Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A retrospective multicenter study

Background Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

Lapatinib as first-line treatment for muscle-invasive urothelial carcinoma in dogs

Epidermal growth factor receptors 1 and 2 (EGFR and HER2) are frequently overexpressed in various malignancies. Lapatinib is a dual tyrosine kinase inhibitor that inhibits both EGFR and HER2. Although a phase III trial failed to show the survival benefits of lapatinib treatment after first-line chemotherapy in patients with EGFR/HER2-positive metastatic urothelial carcinoma, the efficacy of lapatinib for untreated urothelial carcinoma is not well defined. Here, we describe the therapeutic efficacy of lapatinib as a first-line treatment in a canine model of muscle-invasive urothelial carcinoma. In this non-randomized clinical trial, we compared 44 dogs with naturally occurring urothelial carcinoma who received lapatinib and piroxicam, with 42 age-, sex-, and tumor stage-matched dogs that received piroxicam alone. Compared to the dogs treated with piroxicam alone, those administered the lapatinib/piroxicam treatment had a greater reduction in the size of the primary tumor and improved survival. Exploratory analyses showed that HER2 overexpression was associated with response and survival in dogs treated with lapatinib. Our study suggests that lapatinib showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use for untreated advanced urothelial carcinoma in dogs. The use of lapatinib as a first-line treatment may be investigated further in human patients with urothelial carcinoma.

Efficacy of apatinib combined with FOLFIRI in the first-line treatment of patients with metastatic colorectal cancer

SummaryObjective. To evaluate the efficacy and safety of apatinib combined with FOLFIRI in the first-line treatment of advanced metastatic colorectal cancer (mCRC) and explore potential factors of efficacy. Methods. Twenty mCRC patients treated at Affiliated Cancer Hospital of Shanxi Medical University from March 2017 to March 2019 were included according to the enrolment criteria. They provided informed consent and were treated with apatinib combined with FOLFIRI according to the scheduled regimen until disease progression or unacceptable toxicity occurred. The primary endpoint was OS. The secondary endpoints included PFS, ORR, DCRand safety. OS and PFS were calculated using Kaplan–Meier curves. Univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of OS and PFS. R was used to determine cut-off values for biochemical indicators. Forest maps were drawn for Cox univariate results and the relationships between NLR and ECOG, which were significant in univariate analysis, and OS were represented by Kaplan–Meier curves. Results. The median OS and PFS were 16.135 months (95% CI: 9.211–22.929) and 6 months (95% CI: 5.425–6.525). Multivariate Cox analysis showed that NLR and CEA were independent prognostic factors. The most common grade 3–4 adverse events were hypertension, diarrhoea, increased alkaline phosphatase, decreased leukocytes and decreased neutrophils. Conclusion. Apatinib combined with FOLFIRI for the first-line treatment of advanced unresectable mCRC showed good efficacy and safety. The baseline NLR was predictive of efficacy, and a low baseline NLR (HR: 0.2895, P = 0.0084) was associated with improved OS.Clinical Research Registration Number: ChiCTR1800015308.

Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer

Purpose Some patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications. Methods RAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies). Results Twenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test). Conclusion Thirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.