Phase 1 Study of the Efficacy and Safety of Ramucirumab in Combination with Osimertinib in Advanced T790M-Positive EGFR-Mutant Non-Small Cell Lung Cancer:
Purpose: We report the final analysis of JVDL (NCT02789345), which examined the combination of the EGFR TKI osimertinib plus the VEGFR2-directed antibody ramucirumab in patients with T790M-positive EGFR-mutant NSCLC. Experimental Design: This open-label, single-arm phase 1 study enrolled patients with EGFR T790M-positive NSCLC, who had progressed following EGFR TKI but were third-generation EGFR TKI-naïve. A dose-limiting toxicity (DLT) period with as-needed dose de-escalation was followed by an expansion cohort. Patients received daily oral osimertinib and intravenous ramucirumab every 2 weeks until progression or discontinuation. Results: Twenty-five patients were enrolled. No DLTs were observed. Median follow-up time was 25.0 months. Common Grade 3 or higher treatment-related adverse events (TRAEs) were hypertension (8%) and platelet count decreased (16%); Grade 5 TRAE (subdural hemorrhage) occurred in one patient. Patients with (N=10) and without CNS metastasis (N=15) had similar safety outcomes. Five patients remain on treatment. Objective response rate (ORR) was 76%. Median duration of response was 13.4 months (90% CI: 9.6-21.2). Median progression-free survival (PFS) was 11.0 months (90% CI: 5.5-19.3). Efficacy was observed in patients with and without CNS metastasis (ORR 60% and 87%; median PFS 10.9 and 14.7 months, respectively). Exploratory biomarker analyses in circulating tumor DNA suggested that on-treatment loss of EGFR Exon 19 deletion or L858R mutations, detectable at baseline, correlated with longer PFS, but on-treatment loss of T790M did not. Emergent genetic alterations post progression included C797S, MET amplification, and EGFR amplification. Conclusions: Ramucirumab plus osimertinib demonstrated encouraging safety and antitumor activity in T790M-positive EGFR-mutant NSCLC.
Αρχειοθήκη ιστολογίου
-
►
2023
(138)
- ► Φεβρουαρίου (74)
- ► Ιανουαρίου (64)
-
►
2022
(849)
- ► Δεκεμβρίου (61)
- ► Σεπτεμβρίου (74)
- ► Φεβρουαρίου (65)
-
►
2021
(2936)
- ► Δεκεμβρίου (59)
- ► Σεπτεμβρίου (180)
- ► Φεβρουαρίου (325)
-
▼
2020
(1624)
- ► Δεκεμβρίου (293)
-
▼
Οκτωβρίου
(341)
-
▼
Οκτ 12
(80)
- Medicine by Alexandros G. Sfakianakis
- pubmed: carotid blowout synd...
- pubmed: gene therapies for h...
- ScienceDirect Publication: Biomaterials
- Neurocutaneous melanocytosis (melanosis)
- What is dimethoate used for? Dimethoate is used to...
- Organophosphate Poisoning PDF
- Partial internal biliary diversion
- Biliary ascariasis and severe bacterial outcomes
- The Fussy Baby Network® (FBN), a program supportin...
- Birth Weight and the Development of Functional Gas...
- Low prevalence of infantile functional gastrointes...
- DNA repair targeted therapy
- Plants, Vol. 9, Pages 1350: Identification and An...
- Clinical Genetics
- Intralesional methotrexate
- Intralesional immunotherapy for molluscum contagiosum
- Standardizing a volume benchmark for cerebrospinal...
- Adenomatous neuroendocrine tumors of the middle ea...
- Management of transmodiolar and transmacular cochl...
- Association of Estrogen Receptor 1 and Tumor Necro...
- Primary Intraosseous Squamous Cell Carcinoma Invol...
- Lymphocyte predominant Hodgkin lymphoma, antigen‐d...
- SETDB1 promotes gastric carcinogenesis and metasta...
- Microglia/macrophages express alternative proangio...
