Targeted therapy in lung cancer —ASCO 2019 update

SummaryNew targeted therapies for patients with non small cell lung cancer were presented at this year ’s ASCO.EGFR exon 20 insertions might soon be treatable with TAK-788, which showed an objective response rate (ORR) of between 25 and 56% with a disease control rate (DCR) between 67 and 100% depending on the presence or absence of brain metastases at baseline. Capmatinib and tepotinib showed durable responses inMET exon 14 mutations as presented in the phase II GEOMETRY trial and the VISION trial. The median duration of response (DOR) was 9.7 months with a median progression free survival (PFS) of 5.42 months in pretreated patients and 11.14 months respective 9.6 months in those receiving capmatinib in the frontline setting. Tepotinib showed similar results with a median DOR of 12.4 months and a DCR of 66.7%. ForRET-fusion lung cancer the well tolerated RET inhibitor BLU-667 has already been granted breakthrough therapy designation. Among previously treated patients an ORR of 58% and a DCR of 96% was reported. The median duration of response had not yet been reached, with many patients continuing to respond for longer than 24 months. For the large and hard-to-treat group of patients withKRAS-mutated lung cancer, early data on the covalent irreversible inhibitor of theKRASG12C-mutant kinase AMG 510 were presented. In pretreated patients AMG 510 achieved a 50% response rate, with a duration of treatment from 7.3 to 27.4 weeks. Furthermore, AMG 510 has been safe and well...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research

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Authors: Sartore-Bianchi A, Pizzutilo EG, Marrapese G, Tosi F, Cerea G, Siena S Abstract Introduction: Gene fusions are strong driver alterations in various cancers, increasingly diagnosed with multiple testing techniques. ROS1 fusions can be found in 1-2% of non-small cell lung cancer (NSCLC) and several tyrosine kinase inhibitors (TKIs) have been tested in this oncogene-driven disease. NTRK fusions are characteristic of a few rare types of cancer, also infrequently seen in some common cancers including NSCLC. Entrectinib is a newer ROS1 and NTRK inhibitor developed across different tumour types harbouring rearran...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
This study investigated the current management and outcomes of newly diagnosed NSCLC patients with BM in Japanese clinical practice, focusing on their driver mutation status. PATIENTS AND METHODS: We enrolled newly diagnosed, treatment-naïve NSCLC patients with BM between January 2012 and December 2015 from 4 institutions in Japan. The medical records of each patient were retrospectively reviewed, and the treatment details and outcomes were evaluated. RESULTS: In total, 203 patients with BM were enrolled in this study and 73 (36%) were neurologically symptomatic. Regarding initial treatment, 110 patients (54...
Source: Oncology - Category: Cancer & Oncology Authors: Tags: Oncology Source Type: research
(St. Michael's Hospital) A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St. Michael's Hospital of Unity Health Toronto and Harvard Medical School.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Authors: Choo JR, Soo RA Abstract INTRODUCTION: The treatment of lung cancer has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) that target sensitizing somatic (gene) activations including anaplastic lymphoma kinase (ALK)-rearrangements. Despite remarkable initial responses, patients develop progressive disease via various resistance mechanisms, some of which are ALK dependent. Various next-generation ALK TKIs have been developed to improve on central nervous system (CNS) activity and also target the multitude of acquired resistance mechanisms. Of these, lorlatinib has the greatest s...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
Rearrangements in ROS1 oncogene, reported in 1 –2% of patients with non-small cell lung cancer (NSCLC), define a separate molecular sub-group of NSCLC [1]. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with the ability to cross the blood-brain barrier and have sub-nanomolar enzymatic efficacy in ta rgeting rearrangements in ALK and ROS1 [2]. ROS1 G2032R has been reported as the most commonly acquired mutation that mediates resistance to crizotinib therapy [3–5]; however, mechanisms that mediate lorlatinib resistance among patients with ROS1 rearrangement are rarely reported.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
This study is a multicenter, prospective, single ‐arm, phase II clinical study, and explores the efficacy and tolerability of SRS with anlotinib in NSCLC patients with limited brain metastases. The aim of the study is to provide new treatment options for NSCLC patients with brain metastases.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: STUDY PROTOCOL Source Type: research
Justin F. Gainor Rearranged during transfection proto-oncogene (RET) fusions represent a potentially targetable oncogenic driver in non-small cell lung cancer (NSCLC). Imaging features and metastatic patterns of advanced RET fusion-positive (RET+) NSCLC are not well established. Our goal was to compare the imaging features and patterns of metastases in RET+, ALK+ and ROS1+ NSCLC. Patients with RET+, ALK+, or ROS1+ NSCLC seen at our institution between January 2014 and December 2018 with available pre-treatment imaging were identified. The clinicopathologic features, imaging characteristics, and the distribution of met...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Authors: Nakashima K, Demura Y, Oi M, Tabata M, Tada T, Shiozaki K, Akai M, Ishizuka T Abstract We herein report a 66-year-old woman with advanced lung adenocarcinoma (PD-L1 tumor proportion score 60%) lacking driver oncogenes in whom meningeal carcinomatosis, along with sudden onset dizziness, deafness, and consciousness disturbance, appeared after second-line chemotherapy. Whole-brain radiation therapy (WBRT) and Pembrolizumab were subsequently administered, and third-line chemotherapy with Pembrolizumab is now ongoing. At the time of writing, the patient has achieved a 23-month survival without disease progressi...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Among patients with non-small cell lung cancer (NSCLC), it is estimated that between 3 –5% have anaplastic lymphoma kinase (ALK)-positive disease [1] and 1.7–2.2% have ROS1 gene rearrangement [2–4]. Targeting ALK using tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of patients with ALK-rearranged NSCLC [5]. However, most patients relapse on first or se cond-generation ALK TKI therapy within months to a few years following acquired resistance [6–8]. The third-generation ALK and ROS1 inhibitor lorlatinib (PF-06463922) was developed to inhibit resistant ALK mutations, includi...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
In conclusion, combining MTX with coconut oil in a NE had improved its efficacy while ameliorating its oxidative stress effect on the brain and lungs. PMID: 32133872 [PubMed - in process]
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research
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