BACKGROUND/AIMRegorafenib is an oral multikinase inhibitor used in later lines for metastatic colorectal carcinoma (mCRC) treatment, but its efficacy and tolerability are low. To improve the response rates and ameliorate adverse effects, different strategies have been implemented. In our study, we examined the effect of statin usage in patients with mCRC treated with regorafenib.PATIENTS AND METHODSThis single-center retrospective study included patients with mCRC who were treated with regorafenib between January 2015 and December 2023. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were adverse effects and the tolerability of regorafenib.RESULTSThe data of 105 patients were collected retrospectively. The median age of the patients was 66 years, and 60 patients were male. Seventeen patients (16.1%) were receiving statins. Statin-using patients were significantly older than non-users (72 years vs. 66.5 years, p=0.05). Comorbid diseases were more common in patients using statins. The median PFS was 1.9 months for statin users and 4.2 months for statin non-users (p<0.001), and the median OS was 4.7 vs. 6.7 months (p=0.01). Cox regression revealed that statin usage was significantly associated with a higher hazard ratio (HR) for PFS (2.53) and OS (2.06) (both p<0.01 and p=0.02, respectively).CONCLUSIONStatins are associated with decreased survival and response rates in patients with mCRC treated with regorafenib. However, further studies are needed to confirm these results.

01 Oct 2024·The Lancet Respiratory Medicine

Nintedanib for patients with lymphangioleiomyomatosis: a phase 2, open-label, single-arm study

Article

Author: Vasco, Chiara ; Trevisan, Roberta ; Pelosi, Giuseppe ; Zompatori, Maurizio ; Torre, Olga ; Elia, Davide ; Luisi, Francesca ; Specchia, Claudia ; Caminati, Antonella ; Cassandro, Roberto ; Harari, Sergio ; Geginat, Jens

BACKGROUNDLymphangioleiomyomatosis is an ultra-rare disease mainly affecting women of childbearing age. The MILES trial showed the efficacy of sirolimus, an mTOR inhibitor, in stabilising lung function in patients with lymphangioleiomyomatosis. Drug toxicity and development of resistance are potential limitations of therapy with sirolimus. Nintedanib is a multikinase inhibitor that inhibits PDGFR, which is active in human and murine lymphangioleiomyomatosis lesions. We aimed to investigate the activity and safety of nintedanib in patients with lymphangioleiomyomatosis.METHODSThis phase 2, open-label, single-arm study was conducted at MultiMedica IRCCS, a national referral university centre for rare pulmonary diseases in Milan, Italy. Eligible participants were aged 18 years and older and had sporadic or tuberous sclerosis complex-associated lymphangioleiomyomatosis with progressive pulmonary function decline in the past year despite treatment with sirolimus or treatment naive. Patients received nintedanib 150 mg orally twice per day, with a possible reduction to 100 mg twice per day in case of side-effects or hepatoxicity, for 12 months, followed by a period of 12 additional months without study treatment. The primary endpoint was the change in FEV₁ (FEV₁ slope in L) over 12 months. This study is registered with ClinicalTrials.gov, NCT03062943.FINDINGSFrom Oct 14, 2016, to Dec 13, 2019, 35 female patients (mean age 50 years [SD 11]) entered the study, 30 of whom were eligible and received nintedanib. After 12 months, 22 patients completed the treatment, 19 of whom also completed the 12 months of follow-up. FEV₁ remained stable after one year of treatment (predicted mean difference 0·001 L [95% CI -0·063 to 0·066]; p=0·97). During the 12 months off treatment, a slight decline in FEV₁ was observed (predicted mean difference -0·076 L [95% CI -0·149 to -0·004]; p=0·040). The most frequent adverse events were nausea (15 [50%] patients), diarrhoea (eight [26%]), and abdominal pain (two [7%]). No serious adverse events were observed during the treatment period.INTERPRETATIONOur findings suggest that nintedanib did not improve FEV₁, but that the treatment was generally well tolerated. These results might support nintedanib as a second-line therapy in patients not controlled by standard treatment with mTOR inhibitors. Further investigation, such as a non-inferiority trial comparing nintedanib and sirolimus could help to better clarify the role of this drug as a potential alternative treatment.FUNDINGBoehringer-Ingelheim.

Signal Transduction and Targeted Therapy

Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial

Article

Author: Lin, Hai-Feng ; Yao, Ji-Cheng ; Chen, Li-Ming ; Hu, Xiao-Hua ; Zhou, Ze-Qiang ; Zhou, Hua-Qiang ; Pan, Suo-Ming ; Zheng, Xin ; Lin, Ying-Cheng ; Zhang, Jian ; Zhang, Ya-Xiong ; Lei, Xiao-Lin ; Zhang, Li ; Chen, Jian-Hua ; Yu, Qi-Tao ; Lan, Bin ; Kong, Tian-Dong ; Chen, Gang ; Li, Feng ; Wu, Guo-Wu ; Wu, Di ; Wang, Zi-Bing ; Zhang, Hua ; Zhu, Jun-Fei ; Fang, Wen-Feng

AbstractDual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

100 Deals associated with immunokinase inhibitor(Angex Pharmaceutical)

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Indication	Highest Phase	Country/Location	Organization	Date
Liver Cancer	IND Approval	US	Angex Pharmaceutical, Inc.Startup	12 Jun 2024

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