scholarly journals Antiangiogenic therapy in pretreated patients with lung adenocarcinoma without activating mutations: new features

2021 ◽  
Vol 23 (3) ◽  
pp. 425-427
Author(s):  
Elena V. Reutova ◽  
Konstantin K. Laktionov
Keyword(s):  
Lung Adenocarcinoma ◽  
Antiangiogenic Therapy ◽  
Angiogenesis Inhibitor ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Activating Mutations ◽  
Therapy Option ◽  
Pretreated Patients ◽  
Third Line

The possibilities of treatment of patients with metastatic non-small cell lung cancer have significantly expanded in the recent years. Several combined regimens of chemoimmunotherapy are currently being proposed as the first line, some patients with PD-L1 overexpression may be prescribed pembrolizumab or atezolizumab in monotherapy. Standard platinum-containing chemotherapy (PCT) has lost its position and is relevant only for contraindications to immuno-oncological (IO) drugs. The change in the standart of the first line inevitably led to the search for new optimal modes of the second line. The strategy of "angio-immunogenic switching" is promising after progression on the regimens with IO, anti-angiogenic drugs are used. Nintedanib a multikinase angiogenesis inhibitor in combination with docetaxel is a standard second-line therapy option in patients with lung adenocarcinoma after progression on PCT. The effectiveness of this regimen is being studied in a prospective non-interventional VARGADO study. The patients were divided into 3 cohorts, depending on which regimen was used earlier one line of PCT or PCT, followed by IO or chemoimmunotherapy. The results showed that the combination of docetaxel + nintedanib was effective both as a third line (after PCT and IO), and in the second after chemoimmunotherapy. The research is ongoing.

scholarly journals Effects of removing reimbursement restrictions on targeted therapy accessibility for non-small cell lung cancer treatment in Taiwan: an interrupted time series study

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e022293 ◽  
Author(s):  
Jason C Hsu ◽  
Chen-Fang Wei ◽  
Szu-Chun Yang
Keyword(s):  
Lung Cancer ◽  
Targeted Therapies ◽  
Interrupted Time Series ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

InterventionsTargeted therapies have been proven to provide clinical benefits to patients with metastatic non-small cell lung cancer (NSCLC). Gefitinib was initially approved and reimbursed as a third-line therapy for patients with advanced NSCLC by the Taiwan National Health Insurance (NHI) in 2004; subsequently it became a second-line therapy (in 2007) and further a first-line therapy (in 2011) for patients with epidermal growth factor receptor mutation-positive advanced NSCLC. Another targeted therapy, erlotinib, was initially approved as a third-line therapy in 2007, and it became a second-line therapy in 2008.ObjectivesThis study is aimed towards an exploration of the impacts of the Taiwan NHI reimbursement policies (removing reimbursement restrictions) related to accessibility of targeted therapies.SettingWe retrieved 2004–2013 claims data for all patients with lung cancer diagnoses from the NHI Research Database.Design and outcome measuresUsing an interrupted time series design and segmented regression, we estimated changes in the monthly prescribing rate by patient number and market shares by cost following each modification of the reimbursement policy for gefitinib and erlotinib for NSCLC treatment.ResultsTotally 92 220 patients with NSCLC were identified. The prescribing rate of the targeted therapies increased by 15.58%, decreased by 10.98% and increased by 6.31% following the introduction of gefitinib as a second-line treatment in 2007, erlotinib as a second-line treatment in 2008 and gefitinib as as first line treatment in 2011, respectively. The average time to prescription reduced by 65.84% and 41.59% following coverage of erlotinib by insurance and gefitinib/erlotinib as second-line treatments in 2007–2008 and following gefitinib as the first-line treatment in 2011.ConclusionsThe changes in reimbursement policies had a significant impact on the accessibility of targeted therapies for NSCLC treatment. Removing reimbursement restrictions can significantly increase the level and the speed of drug accessibility.

