P1.01-85 Treatment for Advanced NSCLC with EGFR Mutations and De Novo MET Amplification/Overexpression

2019 ◽  
Vol 14 (10) ◽  
pp. S393
Author(s):  
H. Wang ◽  
W. Li ◽  
Q. Deng ◽  
J. Kang ◽  
H. Chen ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
De Novo ◽  
Egfr Mutations ◽  
Met Amplification

The combination of EGFR-TKIs and anlotinib as a first-line therapy for EGFR-mutant advanced non-small cell lung cancer: A multicenter, single-arm, phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9030-9030
Author(s):  
Zhiyong He ◽  
Jinghui Lin ◽  
Yueming He ◽  
Jing Zhang ◽  
Dongyong Yang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Advanced Nsclc ◽  
De Novo ◽  
Egfr Mutations ◽  
Treatment Naïve ◽  
Pre Treatment ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

9030 Background: Currently,EGFR-TKIs are widely accepted as the standard treatment for EGFR- mutant advanced non-small-cell lung cancer (NSCLC); however, acquired resistance is inevitable. Combination therapy is considered as a strategy to overcome the resistance to EGFR-TKIs. Anlotinib, a novel multi-targeting, small-molecule TKI, has shown active to suppress tumor angiogenesis and growth. However, there is still a lack of evidence supporting the use of EGFR-TKIs in combination with anlotinib for the treatment of NSCLC until now. A multi-center, single-arm, phase II clinical trial was therefore designed to examine the efficacy and safety of EGFR-TKIs combined with anlotinib for treatment-naïve, advanced NSCLC patients, and unravel the possible mechanisms. Methods: This study was conducted in 14 research centers in Fujian, China. The main eligibility criteria were stage IV or relapsed nonsquamous NSCLC with EGFR mutations (exon 19 deletion,, and L858R), ECOG score 0-2,and age 20 to 75 years and no previous systemic treatment. Patients with asymptomatic brain metastases were admitted.Eligible patients were given gefitinib (250 mg QD) or icotinib (125 mg TID) in combination with anlotinib (10 mg per day, on days 1‒14; 21 days per cycle) until disease progression. The primary endpoint is progression-free survival (PFS) and safety, and the secondary endpoint is overall survival (OS), objective response rate (ORR) and disease control rate (DCR).Peripheral blood was sampled pre-treatment, once every two months during treatment and after disease progression, and T790M mutation was detected in plasma ctDNA using a droplet digital PCR (ddPCR) assay. Results: Of 60 patients enrolled (August 2, 2018 to May 28, 2020). As of February 1, 2021, 37 patients (61.7%) experienced PFS events and 10 (16.7%) died. The ORR was 78.3%, and the DCR was100%.Median PFS was 13.0 months (95%CI,10.7-15.3).The 5 most common treatment-related adverse events included rash (63.3%), fatigue (55.0%), hypertension (48.3%), diarrhea (33.3%) and hand-foot syndrome (30.0%), and grade 3 adverse events included hypertension (5.0%), rash (1.67%), hypertriglyceridemia (1.67%), vomiting (1.67%) and elevated ALT (1.67%); no grade 4 adverse events or drug-related deaths were observed. Peripheral blood samples were collected from 36 patients pre-treatment, and 30.6% were identified with low-frequency de novo T790M mutations, with the mutation-allele frequency (MAF) ranging from 0.01% to 0.28%. Conclusions: The combination of the first-generation EGFR-TKIs and anlotinib shows impressive ORR and DCR, and acceptable toxicity in treatment-naïve advanced NSCLC patients with activating EGFR mutations, and we observed a high proportion of patients harboring de novo EGFR T790M mutations in this study. Clinical trial information: NCT03720873.

scholarly journals De-novo EGFR mutation and MET amplification in NSCLC with crizotinib response; a case against one-gene/one-drug paradigm