- Evaluation of myostatin as a possible regulator an...
- Effect of etelcalcetide on parathyroid hormone sec...
- The role of immune checkpoint inhibitor therapy in...
- Translational perspectives to treat Epidermolysis ...
- Cantilevered resin-bonded fixed partial dentures
- Telomerase reverse transcriptase rs2736098 polymor...
- Cardiac contractility modulation attenuates struct...
- Imaging of bioluminescent Klebsiella pneumoniae in...
- Serum oestradiol levels are inversely associated w...
- Large (stage ≥T2b) and locally advanced renal cell...
- Risk factors for early postoperative recurrence in...
- Immune dysfunction in MGAT2‐CDG
- Cutaneous Manifestations in Adult Patients with CO...
- The Role of Environmental Exposures in Atopic Derm...
- Strategies for having a more effective and less to...
- Mutationssignaturen beim Kopf- und Hals-Tumor
- Frameless stereotactic radiosurgery
- Custom designed radial forearm free flap for recon...
- Spindle Cell Melanoma Presenting as an Ulcer in a ...
- Nummular Headache
- Bleomycin sclerotherapy in lymphangiomas of the he...
- Adjuvant radiotherapy for endometrial cancer with ...
- DDGP vs. SMILE in Relapsed/Refractory Extranodal N...
- Remimazolam in Procedural Sedation With Nonhomogen...
- Evaluation of the Electroglottographic Signal Vari...
- Denosumab induced atypical fracture of free vascul...
- Renal cell carcinoma metastasis to the maxillary b...
- Driveline Infection with Vacuum-Assisted Closure T...
- Conservative Treatment of Iatrogenic Ascending Aor...
- Genome-enabled inference of functional genetic var...
- The Effect of Pituitary Gland Disorders on Glucose...
- Effect of periosteal reaction in medication-relate...
- A combined approach to correct posterior left vent...
- Synonymous mutations and the molecular evolution o...
- Serial circulating tumor DNA in predicting and mon...
- Ramucirumab in Combination with Osimertinib in Adv...
- Lysine-Specific Demethylase-1 Inhibitor CC-90011 i...
- Three distinct stroma types in human pancreatic ca...
- Activity and Safety of Geptanolimab (GB226) for pa...
- Intratumoral Injection of Clostridium novyi-NT Spo...
- Preclinical activity of SAR408701, a novel anti-CE...
- A cyclin D1-dependent transcriptional program pred...
- A Morphometric Study of Stylomastoid Foramen with ...
- The Longissimus Capitis Insertion as a Superficial...
- Advancement of PI3 Kinase Inhibitor Combination Th...
- Preoperative Embolization on Juvenile Nasopharynge...
- Management of Cutaneously Exposed Carotid Stents i...
- IntraOmmaya compartmental radioimmunotherapy using...
- Upper respiratory tract infection
- Behavioural Brain Research
- bioRxiv Subject Collection: Evolutionary Biology
- International Journal of Environmental Research ...
- Antioxidants
-
▼
Οκτ 12
(80)
- ► Σεπτεμβρίου (234)
- ► Φεβρουαρίου (28)
-
►
2019
(13362)
- ► Δεκεμβρίου (19)
- ► Σεπτεμβρίου (54)
- ► Φεβρουαρίου (5586)
- ► Ιανουαρίου (5696)
-
►
2018
(66471)
- ► Δεκεμβρίου (5242)
- ► Σεπτεμβρίου (5478)
- ► Φεβρουαρίου (4835)
- ► Ιανουαρίου (5592)
-
►
2017
(44259)
- ► Δεκεμβρίου (5110)
- ► Σεπτεμβρίου (5105)
-
►
2016
(7467)
- ► Δεκεμβρίου (514)
- ► Σεπτεμβρίου (1038)
- ► Φεβρουαρίου (793)
Αναζήτηση αυτού του ιστολογίου
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
-
Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
-
heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
-
https://ift.tt/2MQ8Ai8
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου
Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.