scholarly journals Significance of EGFRGene Mutation in Fresh Cytological Specimens of Lung Adenocarcinoma

1970 ◽  
Vol 2 (2) ◽  
Author(s):  
Xiao Guo ◽  
Rui Wang ◽  
Juan Wu ◽  
Xiaokun Ji ◽  
Heng Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Needle Aspiration ◽  
Chemotherapy Group ◽  
Tissue Specimens ◽  
Medical University

Objective:This paper aims to study the mutation of epidermal growth factor receptor (EGFR) gene in fresh cytological specimens from patients with lung adenocarcinoma, and to determine the prognosis of positive patients by tyrosine kinase inhibitor (TKI). Methods: A total of 313 specimens from needle aspiration and pleural effusion were collected in the Cancer Detection Center of the Fourth Hospital of Hebei Medical University. After HE and immunocytochemistry stainings, the specimens were diagnosed as lung adenocarcinoma by two cytology pathologists. Themutation of 18-21 exon was detectied using ARMS to observe mutations situation. Then, the objective response rate (ORR) and the progression-free survival (PFS) between the targeted group and the chemotherapy group of patients were comparedith. Results: Among 313 cases, 293 cases of lung adenocarcinoma were diagnosed, and DNA specimens were extracted from 288 cases. The success rate was about 98.3%. 130 mutations were found and the rate was 45.1%. EGFR mutation of adenocarcinoma patients mainly occurred to females, nonsmokers, but had nothing to do with age. The ORR was statistically different between the targeted group with chemotherapy (P<0.01), and PFS curve of targeted group was on chemotherapy group. The efficacy and the survival time of targeted group and targeted and chemotherapy group were superior to that of chemotherapy group. The results of the EGFR mutation and the prognosis of the tested positive patients in the fresh cytology samples were consistent with that from previous literatures. Conclusion: The results of the testwere accurate, and fresh cytological specimens can be used as a replacement for tumor tissue specimens.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

scholarly journals Early serum tumor marker levels after fourteen days of tyrosine kinase inhibitor targeted therapy predicts outcomes in patients with advanced lung adenocarcinoma

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0240736
Author(s):  
Hung-Jen Chen ◽  
Chih-Yen Tu ◽  
Kuo-Yang Huang ◽  
Chun-Ru Chien ◽  
Te-Chun Hsia
Keyword(s):  
Targeted Therapy ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Mutation Status ◽  
Anaplastic Lymphoma

Objective Image evaluation strategy for lung cancer patients has difficulty obtaining the appropriate quantity of diffuse lung nodules and bone metastases. The study was to demonstrate whether early variations in the levels of serum 4-tumor markers (4-TMs)(carcinoembryonic antigen [CEA], cancer antigen [CA]125, CA19-9, and CA15-3) after TKI targeted therapy were associated with treatment response in patients with lung adenocarcinoma. Methods Patients with stage IIIB-IV lung adenocarcinoma taking epidermal growth factor receptor (EGFR) TKIs or anaplastic lymphoma kinase (ALK) inhibitors were enrolled prospectively from June 2012 to February 2015. According to the variations of the percentage of change in 4-TM levels (4-TMpc), we divided patients into ascending (increases in 4-TMpc over the 7th- 14th day) and descending (decreases in 4-TMpc over the 7th- 14th day) groups. Results 184 patients were enrolled, and 89% had at least one of the pre-treatment evaluable TMs and were further analyzed. An excellent response to the TKI targeted therapy was accurately predicted in the descending group, as determined using receiver operating characteristic curve analysis (an area under the curve, 0.83). Multivariate Cox hazards model analyses demonstrated that the type of 4-TMpc and mutation status were the strongest predictors of progression-free survival (PFS)(descending versus ascending, hazard ratios [HR] 0.30, 95% confidence interval [CI], 0.19–0.47; sensitive mutation versus wide type, HR 0.30, 95% CI, 0.19–0.48). Conclusions Type of 4-TMpc 14 days after TKI targeted therapy is associated with an image response and PFS, without regarding mutation status, in patients with advanced lung adenocarcinoma.