2015 ◽  
Vol 26 ◽  
pp. vii126
Author(s):  
Simon Y-R. Ang ◽  
Miah-Hiang Tay ◽  
Eunice B-J. Ng ◽  
Peter C-S. Ang ◽  
Benjamin Y-S. Chuah
Keyword(s):  
Egfr Mutation ◽  
De Novo ◽  
Met Amplification

Tepotinib in Patients with Advanced NSCLC with MET Amplification (METamp)

2022 ◽  
Vol 112 (2) ◽  
pp. e6-e7
Author(s):  
X. Le ◽  
R. O'Hara ◽  
L. Paz-Ares ◽  
J.P. Van Meerbeeck ◽  
S. Viteri Ramirez ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Met Amplification

scholarly journals Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1412-1417 ◽  
Author(s):  
MJ Ratain ◽  
LS Kaminer ◽  
JD Bitran ◽  
RA Larson ◽  
MM Le Beau ◽  
...  
Keyword(s):  
Combination Chemotherapy ◽  
Advanced Nsclc ◽  
De Novo ◽  
Cumulative Risk ◽  
Late Complications ◽  
Small Cell ◽  
First Year ◽  
Acute Nonlymphocytic Leukemia ◽  
Acute Monoblastic Leukemia ◽  
High Doses

Combination chemotherapy is frequently used in the therapy of advanced non-small-cell lung cancer (NSCLC), but late complications are rarely recognized because of the short survival of most patients. Of 119 patients with advanced NSCLC treated with cisplatin and other drugs, four patients developed acute nonlymphocytic leukemia (ANLL). All four patients received etoposide and cisplatin with or without vindesine. Leukemia was diagnosed at 13, 19, 28, and 35 months after start of treatment. Three patients had morphologic and/or cytogenetic features of acute leukemia with significant monoblastic involvement; the fourth patient had trilineage dysplasia and cytogenetic abnormalities more commonly associated with therapy-related leukemia. Detailed analysis of the subgroup who survived longer than 1 year (24 patients) suggests that high cumulative doses of etoposide are leukemogenic; the median etoposide dose was 6,795 mg/m2 (first year only) in the four leukemic patients compared with 3,025 mg/m2 in the 20 nonleukemic patients (P less than .01). The rate of ANLL was 0.30 per person-year after the first year (95% confidence limits 0.11 to 0.90), with a cumulative risk of 15% +/- 11% at 2 years, and 44% +/- 24% at 2.5 years. We conclude that high doses of etoposide are potentially leukemogenic, and can induce a syndrome with features of acute monoblastic leukemia de novo that is distinct from other secondary leukemias.

Genomic landscape differences in patients with advanced non-small cell lung cancer by sex and age.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9108-9108
Author(s):  
ErinMarie Kimbrough ◽  
Hiba I. Dada ◽  
Leylah Drusbosky ◽  
Yujie Zhao ◽  
Rami Manochakian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Age Groups ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Genomic Alterations ◽  
Genomic Landscape

