FDA Review of a Panitumumab (Vectibix™) Clinical Trial for First‐Line Treatment of Metastatic Colorectal Cancer

2009 ◽  
Vol 14 (3) ◽  
pp. 284-290 ◽  
Author(s):  
Ruthann M. Giusti ◽  
Martin H. Cohen ◽  
Patricia Keegan ◽  
Richard Pazdur
2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 75-75
Author(s):  
Ke-Feng Ding ◽  
Yue Liu ◽  
Jiaqi Chen ◽  
Lifeng Sun ◽  
Dong Xu ◽  
...  

75 Background: Anlotinib is an oral small molecule multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR1/2/3, FGFR1-4, PDGFR α/β and c-Kit, with a broad spectrum of inhibitory effects on tumor angiogenesis and growth. In a previous trial, Anlotinib had been demonstrated to be safe and efficacious in advanced colorectal cancer after failure of recommended treatment. We aimed to evaluate the efficacy and safety of Anlotinib combined with CAPEOX as first-line treatment for unresectable RAS and BRAF wild-type metastatic colorectal cancer (mCRC). Methods: ALTER-C-002 is a single-arm phase II clinical trial. A total of 30 patients with RAS/BRAF wild-type unresectable mCRC, aged 18-75, without prior systemic treatment and ECOG performance score ≤ 1 will be prospectively included. Patients received Capecitabine (850 mg/m2, p.o., on day 1-14 every 3 weeks), Oxaliplatin (130 mg/m2, i.v., every 3 weeks) and Anlotinib (12 mg, p.o., 2 weeks on/1 week off). After 6 cycles of inducing therapy, patients will receive Capecitabine and Anlotinib as maintenance therapy until tumor progression. Primary endpoint was objective response rate (ORR); secondary endpoints included safety, disease control rate (DCR) and progression-free survival (PFS). Results: As of Sep.15th, 2020, 19 patients had been enrolled. 12 of 19 patients were evaluable for antitumor activity: 10 patients had partial response, 2 patients had stable disease. The ORR was 83.3% (95% CI: 51.6–97.9%), and DCR was 100% (95% CI: 73.5–108.1%). 9 patients (47.4%) developed grade Ⅲ adverse events with 1 (5.3%) grade Ⅳ AE. The grade Ⅲ AEs included hypertension (n = 8), diarrhea (n = 3), hypertriglyceridemia (n = 2), leukopenia and neutropenia (n = 3), alanine aminotransferase increase (n = 1), intestinal obstruction (n = 1), nausea and vomiting (n = 1), and grade Ⅳ AE was blood bilirubin increase. 1 patient received emergent surgery for relieving intestinal obstruction after 14 days of Anlotinib treatment discontinuation. No extra bleeding or wound healing risk were observed during the perioperative period. No treatment-related deaths occurred. Conclusions: The combination of Anlotinib and CAPEOX displayed promising antitumor activity and manageable toxicity in unresectable RAS and BRAF wild-type mCRC, which should be merited further evaluation in randomized studies. Clinical trial information: NCT04080843.


2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.


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