EGFR L858R + EGFR exon 21 deletion

This case underscores the transient efficacy of targeted therapy in SMARCA4-deficient NSCLC with concurrent EGFR mutations. It highlights the need for continuous therapeutic adjustments and emphasizes the importance of further research into effective strategies for treating this complex and challenging subset of NSCLC, as current modalities have limitations in sustained efficacy.

This study will offer better perspectives on the efficacy and safety of osimertinib plus bevacizumab combination therapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation, providing valuable guidance for clinical practice.

SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.

The differential effect of treatment by smoking was not explained by TP53 mutation or other molecular alterations examined. Molecular mechanisms of acquired resistance were detected but no novel molecular alterations were identified in the combination arm.

The median PFS in the dose reduction group was significantly prolonged compared with that in the standard dose group (26.0 months vs. 12.0 months, p = 0.03). Multivariable analysis of 84 patients, excluding a patient with unknown brain metastasis, revealed that EGFR exon 21 L858R mutation, malignant pleural effusion or pleural metastasis, liver metastasis, and dose reduction within 6 months were independent factors affecting PFS. Early dose reduction of osimertinib is an effective therapeutic strategy for prolonging PFS in patients with EGFR-mutated NSCLC.

Median overall survival (95% CI) was 21.30 (15.86-26.75) months. Lower afatinib doses (<40 mg OD) could be equally effective as standard dose in patients with EGFR-mutant advanced NSCLC and may be more suited to Asian patients, minimizing side effects that may occur at higher dosages of afatinib leading to dose interruptions and affecting treatment outcomes.

The anti-PD-1 inhibitor-based combinational therapy elicited exciting anti-tumor efficacy and prolonged patient survival with manageable adverse effects in NSCLC patients harboring oncogenic alterations. The PD-L1 status and LIPI could be used as a biomarker predicting response to anti-PD-1 inhibitor-based combinational treatment in these patients.

In addition, the probability of disease progression over time was higher for L858R compared with that for exon 19 deletion mutation, in patients with central nervous system metastasis (log-rank test, p = 0.027). The mutation subtype had an impact not only on the clinical outcome of the first-line OSI treatment but also on progression patterns after OSI treatment in patients with NSCLC harboring EGFR mutations.

The rate of OPD of patients receiving first line osimertinib was 77 %. Patients with OPD had a significantly better OS compared to patients with SPD (51.6 vs. 26.4 months). Patients with OPD receiving LAT had the longest median OS (60.0 months).

High RBM10 expression and PD-L1 positivity are poor prognostic factors for OS in patients with pN1-N2 EGFR-Mt lung adenocarcinoma after curative surgery. In patients with recurrent pN1-N2 EGFR-Mt lung adenocarcinoma, PD-L1 and RBM10 expression may influence response to EGFR-TKIs.

No abstract available

PD-L1 TPS ≥20% in patients with EGFR-mutated NSCLC may be associated with early resistance to osimertinib.

P1, N=37, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jan 2023 --> Jul 2023

Patient received erlotinib 150 mg daily as frontline treatment in December 2018. We present the case of a patient with advanced stage NSCLC, with EGFR mutation, Secondary T790M positive and MET amplification, received osimertinib and capmatinib as third-line treatment. The efficacy was different from previous report (1), using both combination in EGFR mutation, T790M negative, MET-amplified patient, emphasizing the marginal effect in this subgroup.

The prevalence rate of coexisting MET exon 14 mutations and EGFR sensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2%,and the management of these subtype is not identified.This patient has received significant clinical benefits from antivascular drugs combined with chemotherapy sequential third generation EGFR-TKI Aumolertinib therapy, especially the sustained remission of intracranial lesions, which provides a reference for our clinical treatment of such patients. Case presentation. In November 2021,a 47-year-old male patient developed head discomfort with left lower limb weakness for 1 week.Brain MRI showed multiple intracranial lesions, which were considered to be brain metastases.In order to identify the primary lesion,CT showed a soft tissue mass in upper lobe of the right lung and mediastinal lymphadenopathy.To determine the pathological type,In December 2021,he underwent a lung biopsy, whose path report showed lung adenocarcinoma.The patient was diagnosed with right lung adenocarcinoma(T1N2M1,IV),accompanied by mediastinal lymph nodes and brain metastases.In an effort to control the symptoms of central nervous system(CNS) more quickly,bevacizumab combined with PC regimen was administered before genetic testing results are available.After 2 cycles of treatment,the lung and intracranial masses achieved a partial response(PR).Subsequently, polymerase chain reaction (PCR) detection revealed the simultaneous presence of EGFR exon 21 L858R and MET exon14 skipping mutations.Due to the lack of effective treatment method(Currently, there is insufficient evidence to support the therapy strategies of combining EGFR-TKI and MET inhibitor in such patients), aumolertinib, the third-generation EGFR-TKI approved in China 2020, was monotherapy given 110 mg per day orally.The reexamination found that the lung and intracranial masses of the patient were further narrowing and maintained PR, and the metastatic lesions in the left frontal lobe were also shrank,while the enhancement lesion disappeared.Up to now, this patient has achieved a PFS of more than 14 months.Of note,there were no significant drug-related adverse events during the treatment period,and he is still under a close follow-up. In this case, we reported a NSCLC patient with EGFR-sensitive combining MET Exon 14 Skipping mutations, who obtained a remarkable curative effect after aumolertinib, especially the CNS lesions have been continuously relieved. In this case, we reported a NSCLC patient with EGFR-sensitive combining MET Exon 14 Skipping mutations, who obtained a remarkable curative effect after aumolertinib, especially the CNS lesions have been continuously relieved. This was the first report applied aumolertinib to patients with EGFR and MET co-mutations, which providing us with a reference for treatment of such patients. Currently, phase Ib clinical trial of aumolertinib combined with c-MET inhibitor(HS-10241) are being conducted in patients with advanced NSCLC(NCT05430386), and will provide a promising treatment plan for the survival of such patients in the future.