9542 Background: Currently there is an intense debate concerning therapeutic strategies in EGFR positive NSCLC patients with advance disease. Osimertinib is superior to standard EGFR Tyrosine Kinase Inhibitors (TKIs) as first line treatment. However, it is yet unclear whether this option is superior to sequential treatment of a 1st or 2nd generation TKI followed by osimertinib. In order to clarify this issue it is important to identify which patients are at high risk of progression disease. Methods: This is a prospective, multicentre, cross-sectional study promoted by Spanish Lung Cancer Group. 698 plasma samples from 196 advanced NSCLC patients with tumors harboring an EGFR activating mutation and treated with a first line TKI (afatinib, gefitinib, erlotinib or osimertinib) were analyzed. Plasma samples were prospectively collected before treatment (T0), after 3 months of treatment (T3), after 6 months of treatment (T6) and at first disease progression. EGFR mutations were analyzed by dPCR. Multivariate Cox proportional hazards analysis was used to determine the significance of ctDNA in the prediction of prognosis. Results: The median follow up was 19.8 months. At baseline patients with plasma EGFR sensitizing mutations at allele frequency (AF) ≥ 10% had worse OS and PFS than patients in which the opposite occurred (HR = 1.86; 95 %CI: 1.09-3.17, and HR = 1.65; 95 %CI: 1.07-2.58, respectively). Noteworthy, median OS and PFS time were 18.6 and 8.8 months respectively, in patients with plasma AF≥10% before treatment initiation compared to 37.9 and 12.4 months for patients with plasma AF < 10%. Similar results were obtained when a cutoff of AF≥ 5% was used (HR = 1.73; 95%CI: 1.02-2.94 for OS, and HR = 1.72; 95%CI: 1.13-2.61 for PFS). Patients who remained ctDNA-positive after 3 months of treatment exhibited also poorer outcomes (HR = 3.24; 95%CI: 1.77-5.94 for OS, and HR = 3.1; 95%CI: 1.91-5.03 for PFS). In the same way, detectable levels of ctDNA after 6 months of treatment predicted shorter OS and PFS (HR = 3.3; 95%CI: 1.53-7.13 and HR = 2.62; 95%CI: 1.62-4.25, respectively). Conclusions: ctDNA levels significantly predict survival. Moreover, ctDNA levels before treatment initiation can be useful to assess patient’s progression risk which is not possible to assess otherwise facilitating treatment decision making.
Vesicoureteral reflux (VUR) after renal transplantation in adult patients has been reported. In renal transplant recipients, symptomatic urinary tract infection can cause high morbidity despite improved immunosuppressive and antibiotic treatment. In our country there have been few reported cases about use of copolymer of dextranomer and hyaluronic acid (DX-HA) injection in a renal transplant. We present 3 cases of recurrent or complicated infections with evidence of high-grade VUR, which were treated with DX-HA. Only 1 case had a partial remission; however, there were no episodes of urinary tract infection in 12 months of follow-up. Suburethral injection is an endoscopic treatment modality with low morbidity in our country.
e21515 Background: The liquid biopsy (LB) is an important tool in the diagnostic and follow up of the patients with non-small cell lung cancer (NSCLC) and can provide big information about the mutational variability of the disease during of the treatment. Methods: We conducted a multicenter study with 200 patients with EGFR-mutated NSCLC, treated with first-line TKI therapy. We analyse the ctDNA by dPCR pre-treatment, at 8 weeks, at 7 months and at the progression of the disease (PD). Results: A total of 200 patients (60% women / 40% men) were included. The median of age was 68-year. The never smokers were 56% and 34% ex-smokers. 92% of the cases were adenocarcinomas. According to the stage of the disease, 52% were stage IVB, 38.5% stage IVA and 9.5% unknown. The first-line treatment was afatinib in 47.5%, erlotinib in 21.5% and gefitinib in 31%. According to the type of sensitivity mutation, 61.5% corresponded to Del19, 32% to L858R, 2.5% to G719X and 2.5% to L861Q. At the time of diagnosis, 63% had pulmonary metastatic involvement and 42.5% liver metastasis. At the time of data analysis, 66% of the patients had some progression of the disease (PD) and 37% died. 68% of the patients with Del19 received afatinib, while 20% of the patients with L858R received afatinib, 54.5% erlotinib and 32% gefitinib (p = 0.02). With a median follow-up of 20 months, progression-free survival was 11.8 months, without any differences according to the treatment (p = 0.93). The groups with worse PFS included: the squamous histology (HR 5.7; 95%CI 2.04-15.91, p = 0.001), the G719X mutation (HR 3.36; 95%CI 1.21-9.25, p = 0.019) and the liver metastasis (HR 1.65; 95%CI 1.01-2.68, p = 0.042). The sensitizing mutation was detected in the 80.8% of the patients in the LB by dPCR and the T790M in 2%. However, in the first control only was detectable in 18.5%. At the time of PD, the percentage of detection of T790M raised to 52.3%, and the sensitizing mutation 79.44%. At that moment, patients who developed T790M were mostly never smokers (66%, p = 0.006) and had Del19 (66%). Patients with bone progression developed T790M in 60.4% (p = 0.014) and hepatic 27% (p = 0.012). Conclusions: We concluded that the clinical characteristics of the patients of the OPH study are consistent with the previous reported in the Caucasian population and the subgroups with the worst prognosis include the squamous histology, the G719X mutation and the liver metastasis.