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]

Anlotinib in chemotherapy-refractory metastatic esophageal squamous cell carcinoma (ESCC): A randomized, double-blind, multicenter phase II trial.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 95-95 ◽  
Author(s):  
Jing Huang ◽  
Juxiang Xiao ◽  
Wentao Fang ◽  
Ping Lu ◽  
Qingxia Fan ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Double Blind ◽  
Duration Of Response ◽  
Grade 3 ◽  
Vegfr Inhibitor ◽  
Loss Of Appetite

95 Background: The treatment option for ESCC patients (pts) progressing after chemotherapy is still uncertain. Anlotinib is a multi-target tyrosine kinase inhibitor involved in tumor angiogenesis and growth, such as vascular endothelia growth factor receptor (VEGFR) 2/3, etc. Methods: Eligible pts were advanced ESCC who had progressed after platinum or taxane containing chemotherapy. Between January 6, 2016 and May 22, 2018, a total of 165 pts from 13 centers in China were randomly assigned (in a 2:1 ratio) to anlotinib arm (n=110), and placebo arm (n=55). Pts were given anlotinib (12 mg/day) or placebo orally from day 1 to day 14 in a 21-day cycle until disease progression or had unacceptable toxic effects. The primary end point was progression-free survival (PFS). Results: Median PFS was 3.0 months with anlotinib and 1.4 months with placebo (HR 0.5, 95% CI, 0.3-0.7; P<0.0001). Complete response occured in 2 pts with anlotinib and 0 pt with placebo. The objective response rates were 7% in the anlotinib group and 4% in the placebo group (P=0.498), and the disease control rates (DCR) were 64% and 18%, respectively (P<0.0001). In anlotinib arm, median duration of response was 5.8 months (range, 3.1-19.7+). Grade 3/4 treatment-related adverse events (TRAE) were reported in 36.7% and 11.0% of the two group pts, and grade 5 TRAE were 2.8% and 0%, respectively. The most common grade 3/4 TRAE (>5%) in anlotinib arm were hypertension (15.6%) and loss of appetite (5.5%). Median overall survival were similar between the groups (6.1 months vs 7.2 months; HR 1.2, 95%CI 0.8-1.8, P=0.4261). The ratio of pts received post study treatments was 41.2% (40/97) in anlotinib arm and 72.7% (40/55) in placebo arm (P=0.0002), including chemotherapy (23.7% vs 54.6%), PD-1 inhibitors (4.1% vs 11.0%), and Apatinib, a VEGFR inhibitor, (10.3% vs 20.0%), etc. Conclusions: In pretreated advanced ESCC pts, anlotinib significantly improved PFS and DCR compared with placebo, with a manageable safety profile. Clinical trial information: NCT02649361.

Randomized phase II study of olaparib with or without cediranib in men with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 111-111 ◽  
Author(s):  
Joseph W. Kim ◽  
Rana R. McKay ◽  
Mary-Ellen Taplin ◽  
Nancy B. Davis ◽  
Paul Monk ◽  
...  
Keyword(s):  
Dna Repair ◽  
Radiographic Progression ◽  
Kinase Inhibitor ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Tumor Biopsy

111 Background: Cediranib, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, suppresses expression of BRCA1, BRCA2, and RAD51 and increases sensitivity of tumors to poly (ADP-ribose) polymerase (PARP) inhibitors in vitro. Olaparib, a PARP inhibitor, demonstrates clinical efficacy in men with DNA repair deficient, mCRPC. We therefore performed a randomized phase 2 trial comparing olaparib with or without cediranib in men with mCRPC. Methods: Men with a minimum of one prior line of systemic therapy for mCRPC were randomized 1:1 to receive cediranib 30mg po daily plus olaparib 200mg po BID (Arm A) or olaparib 300mg BID alone (Arm B). At radiographic progression, patients (pts) in Arm B could crossover to Arm A. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints were objective response rate (ORR) and PSA50 decline rate (PSA50). Tumor biopsy specimens were obtained for biomarker analyses pre- and on-treatment. Results: Baseline characteristics of the 90 pts enrolled are summarized below. The median rPFS was 11.1 versus 4.0 months in Arm A and Arm B, respectively (Hazard Ratio 0.54, 95% CI 0.317, 0.928, p=0.026). Trends toward a higher ORR (19% and 12%), Disease Control Rate (Stable Disease + Partial Response) (77% and 64%,) and PSA50 (29% and 17%) were observed in Arm A compared to Arm B, respectively. Thirteen pts in Arm B crossed over to Arm A. One pt had a PR after crossover. Grade 3/4 adverse events (G3/4 AEs), irrespective of attribution, occurred in 77% and 58% of Arm A and Arm B pts, respectively. G3/4 AEs occurring in >10% of pts were hypertension (32%), fatigue (23%) and diarrhea (11%) in Arm A, and anemia (16%) and lymphopenia (11%) in Arm B. Conclusions: The cediranib/olaparib combination significantly improves rPFS in unselected, mCRPC pts. AEs were manageable. Analyses of mutation status in homologous recombination DNA repair genes are pending and will be key in interpreting the data. Clinical trial information: NCT02893917. [Table: see text]

