159P: Early radiological response (ERR) as predictor of overall survival in non small cell lung cancer (NSCLC) patients with EGFR mutations

e20636 Background: Activation of MET oncogene as the result of amplification or activation MET exon 14 mutations represents an emerging molecular target for non-small cell lung cancer (NSCLC) treatment. MET exon 14 mutations account for 1.0% in Chinese NSCLC patients. However, few data have been reported on the coexisting of MET exon 14 mutations and EGFR mutations in NSCLC. Moreover, the clinicopathological characteristics and targeted therapy of these MET/ EGFR-coexisting patients remain elusive. Methods: Next-generation sequencing was performed on the DNA of 969 patients and Sanger sequencing was conducted on cDNA of 621 patients for MET exon 14 mutations in NSCLCs. EGFR mutations were determined by direct DNA sequencing. Results: Fifteen patients harbored positive MET exon 14 mutations. Frequency of concomitant EGFR and MET exon 14 mutations was 0.2%(3/1590). 3 patients with concomitant MET exon 14 mutation and EGFR activating mutation were all female, never smokers and adenocarcinoma. Their stagings were stageⅠB (n = 1) and stage Ⅳ(n = 2). The stage ⅠB patient harboring concomitant MET exon 14 skipping and EGFR L858R mutation did not relapse 2 years after operation. The other two stage Ⅳ patients received first-line gefitinib. Case one harbored concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR exon 19 deletion, and showed resistance to gefitinib with progression free survival(PFS) of 2 weeks and overall survival(OS) of 1 month. Case two had concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR L858R mutation. Meanwhile, she also had both METamplification and c-Met overexpression at the baseline. She showed partial response (PR) to gefitinib with 3.8 months PFS. Then she was enrolled in a clinical trial (NCT02374645) to receive volitinib plus gefitinib on December 20, 2016. Initial response was good PR on January 24, 2017. Only grade 1 rash was observed. Conclusions: Coexisting MET exon 14 /EGFR mutation is an uncommon molecular event in NSCLC patients. Such coexisted patients might show relative resistance to EGFR inhibitor. However, combination of MET and EGFR inhibitors will be potentially a good strategy to overcome such a relative resistance for MET exon 14 /EGFR co-mutant patients.

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The Presence of EGFR Mutations Predicts the Response in Chinese Non-Small Cell Lung Cancer Patients Treated with Erlotinib

The International Journal of Biological Markers ◽

10.5301/jbm.5000059 ◽

2014 ◽

Vol 29 (2) ◽

pp. 112-119 ◽

Cited By ~ 2

Author(s):

Rui-chao Li ◽

Li-jun Zheng ◽

Ming-hao Fang ◽

Shi-ying Yu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Stage Iiib ◽

Egfr Mutations ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients ◽

Line Chemotherapy

Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. The upregulation of the epidermal growth factor receptor (EGFR) due to mutations has been observed in a number of cancers, and tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, which specifically target EGFR signaling, have been used to treat NSCLC patients. The presence of EGFR mutations was previously shown to confer sensitivity to TKIs. In this study, we evaluated the correlation between EGFR mutations and response to erlotinib in Chinese NSCLC patients. We recruited 36 patients with stage IIIB/IV NSCLC who had failed first-line chemotherapy, and treated them with erlotinib. We used immunohistochemistry to determine EGFR expression, and we screened for mutations using PCR analysis. We used Cox regression analysis and Kaplan-Meier curves for survival analysis. We found that 8 patients had exon 19 mutations, while 3 patients had exon 21 mutations. An Eastern Cooperative Oncology Group (ECOG) grade of 2 was a significant negative predictor of overall survival (OS). Patients with EGFR mutations showed a significantly better OS compared to those without EGFR mutations. Additionally, multivariate analysis showed that erlotinib-treated stage IV patients had a significantly longer progression-free survival (PFS) compared to stage IIIB patients. Patients with EGFR mutations also had a significantly better PFS compared to those without EGFR mutations. The overall remission rate (22.2%) and disease control rate (75%) were significantly higher compared to the rates after second-line chemotherapy (<10%). In conclusion, the presence of EGFR mutations could be a marker to predict the therapeutic efficacy of erlotinib and the prognosis in Chinese NSCLC patients.

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RET Inhibitors in Non-Small-Cell Lung Cancer

Cancers ◽

10.3390/cancers13174415 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4415

Author(s):

Priscilla Cascetta ◽

Vincenzo Sforza ◽

Anna Manzo ◽

Guido Carillio ◽

Giuliano Palumbo ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Phase Iii ◽

Egfr Mutations ◽

Small Cell Lung ◽

Good Tolerability ◽

Phase Ii Studies ◽

Nsclc Patients

RET rearrangements are observed in 1–2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.

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Dissociated responses at initial computed tomography evaluation is a good prognostic factor in non-small cell lung cancer patients treated with anti-program cell death-1/ligand 1 inhibitors

10.21203/rs.2.16868/v1 ◽

2019 ◽

Author(s):

Takehiro Tozuka ◽

Satoru Kitazono ◽

Hiroaki Sakamoto ◽

Hiroshi Yoshida ◽

Yoshiaki Amino ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Cell Death ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Proportional Hazards ◽

Small Cell ◽

Small Cell Lung ◽

Nsclc Patients ◽

Program Cell Death

Abstract Background Dissociated responses (DR) are phenomena in which some tumors shrink, whereas others progress during treatment of patients with cancer. The purpose of the present study was to evaluate the frequency and prognosis of DR in non-small cell lung cancer (NSCLC) patients treated with anti-program cell death-1/ligand 1 (anti-PD-1/L1) inhibitors. Methods This retrospective study included NSCLC patients who received anti-PD-1/L1 inhibitor as second- or later-line treatment. We excluded patients without radiological evaluation, including brain imaging within 28 days prior to the treatment, and those without measurable lesions. We evaluated all measurable lesions in each organ. We defined DR as a disease with some shrinking lesions as well as growing or emerging new lesions in patients who showed progressive disease (PD), according to the RECIST 1.1 at the initial CT evaluation. Cases not classified as DR were defined as ‘true PD’. Overall survival was compared between patients with DR and those with true PD using Cox proportional hazards models. Results The present study included 62 NSCLC patients aged 27–82 years (median: 65 years). DR and true PD were observed in 11 and 51 patients, respectively. Nivolumab, pembrolizumab, and atezolizumab were administered to 45, 7, and 10 patients, respectively. Median overall survival was significantly longer in patients with DR versus true PD (14.0 vs. 6.6 months; hazard ratio for death: 0.40; 95% confidence interval: 0.17–0.94). Conclusions The frequency of DR in NSCLC patients who showed PD to anti-PD-1/L1 was 17.7%. Patients with DR exhibited a relatively favorable prognosis.

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