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Mashup Score: 6
AbstractBackground:. Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of 5′-AMP-activated protein kinase (AMPK) suggesting combination therapy may enhance antitumor activity of sapanisertib. We report preliminary safety, tolerability, and efficacy from the dose-escalation study of sapanisertib in combination with metformin in patients with advanced solid tumors.Methods:. Patients with advanced metastatic solid tumors resistant or refractory to standard treatment, with and without mTOR/AKT/PI3K pathway alterations, received sapanisertib 3 or 4 mg daily together with metformin once to three times daily (500–1,500 mg). All patients underwent 14-day titration period for metformin in cycle 1. Tumor measurements were performed following cycle 2 and subsequently every 8 weeks.Results:. A total of 30 patients were enrolled across four cohorts (3 mg/500 mg; 3 mg/1,000 mg
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 11
Novel tissue-agnostic therapeutics targeting driver mutations in tumor cells have been recently approved by FDA, driven by basket trials that have demonstrated their efficacy and safety across diverse tumor histology. However, the relative rarity of primary brain tumors (PBTs) has limited their representation in early trials of tissue-agnostic medications. Thus, consensus continues to evolve regarding utility of tissue-agnostic medications in routine practice for PBTs, a diverse group of neoplasms characterized by limited treatment options and unfavorable prognoses. We describe current and potential impact of tissue-agnostic approvals on management of PBTs. We discuss data from clinical trials for PBTs regarding tissue-agnostic targets, including BRAFV600E, neurotrophic tyrosine receptor kinase (NTRK) fusions, microsatellite instability (MSI), mismatch repair deficiency (dMMR), and high tumor mutational burden (TMB-H), in context of challenges in managing PBTs. Described are additional
Source: www.cell.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 10
PURPOSE Human epidermal growth factor receptor 2 (HER2) is an effective therapeutic target in breast and gastric and gastroesophageal junction cancers. However, less is known about the prevalence of ERBB2 (HER2) amplification and the efficacy of HER2-targeted treatment in other tumors. PATIENTS AND METHODS We assessed HER2 amplification status among 5,002 patients with advanced disease (excluding breast cancer) who underwent next-generation sequencing. We evaluated the clinical benefit of HER2-targeted therapy by measuring the time-dependent overall survival (OS) from the genomic testing results, progression-free survival (PFS), and PFS during HER2-targeted therapy (PFS2) compared with PFS during prior therapy (PFS1). RESULTS Overall, 122 patients (2.4%) had HER2 amplification, including patients with endometrial (5.3%), bladder (5.2%), biliary or gallbladder (4.9%), salivary (4.7%), and colorectal cancer (3.6%). Forty patients (38%) with nongastric, nongastroesophageal junction, or no
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 2
PURPOSE To study whether BRAF V600 mutations in non–small-cell lung cancer (NSCLC) may indicate sensitivity to the BRAF inhibitor vemurafenib, we included a cohort of patients with NSCLC in the vemurafenib basket (VE-BASKET) study. On the basis of observed early clinical activity, we expanded the cohort of patients with NSCLC. We present results from this cohort. METHODS This open-label, histology-independent, phase II study included six prespecified cohorts, including patients with NSCLC, and a seventh all-comers cohort. Patients received vemurafenib (960 mg two times per day) until disease progression or unacceptable toxicity. The primary end point of the final analysis was objective response rate (Response Evaluation Criteria in Solid Tumors, version 1.1). Secondary end points included progression-free survival, overall survival, and safety. Because the prespecified clinical benefit endpoint was met in the initial NSCLC cohort, the cohort was expanded. RESULTS Sixty-two patients wit
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 2
Purpose Parallel activation of the phosphatidylinositol 3-kinase–mammalian target of rapamycin pathway represents a mechanism of primary and acquired resistance to BRAF-targeted therapy, but the two pathways have yet to be cotargeted in humans. We performed a phase I study to evaluate the safety and activity of the BRAF inhibitor vemurafenib in combination with the mammalian target of rapamycin inhibitor everolimus in BRAF-mutated advanced solid tumors. Patients and Methods We performed a 3+3 dose-escalation study with escalating doses of both oral (PO) vemurafenib administered twice a day and PO everolimus administered daily. Results Twenty patients with advanced cancers were enrolled. The median adult age was 64 years (range, 17 to 85 years); two pediatric patients were 10 and 13 years old. Patients were heavily pretreated with prior BRAF or MEK inhibitors (n = 11), phase I clinical trial therapy (n = 10), surgery (n = 18), radiation therapy (n = 11), and chemotherapy (n=13). One of
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 1Activity of Brigatinib in Crizotinib and Ceritinib-Resistant ROS1- Rearranged Non–Small-Cell Lung Cancer - 7 hour(s) ago
One to two percent of non–small-cell lung cancers (NSCLCs) harbor ROS1 gene rearrangements. 1 – 3 ROS1 gene rearrangement leads to constitutive activation receptor tyrosine kinase that activates downstream mitogen-activated protein kinase, phosphoinositide-3 kinase, signal transducer and activator of transcription 3, and other pathways leading to oncogenesis. 4 Because ROS1 shares 49% amino acid sequence homology with anaplastic lymphoma kinase (ALK) in the kinase domain, ROS1 rearranged (ROS1 -positive)
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 0
Solid pseudopapillary neoplasms (SPNs) of the pancreas are exocrine neoplasms that predominantly affect young females and are considered to have low malignant potential. Surgical resection offers patients an excellent chance of long-term survival, even in cases of local invasion, recurrence, and metastatic disease. 1 – 3 Recent studies have demonstrated that invasion of these neoplasms into muscular vessels, advanced tumor stage by European Neuroendocrine Tumors Society classification, and distant
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 29Exceptional Responses to Selpercatinib in RET Fusion–Driven Metastatic Pancreatic Cancer - 7 hour(s) ago
Financial support: Jie Wu, Jie Wu Administrative support: Vivek Subbiah, Vivek Subbiah Provision of study materials or patients: Sireesha Yedururi, Vivek Subbiah, Sireesha Yedururi, Vivek Subbiah Collection and assembly of data: Vivek Subbiah, Vivek Subbiah Data analysis and interpretation: Deepak Bhamidipati, Jason Huse, Sri Veda Chinapuvvula, Jie Wu, Deepak Bhamidipati, Jason Huse, Sri Veda Chinapuvvula, Jie Wu AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 4
Medullary thyroid cancer (MTC) is a neuroendocrine tumor that originates from the parafollicular cells (or C cells) of the thyroid gland and account s for 1% to 2% of thyroid cancers in the United States. 1 The CNS is a rare site of metastasis in MTC, with < 15 cases reported in the medical literature; however, the prevalence may be underreported because of the infrequent use of CNS imaging in patients with MTC. 1, 2 The optimal treatment approach for patients with MTC with CNS involvement is currently
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 0
We present a case showing intracranial efficacy of pemigatinib in pilocytic astrocytoma with FGFR1 N546K mutation
Source: ascopubs.orgCategories: General Medicine News, Hem/OncsTweet
⭐️Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies @AACR @CCR_AACR @CRC_AACR https://t.co/WvTjvgNftP