 2017 and 2021, and had an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at this subsequent LOT initiation (index date).

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Atezolizumab (anti-PD-L1), combined with carboplatin and etoposide (CE), is now a standard of care for extensive-stage small-cell lung cancer (ES-SCLC). A clearer understanding of therapeutically relevant SCLC subsets could identify rational combination strategies and improve outcomes. We conduct transcriptomic analyses and non-negative matrix factorization on 271 pre-treatment patient tumor samples from IMpower133 and identify four subsets with general concordance to previously reported SCLC subtypes (SCLC-A, -N, -P, and -I).

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Neuregulin 1 () fusions are oncogenic drivers that have been detected in non-small-cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC) and other solid tumors. fusions are rare, occurring in less than 1% of solid tumors. Patients with fusion positive (NRG1+) cancer have limited therapeutic options.

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Purpose: Non-small-cell lung cancer (NSCLC) with has inferior outcomes to immune checkpoint inhibitors (ICIs). Using multiomics, we evaluated whether a subtype of NSCLC with a uniquely inflamed tumor immune microenvironment (TIME) harboring comutations could have favorable outcomes to ICIs.

Patients And Methods: NSCLC tumors (N = 16,896) were analyzed by next-generation sequencing (DNA-Seq/592 genes).

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Survival beyond 2 years is rare in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemotherapy alone. We describe a patient with ES-SCLC who was treated with carboplatin, etoposide and the programmed death-ligand 1 inhibitor atezolizumab in the IMpower133 study (ClinicalTrials.gov registration: NCT02763579) and who achieved exceptionally long-term survival.

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Objectives: Neuregulin-1 (NRG1) fusions may drive oncogenesis via constitutive activation of ErbB signaling. Hence, NRG1 fusion-driven tumors may be susceptible to ErbB-targeted therapy. Afatinib (irreversible pan-ErbB inhibitor) has demonstrated activity in individual patients with NRG1 fusion-positive solid tumors.

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Background: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied.

Methods: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities.

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Purpose: The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by the addition of tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) and overall survival (OS) analyses.

Methods: Patients received tiragolumab 600 mg/placebo, plus atezolizumab 1,200 mg and CE (four cycles), then maintenance tiragolumab/placebo plus atezolizumab.

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