EGFR E746

In summary, there are limited prospective data to guide therapy in patients with rare EGFR mutations. Prospective studies are required to evaluate the response to endothelial growth factor receptor-tyrosine kinase inhibitors in patients with rare EGFR mutations in order to ensure patient safety and response to treatment in this patient population.

We also studied preclinical Ba/F3 models expressing EGFR -K745_E746insIPVAIK (Ba/F3-IPVAIK) and EGFR -delE746_A750 (Ba/F3-Del19) to investigate the sensitivity to 1st-generation (gen) (gefitinib and erlotinib), 2nd-gen (afatinib, dacomitinib, and poziotinib), 3rd-gen (osimertinib), and EGFR exon 20 insertion active TKIs (mobocertinib, sunvozertinib, and zipalertinib). The preclinical therapeutic window of Ba/F3-IPVAIK and Ba/F3-Del19 for all the 2nd generation TKIs were similarly favorable, whereas Ba/F3-IPVAIK had much unfavorable therapeutic windows to other EGFR-TKIs compared to Ba/F3-Del19. Conclusions : Our clinical and preclinical findings indicate 2nd-gen EGFR-TKIs are more effective than 1st and 3rd-gen EGFR-TKIs in patients with EGFR exon 19 insertions.

Five patients were treated with matched targeted therapy, with three having durable benefit: (i) erlotinib for EGFR-altered tumor, followed by osimertinib/capmatinib when MET amplification emerged (first-line therapy); (ii) pralsetinib for RET fusion (fifth line); and (iii) dabrafenib/trametinib for BRAF N486_P490del (third line). Sustained therapeutic benefit can be achieved in a real-world setting in a subset of patients with advanced/metastatic KRAS-WT PDAC treated with chemotherapy-free matched targeted agents. Prospective studies are warranted.

We also present a case demonstrating a favorable response to the dual therapy of olaparib and osimertinib in NSCLC harboring EGFR, RAD50, and ARID1A mutations that progressed on osimertinib. There were 2298 patients in the NSCLC cohort (MSKCC database). HRD aberrations are uncommon in EGFR mutated lung cancer patients. Further investigation on the role of PARP inhibitor in EGFR mutated lung cancer is warranted.

Our case indicated that the feasibility of neoadjuvant icotinib in EGFR-mutant lung adenosquamous carcinoma.

Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

Oral administration of D-mannose strongly inhibited tumor growth in mice, showing similar effects with osimertinib. Taken together, these data suggest that D-mannose may represent a new strategy for clinical treatment of NSCLC.

Our study revealed potential differences in TKI efficacy, resistance mechanism, and prognosis of various EGFR ex19del subtypes in NSCLC, underscoring the need for precise selection of first-line therapy.

These results suggest that specific mutations in EGFR exon 20 play a crucial role in SIP development, partially though hyper-activation of the PI3K/AKT and MAPK signaling pathways. This study presents the first in vitro model for SIP development, which could facilitate further investigations into SIP pathogenesis and preclinical studies for new therapeutic agents.

The research used three patient-derived organoids (PDOs) to explore the efficacy of combo [chemotherapy (chemo) plus TKI or bevacizumab] treatment...EGFR 19del or L858R-mutant proteins could be constantly expressed, and EGFR pathway still existed in EGFR-mutant transformed SCLC/NEC with a common clonal origin from the baseline LUAD. Taking together, these molecular characteristics potentially favored clinical efficacy in transformed SCLC/NEC treated with the combo regimen.

Updated results will be presented (data cutoff, December 2021). Table: 151P Efficacy according to mutation status

Accordingly, the patient continued Osimertinib combined with Carboplatin/Pemetrexed and with additional palliative irradiation due to a new symptomatic spinal cord compression at L3. Acquired EML4-ALK fusion represents an extremely rare (1%) acquired mechanism of Osimertinib-resistance, which enables further effective and feasible therapy by combining EGFR- and ALK-TKI. Rebiopsies, when possible, are of noteworthy value even in heavily pretreated and fragile patients.