Publications by authors named "Hossein Borghaei"

What Is This Summary About?: This is a summary of a phase 2 clinical study called DeLLphi-301. The study looked at how effective and safe a medicine called tarlatamab was in participants with small cell lung cancer (SCLC). Participants previously received at least two other treatments for their SCLC.

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  • * A pooled analysis of clinical trials showed that patients receiving this combination treatment had better overall survival (17.4 months) compared to those receiving chemotherapy alone (11.3 months) at a median follow-up of 73.7 months.
  • * The combination treatment also resulted in higher progression-free survival and objective response rates without new safety concerns, making it a promising first-line option for hard-to-treat NSCLC cases.
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  • - This study examines treatment patterns and real-world overall survival (rwOS) in patients with extensive-stage small cell lung cancer (ES-SCLC) after the introduction of anti-PD-L1 therapies in 2019 and 2020.
  • - Researchers analyzed a nationwide database, focusing on patients who received systemic therapy from 2013 to 2021, finding that etoposide plus platinum chemotherapy was the most common first-line treatment.
  • - Despite the use of anti-PD-L1 therapies, the median overall survival rates for patients were relatively low: 8.3 months for those treated with 1L anti-PD-L1 compared to 8.0 months for those who were not, indicating ongoing challenges
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  • Tarlatamab, an immunotherapy targeting delta-like ligand 3, shows promising anticancer effects in small cell lung cancer (SCLC) based on the DeLLphi-300 and DeLLphi-301 trials, with manageable safety profiles.
  • In the extended follow-up of DeLLphi-300, the overall response rate was 25%, with a median duration of response of 11.2 months and a median overall survival of 17.5 months across 152 patients.
  • Among those receiving a specific dose regimen (10 mg every two weeks), 35.3% experienced a response, and notable intracranial tumor shrinkage was found in patients with existing brain lesions, highlighting tarlatam
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Introduction: Squamous cell cancer (SqCC) is a lung cancer subtype with few targeted therapy options. Molecular characterization, that is, by next-generation sequencing (NGS), is needed to identify potential targets. Lung Cancer Master Protocol Southwest Oncology Group S1400 enrolled patients with previously treated stage IV or recurrent SqCC to assess NGS biomarkers for therapeutic sub-studies.

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Lung cancer, the leading cause of cancer-related deaths globally, remains a pressing health issue despite significant medical advances. The New York Lung Cancer Foundation brought together experts from academia, the pharmaceutical and biotech industries as well as organizational leaders and patient advocates, to thoroughly examine the current state of lung cancer diagnosis, treatment, and research. The goal was to identify areas where our understanding is incomplete and to develop collaborative public health and scientific strategies to generate better patient outcomes, as highlighted in our "Calls to Action.

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  • Tumors can spread to other parts of the body even after treatment, which can be very dangerous and lead to death.
  • Some cancer cells can go inactive and hide in places within the body before they come back to life and form new tumors later on.
  • Scientists are studying how to stop these hidden cancer cells from waking up and causing more problems, especially in the lungs, by understanding how they interact with the body's environment and other cells.
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  • The study investigates treatment patterns and outcomes for real-world SCLC patients in the US who underwent three or more lines of therapy, highlighting the complexities of their care.
  • It analyzed a group of 326 patients, revealing median overall survival of 5.3 months and a progression-free survival of 2.5 months after receiving three lines of treatment.
  • The findings emphasize the poor efficacy of current therapies for advanced SCLC and highlight the urgent need for new treatment options.
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Unlabelled: The most common oncogenic driver mutations for non-small cell lung cancer (NSCLC) activate EGFR or KRAS. Clinical trials exploring treatments for EGFR- or KRAS-mutated (EGFRmut or KRASmut) cancers have focused on small-molecule inhibitors targeting the driver mutations. Typically, these inhibitors perform more effectively based on combination with either chemotherapies, or other targeted therapies.

