Disease control with a second epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after failure of a first TKI in Asian patients with non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18104-18104
Author(s):  
A. Wong ◽  
S. W. Lim ◽  
T. M. Chin ◽  
R. Soong ◽  
R. A. Soo
Keyword(s):  
Disease Control ◽  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Patient Characteristics ◽  
University Hospital ◽  
Bronchioloalveolar Carcinoma ◽  
Histologic Subtype ◽  
Molecular Features ◽  
Nsclc Patients ◽  
Egfr Tki

18104 Background: Asian NSCLC patients are known to have higher response rates to the EGFR TKI gefitinib (G) and erlotinib (E). Anecdotal reports suggest some activity for a second EGFR TKI after failure of the first. Methods: A retrospective review of the electronic pharmacy records, clinical and radiographic records of patients with advanced NSCLC at the National University Hospital who received both G and E in the previous 2 years was conducted. Objectives were to assess the disease control (response/stable disease) of the second TKI after failure of the first and characterize the clinical, pathological and molecular features of patients benefiting from a 2nd TKI. Results: 14 patients with advanced NSCLC who received a 2nd EGFR TKI after progression on the 1st TKI were identified. Patient characteristics: Chinese 12, female 10, and non-smokers 13. Histologic subtype: adenocarcinoma 7, bronchioloalveolar carcinoma (BAC) 3, squamous-cell carcinoma 1, NSCLC unspecified 3. 12 patients received cytotoxic chemotherapy with a median of 2 lines, (range 1–5). G and E was used as 1st/2nd/3rd/=4th line treatment in 8/2/2/2 and 0/4/2/8 patients respectively. G was used before E in 13 cases and disease control was seen in 8/14 (57%) patients. With a 2nd TKI after disease progression, disease control was seen 4/14 (28%) patients. Patient characteristics were: adenocarcinoma 3, BAC 1, all were never smokers and all received and responded to prior G. Median duration of control in these 4 patients for G was 8 (range 7–12) months, and subsequently to E was 2.5 (range 2–8) months. Disease control was associated with symptomatic improvement. Conclusion: This study documents disease control in 28% of Asian NSCLC patients treated with a second EGFR TKI after failure of a first. The molecular basis for these observations is currently being investigated. No significant financial relationships to disclose.

Rare and complex mutations of epidermal growth factor receptor (EGFR) and efficacy of tyrosine kinase inhibitor (TKI) in patients with non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7566-7566
Author(s):  
Bhumsuk Keam ◽  
Dong-Wan Kim ◽  
Jin Hyun Park ◽  
Jeong-Ok Lee ◽  
Tae Min Kim ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Case Series ◽  
University Hospital ◽  
Similar Treatment ◽  
Group A ◽  
Group B ◽  
Exon 20 ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Exon 19

7566 Background: Other than in-frame deletional mutation (MT) in exon 19 and Leu858Arg point MT in EGFR gene, there are many rare and complex MT. The purpose of this study was to investigate was to clarify the clinical significance of rare and complex MT, and the efficacy of EGFR TKI in these patients. Methods: Rare MTs were defined any MT other than deletional MT in exon 19, Leu858Arg in exon 21, and Thr790Met in exon 20. Complex MT was defined two different EGFR MTs co-occurring within the single tumor sample. We have analyzed consecutive database of NSCLC patients who were treated with either gefitinib or erlotinib at Seoul National University Hospital between Jan. 2002 and Dec. 2011. For analysis of EGFR MT, coding sequences from exon 18 to 21 were amplified by nested PCR and subjected to direct sequencing methods. Results: Among the 1,159 TKI treated patients, 301 patients had EGFR MT (177 patients (58.8%) with del-19, 104 patients (34.6%) with Leu858Arg, and 20 patients (6.6%) with rare MT). Twenty-three (7.6%) patients have complex MT, and 55 (18.3%) patients have Gln787Gln polymorphism particularly associated with Leu858Arg MT. Identified rare MT were follows; exon 18: Leu692Phe, Glu707Lys, Glu709Gly, Lys714Asn, Gly7Ala, Thr725Thr, exon 19: Ala755Asp Lys737Thr, exon 20: Val786Met, exon21: Ala871Gly, Gly873Gln, Leu833Val, Val834Leu, Arg836Cys, Pro848Leu, Ala859Thr, Leu861Gln. When categorizing 3 groups (group A: classic MT alone, group B: complex MT with classic + rare MT, group C: rare MT alone or complex MT with rare MTs), response rate (RR) to TKI was different between each groups (RR= 78.7% in group A vs. 69.2% in group B vs. 38.5% in group C, respectively, P < 0.001). Progression-free survival (PFS) was also poorer in rare MT (median PFS: 12.1 mo vs. 7.6 mo vs. 2.1 mo, respectively, P= 0.020,). Gln787Gln polymorphism of exon 21 was not associated with RR or PFS (P= 0.101, P= 146, respectively) Conclusions: In this large case series, NSCLC patients who harboring rare MT other than del-19 and Leu858Arg, does not seems response to EGFR TKI. However, complex MT with the classical MT showed similar treatment efficacy toward EGFR TKI with that of classical MT alone.

