Purpose: This phase II study evaluated the efficacy and tolerability of onvansertib, a polo-like kinase 1 (PLK1) inhibitor, in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab for the second-line treatment of -mutant metastatic colorectal cancer (mCRC).
Patients And Methods: This multicenter, open-label, single-arm study enrolled patients with -mutated mCRC previously treated with oxaliplatin and fluorouracil with or without bevacizumab. Patients received onvansertib (15 mg/m once daily on days 1-5 and 15-19 of a 28-day cycle) and FOLFIRI + bevacizumab (days 1 and 15). The primary end point was the objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), duration of response (DOR), and tolerability. Translational and preclinical studies were conducted in -mutant CRC.
Results: Among the 53 patients treated, the confirmed ORR was 26.4% (95% CI, 15.3 to 40.3). The median DOR was 11.7 months (95% CI, 9.4 to not reached). Grade 3/4 adverse events were reported in 62% of patients. A post hoc analysis revealed that patients with no prior bevacizumab treatment had a significantly higher ORR and longer PFS compared with patients with prior bevacizumab treatment: ORR of 76.9% versus 10.0% (odds ratio of 30.0, < .001) and median PFS of 14.9 months versus 6.6 months (hazard ratio of 0.16, < .001). Our translational findings support that prior bevacizumab exposure contributes to onvansertib resistance. Preclinically, we showed that onvansertib inhibited the hypoxia pathway and exhibited robust antitumor activity in combination with bevacizumab through the inhibition of angiogenesis.
Conclusion: Onvansertib in combination with FOLFIRI + bevacizumab showed significant activity in the second-line treatment of patients with -mutant mCRC, particularly in patients with no prior bevacizumab treatment. These findings led to the evaluation of the combination in the first-line setting (ClinicalTrails.gov identifier: NCT06106308).
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http://dx.doi.org/10.1200/JCO-24-01266 | DOI Listing |
Dermatol Online J
October 2024
Texas A&M School of Medicine, Dallas, Texas, USA.
Exudative (wet) age-related macular degeneration can be treated with the vascular endothelial growth factor (VEGF)-inhibiting monoclonal antibody bevacizumab. Currently, bevacizumab therapy is associated with known skin-related side effects, such as rash, mucosal hemorrhage, and hemorrhagic ulcers. While subungual "splinter" hemorrhage is a documented side effect of VEGF receptor antagonists and Raf protein inhibitors, there are no prior reports of bevacizumab-induced subungual hemorrhage to the best of our knowledge.
View Article and Find Full Text PDFSignal Transduct Target Ther
December 2024
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China.
This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.
View Article and Find Full Text PDFOncologist
December 2024
Department of Oncology, Mayo Clinic, Rochester, MN, United States.
Background: Atezolizumab plus bevacizumab (A/B) received FDA approval as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC) in 2020. However, optimal subsequent treatment options are unclear. Here, we describe clinical outcomes of advanced HCC patients following first-line treatment with A/B.
View Article and Find Full Text PDFEye (Lond)
December 2024
Notal Vision, Manassas, VA, USA.
Background: Investigate retinal fluid changes via a novel deep-learning algorithm in real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD).
Methods: Multicenter, retrospective chart review and optical coherence tomography (OCT) image upload from participating sites was conducted on patients treated with faricimab for nAMD from February 2022 to January 2024. The Notal OCT Analyzer (NOA) algorithm provided intraretinal, subretinal and total retinal fluid for each scan.
Medicine (Baltimore)
December 2024
Department of Radiology, Dong-A University College of Medicine, Busan, Republic of Korea.
Since 2007, the combination of atezolizumab and bevacizumab, comprising an immune checkpoint inhibitor and a molecularly targeted agent, has become the first-line treatment for advanced hepatocellular carcinoma (HCC). Predicting prognosis prior to systemic chemotherapy remains a critical concern. This study included 84 advanced HCC patients who underwent enhanced computed tomography (CT) and Gd-EOB-DTPA magnetic resonance imaging (MRI) before the systemic therapy were included.
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