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For cancer clinical trials that require central confirmation of tumor genomic profiling, exhaustion of tissue from standard-of-care testing may prevent enrollment. For Lung-MAP, a master protocol that requires results from a defined centralized clinical trial assay to assign patients to a therapeutic substudy, we developed a process to repurpose existing commercial vendor raw genomic data for eligibility: genomic data reanalysis (GDR). Molecular results for substudy assignment were successfully generated for 369 of the first 374 patients (98.

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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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Introduction: In patients with advanced NSCLC (aNSCLC), the impact of KRAS mutations (m) and comutations with STK11 and KEAP1 on outcomes across different PD-L1 levels remains incompletely understood. We aimed to investigate the frequency of KRAS mutations and comutations across PD-L1 levels, and the association between these mutations and survival, stratified by PD-L1 expression.

Methods: We conducted a nationwide cohort study of patients diagnosed with aNSCLC between 2016 and 2021 treated with frontline (chemo)immunotherapy, who underwent molecular genotyping including KRAS, STK11, and KEAP1.

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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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Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies.

Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance).

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Background: Mixed response (MR), a scenario featuring discordant tumor changes, has been reported primarily with targeted therapies or immunotherapy. We determined the incidence and prognostic significance of MR in advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy.

Patients And Methods: We analyzed patient-level data from ECOG-ACRIN E5508 (carboplatin-paclitaxel + bevacizumab induction followed by randomization to maintenance therapy regimens).

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  • A modified version of the PGDx elio Plasma Resolve assay was validated as a laboratory-developed test for clinical use at Fox Chase Cancer Center, capable of detecting specific genetic variants in cancer patients using plasma DNA.
  • The assay identified 66 single nucleotide variants (SNVs) and 23 small insertions/deletions (indels) with high sensitivity (95.5% for SNVs and 70.4% for indels), and specificity of 92.3% at defined allele frequencies.
  • An inter-laboratory study showed a strong agreement (91.7% positive percent agreement) with another test, demonstrating its reliability for diagnostic purposes.
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  • Tarlatamab is a bispecific T-cell engager immunotherapy that showed promising results in a phase 1 trial for patients with previously treated small-cell lung cancer.
  • In a phase 2 trial involving 220 patients, tarlatamab was administered intravenously every 2 weeks at doses of 10 mg or 100 mg, with an objective response rate of 40% and 32% respectively.
  • The study found that common side effects included cytokine-release syndrome, decreased appetite, and fever, with overall survival rates at 9 months being 68% for the 10-mg group and 66% for the 100-mg group.
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Background: The incidence of lung cancer in the US has been decreasing but a bigger decline has been observed in men despite similar declines in tobacco use between men and women. Multiple theories have been proposed, including exposure to exogenous estrogens. Our study seeks to understand the relationship between hormone receptors (HR), gender, and the genomic landscape of non-small lung cancer (NSCLC).

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•Mutations in the gene are observed in about 15% of NSCLC adenocarcinomas in the United States and are not associated with smoking. There are numerous mutations, with the most common being exon 19 deletions and the point mutation L858R in exon 21.•Osimertinib, an oral TKI, is used as the initial therapy for metastatic NSCLC harboring exon 19 deletion and exon 21 L858R mutation.

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This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ.

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Introduction: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab.

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Over the past decade, the advent of molecular techniques and deeper understanding of the tumor microenvironment (TME) have enabled the development of a multitude of immunotherapy targets and approaches. Despite the revolutionary advancement in immunotherapy, treatment resistance remains a challenge leading to decreased response rate in a significant proportion of patients. As such, there has recently been an evolving focus to enhance efficacy, durability, and toxicity profiles of immunotherapy.

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  • The Targeted Agent and Profiling Utilization Registry Study is testing the effectiveness of targeted treatments for advanced lung cancer patients with specific genomic alterations.
  • The study involved 28 patients, primarily with non-small-cell lung cancer, who received a combination therapy of pertuzumab and trastuzumab, aiming for disease control and measuring various outcomes, including overall survival.
  • Results indicated a 37% disease control rate, with some patients showing a partial response, though there were also notable serious side effects from the treatment.
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