EGFR fusion

This is the first study that describes the clinical, pathological, and molecular characteristics of MPE patients due to NSCLC in a Caucasian population. Although overall we did not find significant differences in the molecular profile between patients with MPE and without effusion, EGFR mutation was associated with a tendency towards pleural progression.

Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.

Conclusions Comprehensive ctDNA NGS can identify driver EGFR mts and other informative co-alts for patients with LUAD. Frequency and types of such co-alts are mostly similar in AME and other regions.

Importantly, co-occurrence of rare fusions and EGFR classical activating mutations in patients pre-treated with anti-EGFR therapy suggests a potential resistance mechanism and consideration of upfront, dual mutation, targeted treatment to improve outcomes. Further clinical studies are needed to validate the best treatment options for these patients with rare fusions.

We identify a previously unappreciated cDC mechanism mediating Treg tumor infiltration after RT. Our findings suggest blocking the cDC1-CCL22-Treg axis augments RT efficacy. αEGFR-IFNα added to RT provided robust antitumor responses better than systemic free interferon administration, and may overcome clinical limitations to interferon therapy. Our findings highlight the complex behavior of cDC after RT and provide novel therapeutic strategies for overcoming RT-driven immunosuppression to improve RT efficacy.

All patients harboring a targetable alteration were >50 years of age and most of them had >15 pack-years, questioning restrictive molecular testing strategies. Based on our real-world data, we propose a reflex testing workflow using DNA- and RNA-based NGS that includes all newly diagnosed NSCLC cases, irrespective of histology, but also irrespective of age or smoking status.

In summary, EGFRvIII is rare, occurring primarily in glioblastoma and rarely in breast sarcomatoid neoplasm, with no instances identified in other tumor types in our series. This select group of patients may benefit from chemotherapy and/or targeted anti-EGFR therapy.

On June 20, 2020, the patient's treatment regimen was as following: (1)Anti-tumor: aumolertinib 110mg qd; (2)Intracranial pressure reduction: mannitol 250mg q12h, glycerin fructose 125ml q12h; (3)Improve cardiac function: furosemide 20mg qd, spironolactone 20mg bid; (4)Epilepsy control: Levetiracetam + phenobarbital sodium, intermittent administration of midazolam; (5)Nutritional support therapy: Rego 1000ml tube feeding qd (1500Kcal); (6) Puncture and drainage of pleural effusion, oxygen therapy, airway management.Three days later, the patient regained consciousness, no seizures occurred again. In this case, we reported a right lung adenocarcinoma cT3N3M1 patient with brain metastasis, malignant pleural effusion, and a positive EGFR 19del mutation who obtained a remarkable curative effect and good tolerance,after treatment with aumolertinib. This was the first report successfully applied aumolertinib to an EGFR sensitive lung patient with brain metastases with epilepsy as the initial symptom and in poor physical condition, and suggested the fast and good therapeutic potential of aumolertinib in this population.

The only notable adverse event was grade 3 elevated transaminase, that was effectively managed by dose reduction. These data may support the use of selpercatinib in patients with RET/EGFR co-mutated NSCLC.

EGFR-TKI treatment is effective for MPE of EGFR-mutant LUAD patients, especially for those harboring exon 19 deletion.

The results supported the lack of a general association with high PD-L1 and high TMB calls for biomarker informed treatment options for nsqNSCLC patients. We reported a subpopulation of nsqNSCLC patients that can be described by certain genetic alteration, of which some were associated with ICI-related biomarkers for which patients might benefit from a future precision oncology approach utilizing combined targeted and ICI treatment.

Osimertinib-resistant YU-1097 harboring EGFR resistance mutation (E19del/T790M/C797S) revealed sensitivity to BLU-945 (IC50, 108nM), a novel fourth-generation EGFR-TKI. A similar inhibition of cell viability was observed with repotrectinib (IC50, 21nM), a next-generation ROS1-TKI and lorlatinib (IC50, 9nM) in YU-1078 harboring CD74-ROS1, whereas more robust tumor regression was seen with repotrectinib in YU1078-derived xenograft model. Amivantamab, a EGFR-MET bispecific antibody, showed a robust activity in YU-1163 and YUO-036 in vitro and in vivo. PDC/PDO models can be utilized for evaluating activity of novel agents and will accelerate novel drug development in NSCLC.