scholarly journals Lung adenocarcinoma in a patient with Li–Fraumeni syndrome bearing a novel germ-line mutation, TP53R333Vfs*12

2020 ◽  
Vol 50 (10) ◽  
pp. 1214-1217 ◽  
Author(s):  
Shodai Takahashi ◽  
Kazuhiro Shimazu ◽  
Koya Kodama ◽  
Koji Fukuda ◽  
Taichi Yoshida ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Germ Line ◽  
Growth Factor Receptor ◽  
Triple Mutant ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni ◽  
Egfr Tki

Abstract Germline mutations of TP53 are responsible for Li–Fraumeni syndrome in its 60–80%. We found a novel germline mutation, TP53: c.997del:p.R333Vfs*12 (NM_000546.6, GRCh, 17:7670713..7670713). The proband is a 40-year-old female, who was suffered from osteosarcoma in her right forearm at her age of 11. She was also suffered from lung adenocarcinoma in her right upper lobe and bone metastasis in her right scapula at her age of 37. She was treated with gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) because of EGFR mutation (L747-S752 del). Her bone metastasis became resistant after 1-year treatment. Bone metastasis had an additional EGFR mutation (T790M). The secondary treatment with osimertinib, an another EGFR-TKI, can successfully control the tumors for over 2 years. This TP53 mutation (R333Vfs*12) was first found in lung adenocarcinomas. The therapeutic effect of osimertinib for this triple mutant lung adenocarcinoma is better than the previous report.

scholarly journals Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial

2020 ◽  
Vol 38 (34) ◽  
pp. 4095-4106
Author(s):  
Chunyan Lan ◽  
Jingxian Shen ◽  
Yin Wang ◽  
Jundong Li ◽  
Zhimin Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Duration Of Response ◽  
Grade 3

PURPOSE Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

scholarly journals Apatinib Plus Temozolomide: An Effective Salvage Treatment for Recurrent Glioblastoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Jingjing Ge ◽  
Cheng Li ◽  
Fengjun Xue ◽  
Shaopei Qi ◽  
Zhimeng Gao ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Symptomatic Treatment ◽  
Recurrent Glioblastoma ◽  
Salvage Regimen ◽  
Common Grade ◽  
Grade 3 ◽  
Endothelial Growth Factor

BackgroundTreatment for recurrent glioblastoma is poor, and there is a need for better therapies. Here we retrospectively assessed the efficacy and toxicity of temozolomide plus apatinib, an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 in recurrent glioblastoma.Materials and MethodsA retrospective analysis of patients with recurrent glioblastoma who underwent apatinib plus temozolomide treatment was performed. Apatinib was given at 500 mg once daily. Temozolomide was administered at 200 mg/m2/d on days 1–5 or 50 mg/m2/d continuous daily according to whether they had experienced temozolomide maintenance treatment before. The main clinical data collected included tumor characteristics, status of MGMT promoter, and IDH mutation, number of relapse, response, survival, adverse reactions, and salvage therapies.ResultsFrom April 2016 to August 2019, thirty-one patients were identified. The objective response rate was 26.3%, and the disease control rate was 84.2%. The progression-free survival (PFS) at 6 months and overall survival (OS) at 12 months were 44.6 and 30.2%. The median PFS and OS were 4.9 and 8.2 months, respectively. Two patients achieved long PFS of 30.9 and 38.7+ months. The median survival time after progression of the patients with or without salvage bevacizumab was 5.1 versus 1.2 months. The most common grade 3 or 4 toxicities were hypertension (5.8%), decreased appetite (5.8%), and thrombocytopenia (4.3%), most of which were resolved after symptomatic treatment or dose reduction.ConclusionApatinib plus temozolomide is an effective salvage regimen with manageable toxicities for recurrent glioblastoma and could not reduce the sensitivity to bevacizumab.

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