The impact of eligibility criteria on KRASG12C inhibitor trials in patients with NSCLC.

Background: 20% of cancer patients are estimated to be ineligible for phase III trials due to restrictive eligibility criteria. In response, several groups, including the FDA, have advocated for more inclusive study designs. We examined KRAS G12C inhibitor trials to determine if inclusivity has shifted in the development of molecularly-targeted therapies.

Phase 3 Trials of Neoadjuvant, Perioperative, and Adjuvant Chemoimmunotherapy for Resectable, Early-Stage NSCLC: Comprehensive Review and Detailed Analysis.

Phase 3 trials of neoadjuvant, perioperative, and adjuvant immune checkpoint inhibitors combined with chemotherapy (ICI-CT) in resectable early-stage NSCLC (eNSCLC) have reported that all three approaches confer an event-free or disease-free survival benefit over CT alone, with acceptable safety profiles. All three strategies are approved standards of care for eNSCLC. This review provides a detailed analysis of these phase 3 ICI-CT trials and addresses the considerations regarding the selection of each approach, including protocol schema and baseline patient and tumor differences, preoperative staging, surgical outcomes, efficacy end points, safety, treatment disposition, and the programmed death-ligand 1 (PD-L1) efficacy biomarker.

Central Nervous System Metastases from Primary Lung Carcinoma: Significance of RNA Fusion Testing and Early Versus Late Metastases.

While the genomic landscape of primary lung carcinomas is well characterized, there is a relative scarcity of fusion data on corresponding central nervous system (CNS) metastases. This study aimed to elucidate the molecular profiles of CNS metastases to (1) assess the significance of a combined DNA-reflex RNA fusion testing approach and (2) compare the mutational landscape between patients who present initially [early (≤2 months)] with CNS metastases and those who develop CNS metastases thereafter [late (>2 months)]. : We performed a retrospective search of CNS metastases of adenocarcinoma of probable lung origin interrogated by targeted DNA-reflex RNA next-generation sequencing (NGS).

Amivantamab in Participants With Advanced NSCLC and MET Exon 14 Skipping Mutations: Final Results From the CHRYSALIS Study.

Introduction: Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity. We assessed the safety and efficacy of amivantamab in participants with advanced NSCLC harboring primary MET exon 14 skipping mutations (METex14).

Methods: CHRYSALIS enrolled participants with METex14 NSCLC who progressed after or declined standard-of-care therapy.

Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases.

Brain metastases frequently develop in patients with non-small cell lung cancer (NSCLC) and are a common cause of cancer-related deaths, yet our understanding of the underlying human biology is limited. Here we performed multimodal single-nucleus RNA and T cell receptor, single-cell spatial and whole-genome sequencing of brain metastases and primary tumors of patients with treatment-naive NSCLC. Chromosomal instability (CIN) is a distinguishing genomic feature of brain metastases compared with primary tumors, which we validated through integrated analysis of molecular profiling and clinical data in 4,869 independent patients, and a new cohort of 12,275 patients with NSCLC.

Deconstructing the Monolith: An Educational Module for Understanding Disparities Within Asian American, Native Hawaiian, and Pacific Islander Populations.

Introduction: Asian American, Native Hawaiian, and Pacific Islander (AANHPI) people represent one of the largest and most rapidly growing groups in the United States and are often aggregated as a homogeneous, rather than diverse, population in medical research and education. Currently, few educational interventions focus on the disaggregation of AANHPI patient populations and the improvement of knowledge about health disparities that affect AANHPI patients.

Methods: We developed, implemented, and facilitated a workshop for medical students to address AANHPI health disparities, adaptable for in-person and online formats.

Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A.

Introduction: Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 cohort A evaluated amivantamab plus lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy. Primary end point was investigator-assessed objective response rate (ORR).

Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings.

Introduction: Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy.

Methods: This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery.

Weight loss in patients on osimertinib for metastatic EGFR-mutant non-small cell lung cancer.

