RESUMO
AIMS: Multiple studies have shown conflicting results on the correlation between the EGFR T790M quantitative level and survival outcomes in osimertinib-treated patients. We sought to validate such correlations using data from an osimertinib early access programme (EAP) providing access for metastatic non-small cell lung cancer patients with limited treatment options. PATIENTS AND METHODS: This observational, multicentre, retrospective analysis included EAP participants who received osimertinib until disease progression, intolerable toxicities or death. Digital droplet polymerase chain reaction-based quantitative plasma genotyping was carried out upon disease progression and data were analysed to explore the relationships between T790M mutant allele fraction (MAF), T790M copy number, MAF ratio and post-osimertinib overall survival. Real-world treatment outcomes and safety were also evaluated. RESULTS: Data from 156 EAP participants were analysed (median follow-up 37.7 months). The median age was 62 years, 62.2% were women, 79.5% were never-smokers, 60.9% had Eastern Cooperative Oncology Group performance status 0/1. In patients with available plasma data (n = 114), T790M MAF (%) showed no significant relationships with overall survival (hazard ratio 1.02; 95% confidence interval 0.99-1.04) or time to treatment discontinuation (TTD) (hazard ratio 1.01; 95% confidence interval 0.98-1.04). Absolute T790M copy number and T790M to activating EGFR mutation MAF ratio also showed no prognostic value. The investigator-assessed response rate was 42.3% and the disease control rate was 85.5%. The median TTD was 15.8 (95% confidence interval 12.5-18.5) months and the median overall survival was 22.3 (95% confidence interval 18.6-26.1) months. CONCLUSION: T790M MAF did not correlate with TTD or overall survival in this EAP cohort but limitations should not be overlooked. Observed survival outcomes and the toxicity profile were consistent with data from other real-world series.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Acrilamidas , Alelos , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Mutação , Estudos RetrospectivosRESUMO
OBJECTIVES: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC. MATERIALS AND METHODS: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). RESULTS: Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPSâ¯≥â¯50%, 1232 (52%) had PD-L1 TPSâ¯≥â¯1%, and 1136 (48%) had PD-L1 TPSâ¯<â¯1%. The most common reason for not having PD-L1 data (nâ¯=â¯249) was insufficient tumor cells (<100) on the slide (nâ¯=â¯170 [6%]). Percentages of patients with PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1%, respectively, were 27% and 53%. CONCLUSIONS: This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations.
Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Expressão Gênica , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prevalência , Estudos RetrospectivosRESUMO
AIMS: Almost all patients with epidermal growth factor receptor (EGFR) mutations will develop resistance to first-line EGFR tyrosine kinase inhibitors (TKIs). The management of oligoprogression on EGFR TKI is controversial. Irradiating progressing tumours may potentially eradicate the resistant clone and allow continuation of EGFR TKI, but the clinical data remain sparse. We aimed to assess the effect of radiotherapy on survival outcomes in patients with oligoprogression in a matched-cohort study. MATERIALS AND METHODS: This was a retrospective matched-cohort study comparing patients with EGFR mutation-positive stage IV non-small cell lung cancer receiving radiotherapy versus chemotherapy for progression. Patients in the radiotherapy group received radiotherapy (mainly stereotactic ablative radiotherapy) for oligoprogression, whereas the chemotherapy group received only systemic chemotherapy upon progression. Key prognostic factors including gender, age, performance status, time to first progression and mutation subtypes were matched. RESULTS: Twenty-five patients with oligoprogression (radiotherapy group) were identified, and a matched chemotherapy group with the same number of patients was generated. The median duration of follow-up was 24.3 and 34 months for the radiotherapy and chemotherapy groups, respectively. The median overall survival of the radiotherapy group was significantly longer than the chemotherapy group, 28.2 versus 14.7 months (P = 0.026). The median progression-free survival (PFS) was 7.0 and 4.1 months after radiotherapy and chemotherapy, respectively (P = 0.0017). The use of radiotherapy was an independent predictive factor of overall survival and PFS in multivariate analysis. Only one patient had ≥grade 3 toxicity after radiotherapy. The frequency of secondary T790M mutation and subsequent Osimertinib exposure were similar in both groups. CONCLUSION: Radiotherapy may effectively extend EGFR TKI therapy for patients with oligoprogression on TKI. Improved PFS and overall survival were observed, although potential biases should not be overlooked. Further randomised studies are warranted.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Projetos de Pesquisa , Estudos Retrospectivos , Análise de SobrevidaRESUMO
OBJECTIVE: To compare interface pressure (IP) and static stiffness index (SSI) of four different compression systems currently in use for the treatment of patients with venous leg ulcer. METHOD: Fifty-two ambulatory adults with healthy legs were recruited at random at a study centre after they had consented. The evaluated systems were: short-stretch system (SSB), Rosidal sys (Lohmann & Rauscher), multilayer bandaging (LSB) Profore (Smith & Nephew), Vari-stretch (VSB) ProGuide (Smith & Nephew) and tubular compression (CS) Rosidal Mobil (Lohmann & Rauscher). Interface pressure was measured using Kikuhime (Harada Corp.), placing a 3 cm-diameter probe at the B1 point. IP recording took place in the supine and standing positions, while sitting and during walking, on application of the compression systems and every 15 minutes thereafter for 4 hours. RESULTS: The IPs of SSB, LSB and VSB, measured immediately after bandage application, were significantly higher than that of CS (all p < 0.05). During the 4-hour study period, the IP for both VSB and LSB measured in the supine position initially increased to > 60 mmHg. Their overall mean IPs in the supine position were 48.96 ± 3.99 mmHg and 48.12 ± 4.57 mmHg, respectively. SSB and CS demonstrated more tolerable IP levels in this position of < 40 mmHg, which was similar to those when sitting. All systems maintained at least 40 mmHg in walking. SSB had a high SSI of 20 throughout the study. LSB followed with an SSI of 18 at the start, which reduced to 13, while the SSI for VSB decreased from 17 to 12 and CS, with an SSI of 6, lagged behind. CONCLUSION: These results may contribute to the understanding of IP and SSI of the four different compression systems evaluated. The IP and SSI data presented give clinicians an indication of the appropriate frequency of re-application of compression, and preliminary data on choosing a safe and effective compression treatment for their patients. DECLARATION OF INTEREST: The investigators received an educational grant from Lohmann & Rauscher GmbH & Co KG for this study.