1.
Combined plasma and tissue genotyping of EGFR T790M benefits NSCLC patients: a real-world clinical example.
Wei, B, Zhao, C, Li, J, Zhao, J, Ren, P, Yang, K, Yan, C, Sun, R, Ma, J, Guo, Y
Molecular oncology. 2019;(5):1226-1234
Abstract
Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a prevalent clinical problem in the management of advanced non-small-cell lung cancer (NSCLC) with TKI-sensitizing mutations in the EGFR gene. Third-generation EGFR-TKIs have demonstrated potent activity against TKI resistance mediated by the EGFR T790M mutation, and standard rebiopsy and liquid biopsy are utilized to assess the T790M status of the NSCLC patients who experienced progressive disease (PD). Here, we conducted a retrospective study to assess 375 patients whose initial biopsy indicated a TKI-sensitizing mutation (either EGFR 19del or L858R) and who developed PD after treatment with first-generation TKIs, and assayed for T790M status. We adopted a combination approach in which tissue rebiopsy is preferred, utilizing liquid biopsies when tissue rebiopsy is not feasible. We analyzed the potential predictive clinical factors affecting T790M detection, evaluated the standard rebiopsy and liquid biopsy methods in T790M genotyping, and reported the clinical performance of osimertinib. Our results suggested that primary EGFR 19del, brain metastasis, and longer progression-free survival of initial EGFR-TKI treatment are associated with acquired T790M resistance. T790M-positive patients significantly benefited from osimertinib. In conclusion, the real-world clinical adoption of the combination approach with both tissue rebiopsy and liquid biopsy for T790M genotyping may provide significant benefits to patients who have developed PD after first-generation TKI treatments.
2.
Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial.
He, M, Li, Q, Zou, R, Shen, J, Fang, W, Tan, G, Zhou, Y, Wu, X, Xu, L, Wei, W, et al
JAMA oncology. 2019;(7):953-960
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Abstract
IMPORTANCE Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study. OBJECTIVE To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion. DESIGN, SETTING, AND PARTICIPANTS This randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months. INTERVENTIONS Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks). MAIN OUTCOMES AND MEASURES The primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment. RESULTS For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]). CONCLUSIONS AND RELEVANCE Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02774187.