ABSTRACT
BACKGROUND: This study evaluates the efficacy of osimertinib for the treatment of previously epidermal growth factor receptor tyrosine kinase inhibitors (EFGR-TKI) treated non-small cell lung cancer (NSCLC) patients. METHOD: Research articles reporting the efficacy of osimertinib for NSCLC patients were identified from literature databases (Embase, Ovid, PubMed and Scopus) by following pre-determined eligibility criteria. Response and survival data were extracted from study reports and were pooled under random-effects model to obtain overall/subgroup effect sizes of selected efficacy outcomes. RESULTS: Nine studies (950 patients; age 60.1 years [95% confidence interval: 57.2, 63.1]; 65% [95% CI: 62, 69] females; 69% [35, 100] with T790M; 61% [53, 68] with ex19del; and 35% [29, 41] with L858R mutations). Osimertinib treatment was associated with a PFS of 11.17 months [7.80, 14.55] which was longer in treatment-naïve (20.30 [15.37, 25.23]) than in prior EGFR-TKI-treated (10.20 [9.60, 10.80]) patients. 1-year survival was 81.29% [73.25, 89.32]. Complete response rate was 1.48% [1.19, 1.76]. PR was achieved in 53.18% [24.18, 82.18] patients which differed between treatment-naïve and prior EGFR-TKI-treated patients (74.48 [65.59, 83.37] and 67.99% [62.68, 73.30], respectively. Objective response rate and disease control rates were 69.80% [64.84, 74.77] and 92.43% [89.42, 95.43], respectively, which did not differ between treatment-naïve and prior EGFR-TKI-treated patients. CONCLUSION: Osimertinib treatment yields approximately 10 months PFS in prior EGFR-TKI-treated and 20 months in treatment-naïve NSCLC patients. Partial response rate is also higher in treatment-naïve patients. However, objective response rate (ORR) and disease control rate (DCR) did not differ between groups of patients.
Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Drug Resistance, Neoplasm/genetics , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Survival Rate , Treatment OutcomeABSTRACT
Two-dimensional gel electrophoresis (2DE) is an important tool for investigating the complexity of snake venom proteomes. Apart from applications based on whole proteome analysis, we suggest that 2DE can be used as an assay to guide the progress of protein purification. The aim of this study was to prove the feasibility of this concept by using it to purify rhodocetin from Calloselasma rhodostoma venom. Rhodocetin (α subunit) spot on the 2DE profile of C. rhodostoma venom was first identified and confirmed by mass spectrometry, with a molecular mass of 16 kDa and calculated pI of 5.16. Rhodocetin was subsequently purified by successive anion-exchange and gel filtration chromatography. Every peak from both chromatography profiles was collected and tested on 2DE. The presence of rhodocetin (α subunit) spot in the 2DE profile of the peak DP2 indicated the presence of the protein. The purified compound was used to spike the crude venom. A spiked spot with a 1.6-fold increase in intensity was observed and its position matched to that of rhodocetin (α subunit) on the 2DE profile. Together, these spots confirmed the identity of the purified compound as rhodocetin. Hence, our results have demonstrated the effectiveness of the concept we now term 2DE-guided purification.(AU)
Subject(s)
Animals , Electrophoresis, Gel, Two-Dimensional/methods , Electrophoresis, Gel, Two-Dimensional/veterinary , Proteome/analysis , Proteome/pharmacology , Snake VenomsABSTRACT
Two-dimensional gel electrophoresis (2DE) is an important tool for investigating the complexity of snake venom proteomes. Apart from applications based on whole proteome analysis, we suggest that 2DE can be used as an assay to guide the progress of protein purification. The aim of this study was to prove the feasibility of this concept by using it to purify rhodocetin from Calloselasma rhodostoma venom. Rhodocetin (α subunit) spot on the 2DE profile of C. rhodostoma venom was first identified and confirmed by mass spectrometry, with a molecular mass of 16 kDa and calculated pI of 5.16. Rhodocetin was subsequently purified by successive anion-exchange and gel filtration chromatography. Every peak from both chromatography profiles was collected and tested on 2DE. The presence of rhodocetin (α subunit) spot in the 2DE profile of the peak DP2 indicated the presence of the protein. The purified compound was used to spike the crude venom. A spiked spot with a 1.6-fold increase in intensity was observed and its position matched to that of rhodocetin (α subunit) on the 2DE profile. Together, these spots confirmed the identity of the purified compound as rhodocetin. Hence, our results have demonstrated the effectiveness of the concept we now term 2DE-guided purification.(AU)