e17043 Background: Checkpoint Inhibitors (CPI) have become a new standard of treatment in advanced urothelial carcinoma. However, little is known regarding the outcome of patients in daily practice.We aimed to assess tumor response and toxicity of CPIs in a cohort of patients treated in “real world” conditions. In parallel, a comprehensive molecular study in tumor samples from these patients, is ongoing. Methods: We designed an observational retrospective study within the “Grupo Centro” collaborative group. Adult patients diagnosed of metastasic urothelial carcinoma (mUC) and treated with CPIs between 2011-2019 in any of the 20 centers of the group, were eligible. Results: Up to date 100 patients have been included (82% males) with a median age of 74 years (48 -96). In 82% patients primary was bladder cancer. Most common metastasic sites were bone (26%) and liver (16%).With a median follow up of 10,6 months(mo) median progression free survival (mPFS) was 6,6mo (1,4-95,4 range) and median Overall Survival (mOS) was 21.3mo (3,8-121,8). 38% of patients received CPIs in first line(L): atezolizumab:27, pembrolizumab: 10, nivolumab:1. The median number of cycles was 8,2. Up to 51% received platinum-based combinations in first line. 69% (69/100) pts received 2L treatment: 68% with CPIs, 27,5% with chemotherapy and 4% with FGFR inhibitors (as part of a clinical trial). 2L mPFS was 3,5 mo (1,9-25.9). 23% (23/100) patients received 3L, of them 26% (6/23) were treated with CPIs. 3L mPFS:8,3mo(0,4-43,8). As a whole, patients treated with CPI accross different lines, achieved complete response in 8% of the cases, partial response in 18% and stable disease in 15%. Up to 44% of cases presented progressive disease as best response and evaluation was not available in 15%. Most common G1-2 AEs related to immunotherapy were: asthenia:31%,pruritus:16% and anorexia: 9%.10% pts experienced G3-4 toxicity: asthenia G3: 4, diarrhea G3: 1, erythrodysesthesia G3:1, arthromyalgia G3: 1, cardiac arrest G4:1,pneumonitis G4:1,anemia G3:1. Conclusions: This study confirms the efficacy and security of CPIs in real world. Response rates and toxicity profile were comparable to those reported in clinical trials.
e21196 Background: Non-small cells lung cancer (NSCLC) patients treated with Tyrosine Kinase Inhibitors (TKI) at first-line ultimately develop disease progression after 10 to 14 months. Mechanisms underlying TKI-resistance are not complete understood. Tumor re-biopsy is often unfeasible for NSCLC patients and liquid biopsy is a suitable alternative in identify mechanism by which tumors progress. Methods: 113 plasma samples were collected from advanced stage EGFR positive NSCLC patients upon disease progression according to RECIST V1.1. cfDNA NGS profiling was carried out using the Oncomine™ Pan-Cancer Cell-Free Assay and sequenced on an Ion GeneStudio S5 Plus System. Variant calling and annotation were performed with Torrent Suite and Ion Reporter (v5.16) software, respectively. In addition, we developed a bioinformatic pipeline, using RStudio for variant filtering. Results: Overall, 344 somatic variants were detected with an average number of variants per patient of 2.32 and a median Mutant Allele Frequency (MAF) of 0.83%. Most mutated genes were EGFR (63.72%), TP53 (60.18%), APC (16.81%), MAP2K1 (11.50%), PIK3CA (10.62%), FGFR3 (7.08%), KRAS (7.08%) and BRAF (6.19%). As expected, SNPs were the most frequent mutation type (72.67%), following by INDELs (24.41%) and CNVs (2.91%). We found high co-occurrence between MYC-GNA11, MYC-CCND2, HRAS-AR and EGFR-TP53 genes using Jaccard’s score (0.5, 0.5, 0.5 and 0.46, respectively). Within EGFR-mutated patients, 40% had T790M resistance mutation. Finally, we found KRAS mutations and missense PIK3CA mutations were mutually exclusive. Conclusions: Molecular profiling of liquid biopsies collected upon disease progression using NGS help to identify molecular mechanisms underlying treatment failure.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.