Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung tumor marked by significant molecular heterogeneity. In a study of 590 patients across two independent cohorts, we observe comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identifies distinct non-small cell lung cancer-like (NSCLC-like, KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles.

Early Weight Gain as a Risk Factor for Increased Maximum Weight Gain Among Patients With NSCLC on Lorlatinib and Other ALK Tyrosine Kinase Inhibitors.

Introduction: Therapy-associated weight gain affects the quality of life and health of patients with ALK-positive NSCLC treated with tyrosine kinase inhibitors (TKIs). The severity and timing of real-world weight gain on ALK TKIs and associated risk factors are poorly understood, impairing timely interventions.

Methods: A retrospective chart review of patients with ALK-positive NSCLC receiving TKIs at our institution from January 1, 2020 to December 31, 2023 was conducted.

Increased accrual of diverse patient populations in oncology phase I clinical trials at the University of Colorado Cancer Center.

Background: Disparities in cancer outcomes persist between racial, ethnic, and socioeconomic groups. One potential cause is lack of appropriate representation in dose-finding clinical trials. We investigated the extent of disparities in phase I clinical trials and recent changes in the setting of institutional efforts to mitigate disparities, legislative interventions, FDA guidance for sponsors and the COVID-19 pandemic.

Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer: Update From the COAST Randomized Clinical Trial.

Importance: The PACIFIC trial established durvalumab as the standard-of-care therapy for unresectable, stage III non-small cell lung cancer (NSCLC) without progression following concurrent chemoradiotherapy (cCRT). Novel immunotherapy combinations involving the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab have the potential to build on the durvalumab standard of care.

Objective: To report updated results from the phase 2 COAST trial of consolidation durvalumab alone or combined with oleclumab or monalizumab in patients with unresectable, stage III NSCLC and no progression following cCRT.

Activity of Brigatinib in Patients With Crizotinib-Resistant ALK-positive Non-Small-Cell Lung Cancer According to ALK Fusion and Mutation Status.

Background: Brigatinib, a selective ALK inhibitor, demonstrated preclinical activity against a range of crizotinib-resistant ALK alterations in NSCLC. We examined associations between brigatinib efficacy and tumor- and plasma-detected driver mutations in crizotinib-resistant ALK fusion-positive NSCLC.

Patients And Methods: Tumor tissue and plasma circulating tumor DNA (ctDNA) from patients with crizotinib-exposed ALK-positive NSCLC receiving brigatinib in phase 1/2 and phase 2 ALTA trials were analyzed by next-generation sequencing.