Bendamustine and Rituximab for the Treatment of Chronic Lymphocytic Leukemia: The Moffitt Cancer Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4620-4620
Author(s):  
Heather Barnes Pound ◽  
Viet Q. Ho ◽  
Celeste M. Bello ◽  
Jennifer L. Cultrera ◽  
Martine Extermann ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Response Rates ◽  
Primary Objective ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line

Abstract Abstract 4620 Introduction: Although bendamustine is approved for the treatment of chronic lymphocytic leukemia (CLL), the combination of bendamustine and rituximab (BR) is currently under active investigation in the relapsed/refractory setting as well as for front-line use. Emerging data now suggests BR is acceptable for first-line use and indeed is listed in the NCCN Compendia as a first-line option. Herein, we report the results of a single-center retrospective review of BR use in first-, second- and third-line and beyond and its effects on response rate. Methods: We retrospectively reviewed 21 consecutive patients with CLL that received BR at the Moffitt Cancer Center (MCC) between July 2008 and November 2010. Bendamustine was dosed at 70 mg/m2 IV on Days 1 and 2 every 3–4 weeks; rituximab was dosed at 375 mg/m2 IV once with each cycle along with anti-microbial prophylaxis. Data collected included, but was not limited to age, gender, cytogenetic profile, number of previous therapies, Rai stage at time of treatment and response (based on 1996 NCI-WG definition). The primary objective was to assess response rates. The major secondary objective was to assess the effect of cytogenetics on response rates. All analyses were performed using descriptive statistics. Results: Twenty-one patients received treatment with BR; 7 patients received BR as first-line therapy, 7 received BR as second line therapy and the remaining 7 received BR as third-line therapy or beyond. The median age at time of treatment was 66; 12 of 21 patients were male (57%); All Rai Stages were represented, Stage 0 (n=1), Stage 1 (n=4), Stage 2 (n= 3), Stage 3 (n=5), Stage 4 (n=6). 38% of patients were positive for Del11q, 33% for Del13q, 9.5% for Del17p, and 9.5% for mutated IgVH. In previously untreated patients, 6/7 had a documented complete remission (CR) (71.4%) or partial (PR) (14.3%) response; one patient progressed (PD) on therapy. In second-line therapy, all patients had a documented CR (28.6%) or PR (71.4%). In patients treated with BR as 3rd or 4th line therapy, 3 patients had a CR, 2 patients had stable disease (SD), and 2 had PD. Of the 8 patients with Del11q, 37.5% achieved a CR, 4 had PR and 1 had PD. Of the 7 patients with Del13q, 4 achieved CR and 3 had a PR. Both patients with Del17p had PD. Of the 2 patients with mutated IgVH, one patient achieved a PR while the other had PD. Conclusion: Based on these results, the combination of bendamustine and rituximab in patients with CLL is efficacious and well tolerated in patients with both newly diagnosed and relapsed/refractory disease. Disclosures: Off Label Use: Bendamustine and rituximab for CLL. Ho:Genentech: Honoraria; Cephalon: Consultancy. Cultrera:Genentech: Speakers Bureau. Sotomayor:Genentech: Membership on an entity’s Board of Directors or advisory committees. Pinilla-Ibarz:Genentech: Speakers Bureau; Cephalon: Speakers Bureau.

K-RAS codon 13 mutation in advanced colorectal cancer: A single-center retrospective study investigating prognostic outcomes and treatment strategies.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 633-633
Author(s):  
Vincenzo Dadduzio ◽  
Michele Basso ◽  
Maria Bensi ◽  
Silvia Cona ◽  
Eleonora Cerchiaro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Response To Therapy ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

633 Background: Ras genes are markers of resistance to anti-EGFR therapies. Emerging evidences suggest that each mutation, independently from its predictive role of response/resistance to specific treatments, may be expression of different diseases with different biologic behaviours. We collected data of mCRC patients harbouring K-Ras codon 13 mutation to evaluate response to therapy, PFS and OS. Methods: We retrospectively collected data of advanced colorectal cancer patients harbouring K-Ras codon 13 mutation treated at our Institution between 2004 and 2014. Results: A total of n.33 K-Ras codon 13 mutated patients were analysed. N.24 patients (72,7%) had synchronous metastatic disease. None of the patients received anti-EGFR treatment, while n.25 patients received anti-VEGF agent bevacizumab in association to chemotherapy with fluoropirimidines plus oxaliplatin and/or irinotecan (n.21 as frontline therapy, n.4 in second line). ORR was 51,5% (17/33) on first-line therapy, 22,2% (6/27) on second-line therapy and 16,6% (2/12) on third-line therapy. Median PFS was 14,1 months after first-line therapy, 9,3 months after second-line therapy, 6,4 months after third-line therapy. Median OS was 35,5 months (events: 19/33). N.14 patients received metastases surgery with radical intent. OS in this population has not been reached yet at a median follow-up of 38 months, even though all patients had a relapse. OS among patients undergone to systemic only strategy was 31 months. Conclusions: At our knowledge, this is the first report suggesting a favourable prognosis for K-ras codon 13 mutated patients, with a median overall survival even superior to pan-RAS wild-type patients. Indeed, the high percentage of advanced patients at diagnosis (72.7%), the high responsiveness to chemotherapy even in third line, the high percentage of patients converted to surgery (42.4%) in an unselected population, together with the high risk or relapse after surgery, suggest K-ras codon 13 mutated disease is probably a biologically aggressive disease. Nevertheless our data prompt that these patients may benefit aggressive strategies of treatment and multidisciplinary evaluation.

