Patterns of pharmaceutical therapy in advanced melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20014-e20014 ◽  
Author(s):  
Aikaterini Bilitou ◽  
Zhongyun Zhao ◽  
Beth L. Barber ◽  
Genevieve Sian Clapton ◽  
Deborah Saltman

e20014 Background: Since 2011, two therapies that provide novel approaches to the treatment of advanced (unresectable or metastatic) melanoma have been introduced to the market: ipilimumab for second line and vemurafenib for BRAF mutation-positive melanoma. It is not known how the new drugs influence treatment; this study investigated current treatment patterns in advanced melanoma. Methods: A clinician-validated, web-based survey was administered between August and November 2012 to clinicians who treat advanced melanoma in France, Germany, Italy, Spain, and the UK. Respondents were asked about their treatment of patients in the previous 12 months, including treatment modalities and pharmaceutical therapies used, and factors that affect treatment choice. Results: 150 oncologists and dermatologists completed the survey, 30 in each country. Pharmaceutical therapy was more commonly used than other treatment modalities and varied by stage of disease. A high proportion of patients with late stage of disease were treated with pharmaceutical therapy in Germany (85% in M1B) and France (83% in M1C). Among the countries, 51% (Italy) to 87% (France) of respondents test BRAF mutation status. In patients with wild-type BRAF tumors, dacarbazine, which has not been shown to provide any overall survival benefit, was the most commonly used drug for first-line therapy in all countries. In mutated BRAF tumors, vemurafenib was the most commonly used drug in first line therapy in 3 of 5 countries. There was no standard of care in second line for either patients with wild-type or mutated-BRAFtumors; therapies used included fotemustine, temozolomide, interferon, paclitaxel, and ipilimumab. Conclusions: Treatment options for patients with advanced melanoma are limited, particularly for patients with wild-type BRAF disease. In second line, there does not appear to be an established standard of care: a range of treatments are used, including several not indicated for melanoma.

2021 ◽  
Vol 10 (21) ◽  
pp. 5166
Author(s):  
Chih-Chien Wu ◽  
Chao-Wen Hsu ◽  
Meng-Che Hsieh ◽  
Jui-Ho Wang ◽  
Min-Chi Chang ◽  
...  

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.


2010 ◽  
Vol 4 (5) ◽  
pp. 673-677
Author(s):  
Julian H. Elliott

Abstract Limited access to virological monitoring has led to a high prevalence of resistance to nucleoside reverse transcriptase inhibitors (NRTIs) at the time of first line failure in most studies from low- and middle-income countries (LMIC). Nevertheless, the current standard of care is to include NRTIs in second line regimens. The activity of tenofovir/emtricitabine following failure of stavudine/lamivudine or zidovudine/lamivudine is dependent on the sensitivity of the monitoring strategy used during first line therapy and the threshold for switching, whereas these factors are less important if the opposite sequencing strategy is used. Boosted protease inhibitors (PIs) are the foundation of effective second-line therapy with demonstrated efficacy in early salvage regimens and high barrier to resistance. Lopinavir/ritonavir and ritonavir-boosted atazanavir have recently been described by the World Health Organization as preferred boosted PIs for use in LMIC. Alternative approaches currently under investigation include boosted PI monotherapy, dual boosted PIs, and the combination of raltegravir (an HIV integrase inhibitor) and a boosted PI.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S680-S681
Author(s):  
Carly Heck ◽  
Judith Martin ◽  
Marcia Kurs-Lasky

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


2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll

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.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 324-324
Author(s):  
Ciro Celsa ◽  
Giuseppe Cabibbo ◽  
Marco Enea ◽  
Salvatore Battaglia ◽  
Giacomo Emanuele Maria Rizzo ◽  
...  

324 Background: Atezolizumab plus Bevacizumab represents the new best performing first-line approach for unresectable hepatocellular carcinoma (u-HCC). However, the best sequential strategy after every first-line failure (for progression or intolerance) remains elusive, and options for retreating patients failing Atezolizumab plus Bevacizumab with multi-kinase inhibitors (MKI) or immune checkpoint inhibitor (ICI) are yet undefined. Methods: We developed a Markov model to analyze simulated-Overall Survival (s-OS) of second-line ICIs or MKIs after first-line Atezolizumab plus Bevacizumab over a lifetime horizon. For first-line therapy, PFS of Atezolizumab plus Bevacizumab was extracted from Imbrave 150 trial and it was used as endpoint since it is not influenced by post-progression survival. For second-line retreatment, pooled OS of MKIs (Regorafenib and Cabozantinib), or ICIs (Nivolumab and Pembrolizumab) were adopted. Survival estimates for sequential settings considered the proportion of patients who did not receive second-line therapy due to death during first-line therapy. Individual patient survival data were extracted from PFS and OS Kaplan-Meier curves of RESORCE trial for Regorafenib, CELESTIAL trial for Cabozantinib, CheckMate-040 for Nivolumab and Keynote-240 for Pembrolizumab. Each reconstructed survival curve was inspected for accuracy and was compared with originally published curves. Results: First-line Atezolizumab plus Bevacizumab followed by second-line ICIs turned on from the model as the best sequential strategy (median s-OS 24 months; 95% Confidence Interval (CI) 23-26 months) and extends survival when compared Atezolizumab plus Bevacizumab followed by MKIs (median s-OS 20 months; 95% CI 19-21 months). Conclusions: To our knowledge and given the absence of adequately designed sequential RCTs, this is the first model to date which suggests, with a proper methodological approach, an accurate estimate of outcome of patients with u-HCC treated by sequential systemic therapies. In patients with u-HCC failing first-line treatment, modelling estimates of s-OS for each retreatment strategies may assist in choosing the most promising sequences in order to plan appropriate RCTs.


2018 ◽  
Vol 29 ◽  
pp. ix150 ◽  
Author(s):  
D. Planchard ◽  
M. Boyer ◽  
J.-S. Lee ◽  
A. Dechaphunkul ◽  
P. Cheema ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document