Background: Cachexia is characterized by weight loss and decline in muscle mass and function and is a poor prognostic factor among patients with cancer. Patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) derive remarkable survival benefits with osimertinib, a third-generation EGFR tyrosine kinase inhibitor. It is not known whether patients treated with osimertinib experience any weight loss or whether weight loss impacts patient outcomes.

Unusual presentation of rearranged metastatic non-small cell lung cancer.

The spectrum of clinical and radiographic presentations of lung adenocarcinoma is increasingly broad, including in the metastatic setting. Here, we report on a patient who initially presented with a mild chronic cough that remained stable over a decade, with serial CT scans showing gradual worsening of multifocal areas of consolidation and ground-glass opacities of the bilateral lungs. The patient was ultimately diagnosed with rearranged lung adenocarcinoma and achieved a dramatic response with entrectinib.

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From and Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC).

Purpose: Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor () mutations and anaplastic lymphoma kinase () rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.

Materials And Methods: Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States.

A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies.

Unlabelled: Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions.

Neoadjuvant immunotherapy in resectable non-small-cell lung cancer.

The advent of immune checkpoint inhibition has pushed the treatment paradigm for resectable non-small-cell lung cancer (NSCLC) toward neoadjuvant therapy. A growing number of promising trials have examined the utility of neoadjuvant immunotherapy, both alone and in combination with other modalities such as radiation therapy (RT) and chemotherapy. The phase II LCMC3 and NEOSTAR trials demonstrated a role for neoadjuvant immunotherapy in inducing meaningful pathologic responses, and another phase II trial established the feasibility of combining neoadjuvant durvalumab with RT.

Management of infusion-related reactions (IRRs) in patients receiving amivantamab in the CHRYSALIS study.

Background: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related reaction(s) (IRR[s]) are reported commonly with amivantamab. We review IRR and subsequent management in amivantamab-treated patients.

Unusual Adverse Events in a Patient With BRAF-Mutated Non-Small Cell Lung Cancer Treated With BRAF/MEK Inhibition.

BRAF/MEK inhibition remains standard of care for treatment of BRAF-mutated non-small cell lung cancer (NSCLC). Although common adverse events (AEs) have been reported through clinical trials and ongoing clinical practice, only a handful of reports have detailed unusual adverse events associated with these medications. This report presents a patient with BRAF-mutated NSCLC treated with dabrafenib and trametinib who experienced 2 unusual AEs-Sweet syndrome and MEK-associated retinopathy-that responded to steroid treatment.

CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFR-Mutated NSCLC: A Brief Report.

Introduction: CD73 is overexpressed in EGFR-mutated NSCLC and may promote immune evasion, suggesting potential for combining CD73 blockers with EGFR tyrosine kinase inhibitors (TKIs). This phase 1b-2 study (NCT03381274) evaluated the anti-CD73 antibody oleclumab plus the third-generation EGFR TKI osimertinib in advanced EGFR-mutated NSCLC.

Methods: Patients had tissue T790M-negative NSCLC with TKI-sensitive EGFR mutations after progression on a first- or second-generation EGFR TKI and were osimertinib naive.

Self-Renewing CD8+ T-cell Abundance in Blood Associates with Response to Immunotherapy.

Treatment with immune checkpoint blockade (ICB) often fails to elicit durable antitumor immunity. Recent studies suggest that ICB does not restore potency to terminally dysfunctional T cells, but instead drives proliferation and differentiation of self-renewing progenitor T cells into fresh, effector-like T cells. Antitumor immunity catalyzed by ICB is characterized by mobilization of antitumor T cells in systemic circulation and tumor.

Assessing Pathologic Response in Resected Lung Cancers: Current Standards, Proposal for a Novel Pathologic Response Calculator Tool, and Challenges in Practice.

The efficacy of neoadjuvant treatment for NSCLC can be pathologically assessed in resected tissue. Major pathologic response (MPR) and pathologic complete response (pCR), defined as less than or equal to 10% and 0% viable tumor cells, respectively, are increasingly being used in NSCLC clinical trials to establish them as surrogate end points for efficacy to shorten time to outcome. Nevertheless, sampling and MPR calculation methods vary between studies.