RESUMO
OBJECTIVES: The MYLUNG (Molecularly Informed Lung Cancer Treatment in a Community Cancer Network) consortium pragmatic study assessed real-world biomarker testing rates and turnaround times within a large community-based oncology network. MATERIALS AND METHODS: This retrospective observational chart review study investigated patients with mNSCLC initiating first-line (1L) systemic therapy between 01-April-2018 and 31-March-2020. Biomarker testing rates and timing relative to 1L therapy for EGFR, ALK, ROS1, BRAF, and PD-L1 were assessed, including use of next-generation sequencing (NGS). RESULTS: Among 3474 adults: 74% had adenocarcinoma and 76% had a documented ECOG performance status of 0 or 1. Ninety percent had testing for at least one biomarker, and 46% received all 5 biomarker tests. Changes in testing rates from 2018 to 2020 were 71% to 71% for EGFR, 71% to 70% for ALK, 69% to 67% for ROS1, 51% to 59% for BRAF, 82% to 84% for PD-L1, and 42% to 49% for all 5 biomarkers. NGS testing increased from 33% to 45% (p < 0.0001). Median time from mNSCLC diagnosis to 1L therapy was 35 days. Median turnaround times from biomarker testing orders to results ranged from 10 to 15 days for the individual biomarkers and 18 days for NGS. CONCLUSION: In this real-world study, while most patients received at least one biomarker test prior to 1L, <50% received all 5 tests. NGS testing also occurred in < 50% of patients but appeared to increase over time. The next phase of MYLUNG will evaluate contemporary ordering practices and turnaround times prospectively.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Antígeno B7-H1 , Biomarcadores , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Receptores Proteína Tirosina Quinases , Estudos RetrospectivosRESUMO
PURPOSE: The gemcitabine and oxaliplatin (GEMOX) has yielded among the longest progression-free survival durations in patients with advanced pancreatic cancer (APC). We postulated that adding bevacizumab would increase the effectiveness of GEMOX. METHODS: Eligible patients had stage III or IV pancreatic cancer, ECOG PS 0-2, and no prior gemcitabine. Treatment included 1,000 mg/m(2) intravenous gemcitabine over 100 min on day 1, 10 mg/kg intravenous bevacizumab on day 1, and 100 mg/m(2) oxaliplatin given on day 2. Cycles were repeated every 2 weeks. CT imaging was performed every 6 weeks. RESULTS: Fifty patients were enrolled: 14 had stage III disease, the remainder stage IV. Median age was 59 years. Fourty-five patients were ECOG 0-1. The grade 3-4 toxicity rate was 94%; fatigue (47%) and nausea (40%) were frequent. One patient died after a bowel perforation; a second died of a CVA. The median PFS was 4.9 months; median survival was 11.9 months; 1 year survival was 42%. Locally advanced patients lived 12.8 months; metastatic patients lived 10.2 months. Patients developing grade 3 hypertension were more likely to have a radiologic response (P = .012); survival among the top and bottom quintiles of hypertension was 14.7 and 6.2 months, respectively. Survival correlated with baseline CA 19-9 (P = .004) and radiologic response. The overall response rate was 36%; 34% demonstrated stable disease. CONCLUSIONS: The GEMOX/bevacizumab regimen demonstrated an excellent median overall survival but did not meet our objective of a 14 month median survival. Toxicity was significant. We do not recommend further evaluation of this regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , GencitabinaRESUMO
PURPOSE: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin dsFv-PE38) in patients with mesothelin-expressing cancers. EXPERIMENTAL DESIGN: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced mesothelioma (n = 20), ovarian (n = 12), and pancreatic (n = 2) cancer. RESULTS: The initial cohort of 17 patients received SS1P QOD x 6 doses and the MTD was 18 microg/kg/dose. Dose-limiting toxicities (DLT) included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation, 17 patients were treated on the QOD x 3 schedule and the MTD was 45 microg/kg/dose. The DLT was grade 3 pleuritis and was seen in two of two patients treated at a dose of 60 microg/kg and in one of nine patients treated at a dose of 45 microg/kg. At the MTD of 45 microg/kg, the mean C(max) of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable disease (including 2 with resolution of ascites), and 10 had progressive disease. CONCLUSIONS: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a group of heavily pretreated patients. Phase II clinical trials of SS1P are being planned for malignant mesothelioma and other mesothelin-expressing malignancies.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Imunotoxinas/administração & dosagem , Mesotelioma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: This study assesses the efficacy of epirubicin and docetaxel as neoadjuvant therapy for women with breast cancer. PATIENTS AND METHODS: This is a single institution, single arm, phase II study of epirubicin given at 75 mg/m(2) and docetaxel at 75 mg/m(2) every three weeks for four cycles prior to surgical excision in women with large breast cancers. Pegfilgrastim was routinely administered as primary prophylaxis against febrile neutropenia. RESULTS: Out of the 18 patients enrolled on the study, 12 (66.7%) had a clinical response and 13 (72.2%) had a pathologic response, with a pathologic complete response of 5.6%. Pre-menopausal women and patients with estrogen receptor positive tumors had a higher response rate. One patient died due to sepsis and febrile neutropenia. CONCLUSION: Combination chemotherapy with epirubicin and docetaxel is highly active against breast cancer. With close monitoring for toxicity, this combination can be safely administered with mild side-effects.