Autoantibodies indicating diagnostic or prognostic value in NSCLC patients were identified by protein microarrays.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20638-e20638
Author(s):  
Rongrong Luo ◽  
Caixia Liang ◽  
Jiarui Yao ◽  
Di Wu ◽  
Zhishang Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Data ◽  
Prognostic Value ◽  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Protein Microarrays ◽  
Positive Rate ◽  
Nsclc Patients ◽  
Egfr Tki

e20638 Background: Autoantibodies(AAbs) have been recently recognized as auxiliary diagnostic biomarkers in lung cancer. Applying high-throughput protein microarrays to address AAbs profile of non-small cell lung cancer(NSCLC) is rarely studied. Herein, we aimed to discover AAbs possessing diagnostic or prognostic value in NSCLC patients. Methods: We collected pretreatment plasma samples and survival data of 258 NSCLC patients and 343 controls. The advanced NSCLC patients were divided into subgroups according to different epidermal growth factor receptor(EGFR) gene status, therapies and therapeutic response. We utilized human proteomic(HuprotTM) microarrays to screen differential AAbs and customized microarrays to validate. Statistical methods were Chi-square test and ROC analysis. Results: We found 8 AAbs(p < 0.05 or AUC > 0.6) with underlying diagnostic or prognostic value of NSCLC patients after screening and validation. The positive rate of 4 AAbs including anti-TP53, XAGE1A1,2 and KCNAB1 in NSCLC group were higher than that in controls. Among them, anti-KCNAB1 increased in early-stage group compared with controls, indicating early diagnostic value. The other three AAbs level raised as disease progressed to advanced-stage. For advanced NSCLC patients, the differential AAbs of EGFR+ patients receiving either first generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy or chemotherapy were identified with higher positive rate in poor response subgroups compared with good response subgroups(Table1). However, for EGFR- patients with chemotherapy, the differential AAbs in different response subgroups were not found. Conclusions: We found AAbs with underlying diagnostic or prognostic value for advanced NSCLC patients receiving EGFR-TKI or chemotherapy, which should be further investigated to confirm their clinical value. [Table: see text]

scholarly journals Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

Activity of tivozanib (AV-951) in patients (Pts) with different histologic subtypes of renal cell carcinoma (RCC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 327-327 ◽  
Author(s):  
P. Bhargava ◽  
B. Esteves ◽  
M. Al-Adhami ◽  
D. Nosov ◽  
O. N. Lipatov ◽  
...  
Keyword(s):  
Disease Control ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Histologic Subtype ◽  
Papillary Rcc ◽  
Vegfr Inhibitor ◽  
Histologic Subtypes

327 Background: This phase 2 randomized discontinuation trial evaluated tivozanib, a potent and selective vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 kinase inhibitor. Median progression-free survival (PFS) in all pts was 11.8 mo, and the objective response rate (ORR) was 27%. Methods: Pts received 1.5 mg/d tivozanib (3 wk on, 1 wk off = 1 cycle). A retrospective analysis evaluated efficacy and safety by histologic subtype. Response was evaluated by independent radiology review using standard RECIST criteria. Results: 272 pts were enrolled: 70% were male; median age was 56 y (range, 26–79). 226 (83%) pts had clear cell (CC) RCC; 46 had non–clear cell (NCC) RCC, including 11 with papillary RCC. Of pts with CC RCC, 176 (78%) had undergone nephrectomy; of pts with NCC RCC, 23 (50%) had undergone nephrectomy. Median treatment duration was 8.5 mo (range, 0.03– 23.8) as of the data cutoff. Median PFS was 12.5 mo (range, 9.9–17.7) for pts with CC RCC, not yet reached for pts with papillary RCC, and 5.4 mo (range, 3.7–12.0) for pts with other NCC subtypes. ORR and disease control rate (DCR; ORR + stable disease), respectively, were 29% and 85% for pts with CC RCC, 18% and 100% for pts with papillary RCC, and 17% and 74% for pts with other NCC subtypes. For pts with CC RCC, median PFS, ORR, and DCR, respectively, were 14.8 mo, 32%, and 88% for those who had undergone nephrectomy and 8.9 mo, 18%, and 76% for those who had not. Among pts with NCC RCC, median PFS was 6.6 mo for pts who had undergone nephrectomy and 7.2 mo for pts without nephrectomy; ORR was 17% for both NCC subgroups, with a DCR of 78% for pts who had undergone nephrectomy and 83% for pts who had not. Common drug- related adverse events (AEs) for pts with CC and NCC RCC, respectively, included hypertension (49% and 48%), dysphonia (22% and 22%), asthenia (12% and 13%), and diarrhea (13% and 9%). The most common grade ≥3 drug-related AE was hypertension (CC, 8%; NCC, 4%). Conclusions: Disease control was observed for pts with all RCC histologic subtypes. The rate of AEs was similar among patients with CC and NCC RCC and consistent with that of a selective VEGFR inhibitor with minimal off-target toxicities. Tivozanib is currently being tested in a phase 3 trial in pts with CC RCC. [Table: see text]

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