9108 Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related death in the U.S. The median age at diagnosis is 70 years, and NSCLC is uncommon among younger individuals ( < 50 years).Overall, outcomes in NSCLC have improved significantly with targeted therapy. A prior study demonstrated patients < 50 are more likely to have targetable alterations including EGFR, ALK, ERBB2, and ROS1. Another study reported an increased prevalence of EGFR mutations in females and KRAS mutations in males with NSCLC. The comprehensive genomic landscape of NSCLC patients in different age groups and genders remains largely unknown. In our study, we aim to investigate the genomic alterations in patients with advanced NSCLC according to age and sex. Efforts that are focused on identifying targetable alterations in NSCLC will likely help personalize treatment and improve outcomes. Methods: We performed a retrospective review of de-identified data from the Guardant Health database from March 2018 through October 2020. We reviewed 34,237 profiles from patients with NSCLC who underwent molecular profiling using the plasma-based circulating-tumor DNA (ctDNA) Next-Generation Sequencing (NGS) assay Guardant360. Single nucleotide variants (SNV), fusions, indels and copy number variations (CNV) of up to 83 genes were analyzed. We assessed for genomic differences among patients with advanced NSCLC by both sex and age (≥70 and < 70). We conducted two-tailed tests of equality of proportions comparing males to females and ≥70 to < 70. Results: Of the 34,237 profiles reviewed, somatic alterations were seen in 81.7% (n = 27,972) of the patients. The median age was 70 (range 16-102) and 55% were female. Our study demonstrated that the most common genomic alterations in both age groups and genders were TP53, EGFR, KRAS, ATM, and MET. Patients ≥70 were more likely to have ATM (21% versus 14%, p < 0.0001) and MET (12% versus 10 %, p < 0.0001) mutations than those < 70. Patients < 70 were more likely to have EGFR (30% versus 27%, p < 0.0001), STK11 (14% versus 11%, p = 0.0056), and KRAS (26% versus 24%, p < 0.0001) alterations. EGFR was seen more frequently in females (33% versus 26%, p < 0.0001). ATM (11% versus 6%, p < 0.0001) and MET (8% versus 5%, p = 0.0050) were seen more frequently in males. Conclusions: Significant differences in the distribution of targetable genomic alterations were identified among different age groups and genders in patients with advanced NSCLC. These findings highlight the importance of taking personalized approaches to diagnostic testing and treatment of advanced NSCLC.

Clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20588-e20588
Author(s):  
Linping Gu ◽  
Bei Zhang ◽  
Ding Zhang ◽  
Hong Jian
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
De Novo ◽  
Egfr Mutations ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Genetic Characteristics ◽  
Egfr Mutant ◽  
Lung Adenocarcinomas ◽  
Egfr T790m

e20588 Background: Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of the resistance mechanism of EGFR tyrosine kinase inhibitors. However, the clinical course of transformed SCLC and the difference of genomic profiling between de novo SCLC patients and transformed SCLC patients are still poorly characterized. Methods: Patients from our hospital diagnosed with SCLC were enrolled retrospectively in this study, including de novo SCLC patients and SCLC patients transformed from EGFR-mutant lung adenocarcinomas. Genomic profiling was performed on formalin-fixed paraffin-embedded tumor samples by next generation sequencing (NGS). In statistical analysis, fisher ‘exact test was used. All tests were bilateral, with P<0.05 indicating significant statistical difference. Results: In total, 16 patients with SCLC transformed from EGFR-mutant lung adenocarcinomas and 230 de novo SCLC patients were included in our study. Transformed SCLC patients were more in younger (p=0.007), female (p<0.001) and non-smokers (p<0.001) than de novo SCLC patients. In transformed SCLC patients, 12 patients (75%) occurred SCLC transformation within 2 years after the lung adenocarcinomas diagnosis. Median transformation time was 20 months. During the treatment of adenocarcinomas, the overall response rate (ORR) was 75% and the median progression-free survival was 12 months. After the initiation of SCLC therapy, the ORR of 1st line chemotherapy was 40%. For the genomic profiling, EGFR mutations, including exon 19 deletion (56%), L858R (38%), and others (6%), were detected. 11 patients with acquired resistance were received EGFR T790M test, 82% of patients had acquired EGFR T790M mutation. 11 patients after transformation to SCLC had NGS test, 100% maintained their founder EGFR mutation, and other recurrent mutations included TP53, RB1 and EGFR amplification. Compared with the genetic alterations in de novo SCLC patients, TP53 mutations were significantly decreased (p=0.006) while EGFR mutations were significantly elevated (p<0.001) in transformed SCLC patients. However, no significant difference on RB1, ALK and ROS1 mutations were observed. Interestingly, a 60-year-old woman in our transformed SCLC cohort harbored EGFR 19 del mutant at allele frequency of 50.39%，she received osimertinib plus epirubicin/cyclophosphamide as 1st line treatment and reached partial response, with survival of 4 years to date. Conclusions: We demonstrated the clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC and found one patient still benefited from EGFR-TKI. Our study suggested that SCLC patients with EGFR mutation who transformed from lung adenocarcinoma may be potential benefit population using EGFR inhibitors.

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