*February 2023* Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. In the Phase III FLAURA study (NCT02296125), first-line osimertinib improved outcomes vs comparator EGFR-TKIs in EGFRm advanced non-small cell lung cancer. This analysis identifies acquired resistance mechanisms to…

*March 2023* The antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (Enhertu) met the prespecified target for objective response rate (ORR) and demonstrated durable responses in heavily pretreated patients with HER2-expressing advanced solid tumors in the phase 2 DESTINY-PanTumor02 trial (NCT04482309).1 The trial included previously treated patients with locally advanced, unresectable, or metastatic…

*April 2023* There is still a lot to be learned regarding resistance mechanisms in EGFR-mutant NSCLC, especially when osimertinib is used in the first-line setting and especially in the category of pathway indifference resistance cancers. In this issue of the Journal of Thoracic Oncology, Choudhury et al.10 set out to characterize mechanisms of…

*February 2023* RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today provided updates on two Phase 3 trials, KEYNOTE-641 and KEYNOTE-789. Merck also announced that the Phase 3 KEYNOTE-789 trial evaluating KEYTRUDA in combination with pemetrexed plus platinum-based chemotherapy did not meet its…

*January 2023* Introduction Epidermal growth factor receptor (EGFR) mutations drive a subset of non-small cell lung cancer (NSCLC). Patients harboring the common EGFR mutations, deletion of exon 19 (Ex19del) and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. However, the effect of osimertinib on NSCLC with atypical EGFR…

*November 2022* The uncommon EGFR mutations remain a perennial challenge to treat. They constitute a heterogenous group of molecular alterations within exons 18 to 21, which include substitution mutations of G719X, L861Q, and S768I, and exon 20 insertions, with prevalence of approximately 10% to 20% of EGFR mutation-positive NSCLC. EGFR mutations…

*January 2023* In an interview with OncLive®, Spira highlighted the top advancements across NSCLC in 2022, emphasized the need for increased genetic testing to inform treatment decisions, and previewed other agents under development. Spira is the co-director of the Virginia Cancer Specialists Research Institute and the Phase I Trial Program, the…

*January 2023* Note: This is a deep dive into ADCs that are currently being used inside and outside clinical trials for lung cancers expressing HER2 or HER3 mutations as well as other mutations that occur after first- and second-line therapies. Antibody-drug conjugates (ADCs) are, arguably, the fastest-growing class of oncology drugs in…

*January 2023* The ASCO Living Guideline for advanced non-small cell lung cancer (NSCLC) with driver alterations has gotten its first update, with data from recent studies -- DESTINY-Lung01 and CodeBreaK100 -- incorporated into the guidance. In the update, published in the Journal of Clinical Oncology, Dwight H. Owen, MD, MS, of the Ohio State University in Columbus,…

*November 2022* Antibody-drug conjugates targeting receptor tyrosine-protein kinase erbB-2 (ERBB2, HER2) have emerged as promising targeted options for HER2-mutant NSCLC. Among antibody-drug conjugates targeting HER2, trastuzumab deruxtecan was found to have the most impressive efficacy and is a potential new standard of care. Drug-related interstitial lung disease remains a serious unpredictable…