NET-02: A multi-center, randomised, phase II trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients (pts) with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma (PD-EP-NEC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4158-TPS4158
Author(s):  
Mairead Geraldine McNamara ◽  
Jayne Swain ◽  
Zoe Craig ◽  
Jonathan Wadsley ◽  
Nicholas Reed ◽  
...  
Keyword(s):  
Phase Ii Trial ◽  
Phase Iii ◽  
High Grade ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Phase Iii Trial ◽  
Line Therapy ◽  
Platinum Based Chemotherapy ◽  
Therapy Option

TPS4158 Background: The prognosis for pts with PD-EP-NEC is poor. First-line treatment for advanced disease is etoposide/platinum-based chemotherapy, analogous to that of high grade lung NEC, with no standard second-line treatment, and is an area of unmet need. Methods: This is a multi-centre, randomised, phase II trial of nal-IRI; 80mg/m2 intravenously (IV) over 90 mins, prior to 5-FU; 2400 mg/m2 infusion over 46 hrs and folinic acid, Q14 days, or docetaxel; 75mg/m2 IV over 60 mins, Q21 days, as second-line therapy in pts with progressive PD-EP-NEC (Ki-67 > 20%), with the overall aim of selecting a treatment for continuation to a phase III trial. The standard arm is that used in high-grade lung NEC, of which docetaxel is a second-line therapy option (NCCN guidelines) and combination regimens such as Irinotecan/5-FU are a second-line therapy option currently used without trial evidence for this subset of pts. Pts must have had prior treatment with first-line platinum-based chemotherapy, have documented disease progression and have an ECOG performance status of ≤2. This study plans to recruit 102 pts from 16 UK centres (over 37 mths). Primary endpoint is 6-mth progression-free survival (PFS) rate; trial is designed to have an 80% chance of demonstrating that the one-sided 95% confidence interval of the 6 mth PFS rate excludes 15%, if the true rate is at least 30%, where 30% is the required level of efficacy, and a rate of < 15% would give grounds for rejection. If both treatment arms exceed the required level of efficacy to warrant further evaluation in a phase III trial, treatment with the higher PFS rate at 6 mths will be selected. Secondary endpoints include overall survival, objective response rate, toxicity, quality of life, serum neuron-specific enolase. Exploratory endpoints include quantification of circulating tumour cells (CTCs), circulating tumour deoxyribonucleic acid (ctDNA) and molecular profiling of CTCs, ctDNA and tumour tissue, and generation of CTC-derived xenografts. This trial is open and has enrolled 6 pts at time of submission. Clinical trial information: 10996604.

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li
Keyword(s):  
Colorectal Cancer ◽  
Adverse Event ◽  
Metastatic Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Clinical Prognosis ◽  
Line Therapy ◽  
Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

scholarly journals 1338. Analysis of Prescription Guideline Adherence in Pediatric Outpatient Pneumonia Treatment

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S680-S681
Author(s):  
Carly Heck ◽  
Judith Martin ◽  
Marcia Kurs-Lasky
Keyword(s):  
Drug Allergy ◽  
Health Concern ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Comparison Results ◽  
Significant Difference ◽  
Recommended Therapy

Abstract Background Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy. Methods Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded. Results Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction. Demographics Comparison Results Justification for Second-line / Other Therapy and Drug Allergy Results Conclusion This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP. Disclosures All Authors: No reported disclosures

Phase II Study of Docetaxel and Gefitinib as Second-Line Therapy in Gemcitabine Pretreated Patients with Advanced Pancreatic Cancer

Oncology ◽  
2009 ◽  
Vol 76 (4) ◽  
pp. 270-274 ◽  
Author(s):  
Joanna M. Brell ◽  
Khalid Matin ◽  
Terry Evans ◽  
Robert L. Volkin ◽  
Gauri J. Kiefer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Pancreatic Cancer ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Pretreated Patients

Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

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