scholarly journals HIV-1 Drug Resistance and Third-Line Therapy Outcomes in Patients Failing Second-Line Therapy in Zimbabwe

2018 ◽  
Vol 5 (2) ◽  
Author(s):  
Cleophas Chimbetete ◽  
David Katzenstein ◽  
Tinei Shamu ◽  
Adrian Spoerri ◽  
Janne Estill ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Line Treatment ◽  
Second Line ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Cd4 Cell Count ◽  
Line Therapy ◽  
Third Line ◽  
Cd4 Cell ◽  
Third Line Treatment

Abstract Objectives To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe. Methods Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program. Risk factors for major PI resistance were assessed by logistic regression. Third-line treatment was provided as Darunavir/r, Raltegravir, or Dolutegravir and Zidovudine, Abacavir Lamivudine, or Tenofovir. Results Genotypes were performed on 86 patients who had good adherence to treatment. The median duration of first- and second-line ART was 3.8 years (interquartile range [IQR], 2.3–5.1) and 2.6 years (IQR, 1.6–4.9), respectively. The median HIV viral load and CD4 cell count were 65 210 copies/mL (IQR, 8728–208 920 copies/mL) and 201 cells/mm3 (IQR, 49–333 cells/mm3). Major PI resistance-associated mutations (RAMs) were demonstrated in 44 (51%) non-nucleoside reverse transcriptase inhibitor RAMs in 72 patients (83%) and nucleoside reverse transcriptase inhibitors RAMs in 62 patients (72%). PI resistance was associated with age >24 years (P = .003) and CD4 cell count <200 cells/mm3 (P = .007). In multivariable analysis, only age >24 years was significantly associated (adjusted odds ratio, 4.75; 95% confidence interval, 1.69–13.38; P = .003) with major PI mutations. Third-line DRV/r- and InSTI-based therapy achieved virologic suppression in 29/36 patients (81%) after 6 months. Conclusions The prevelance of PI mutations was high. Adolescents and young adults had a lower risk of acquiring major PI resistance mutations, possibly due to poor adherence to ART. Third-line treatment with a regimen of Darunavir/r, Raltegravir/Dolutegravir, and optimized nucleoside reverse transcriptase inhibitors was effective.

Safety and Efficacy of Bortezomib and Dexamethasone (BD) in Multiple Myeloma as First-Line, Second-Line or Third-Line Treatment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4817-4817
Author(s):  
Juan Li ◽  
Beihui Huang ◽  
Ying Zhao ◽  
Dong Zheng ◽  
Shaokai Luo
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Median Time ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Third Line ◽  
Third Line Treatment

Abstract Purpose: To compare efficacy and safety of BDbortezomib and dexamethasone in multiple myeloma as first-line, second-line or third-line treatment. Patients and methods: 18 patients(pts) treated with BD (bortezomig 1.3mg/m2 on d 1,4,8,11 and dexamethasone 20mg on d 1–4 in a 21-day cycle). Responses were evaluated by the criteria of EBMT but a nCR was included. Adverse events were graded by the WHO criteria. Results: The median age was 52.5 years, and 13 (72.2%) were male. Ig subtypes were IgG, (8 pts, 44.4%), IgA (4 pts, 22.2%), light chain (2 pts, 11.1%), and IgD (1 pts, 5.9%). Durine/Salmon staging: IIA 5.9% (1/18), IIB 5.9% (1/18), IIIA 72.2% (13/18), IIIB16.6% (3/18). BD was administered in first-line (4 pts, 22.2%), second-line (7 pts 38.9%) and third-line (7 pts, 38.9%). The median number of BD cycles was 2.5 (range, 1–6 cycles). 17 pts could be evaluated, overall response was 88.3%, including CR in 2 pts (11.7%), nCR in 5 pts (29.4%), PR in 7 pts (41.2%), MR in 1 pts(5.9%), NC in 1 pts(5.9%), PD in 1 pts(5.9%). Pts in the first-line group received a response of 100%(4/4), including nCR in 1 pts (25.0%), PR in 2 pts (50.0%), MR in 1 pts(25.0%). The second-line group received a response of 100%(7/7), including CR in 1 pts(14.3%), nCR in 3 pts (42.9%), PR in 3 pts (42.9%). Those received BD as third-line or more got a response of 66.7% (4/6), including CR in 1 pts(16.7%), nCR in 1 pts (16.7%), PR in 2 pts (33.3%). Aderse events included diarrhea 44.4% (8/18; grade IV: 2/18), thrombocytopenia 44.4% (8/18; grade III–IV: 7/18), fatigue 44.4% (8/18; grade IV: 1/18), peripheral neuropathy 33.3% (6/18, grade II:1/18), pyrexia 22.2%, infection 16.7% (3/18), headache 11.1%(2/18), parageusis 11.1%(2/18), hypotension 5.9%(1/18), hypoglycemia 5.9%(1/18) while combining with glipizide. The median time to minimum counts of platets was 14 days. The median time to most serious peripheral neuropathy appeared after treatment of 3 cycles. In 1 pts the therapy was disrupted by toxicity. Conclusion: BD demonstrated better response as first-line or second-line therapy than as third or more line therapy. Toxicities were torelated and manegable. There were no treatment related deaths.

scholarly journals Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV

2020 ◽  
Vol 14 ◽  
pp. 117955492095135 ◽  
Author(s):  
Wolfgang M Brueckl ◽  
Martin Reck ◽  
Achim Rittmeyer ◽  
Jens Kollmeier ◽  
Claas Wesseler ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Synergistic Effects ◽  
Stage Iv ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Third Line Treatment

Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV. Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred. Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first–line treatment.

scholarly journals Cost Effectiveness Analysis of Eribulin Mesylate as a Treatment for Metastatic Breast Cancer in Spain: Management in the Later Line of Therapy

10.36469/9834 ◽  
2015 ◽  
Vol 3 (2) ◽  
pp. 180-193
Author(s):  
Gabriel Tremblay ◽  
Unnati Majethia ◽  
Ilias Kontoudis ◽  
Jesús De Rosendo
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cost Effectiveness ◽  
Metastatic Breast ◽  
Sensitivity Analyses ◽  
Line Treatment ◽  
Second Line ◽  
Life Years ◽  
Third Line ◽  
Third Line Treatment

Background: Two thirds (62%) of metastatic breast cancer (MBC) patients in Western Europe have human epidermal growth factor receptor 2 (HER2)-negative disease, for which anthracyclines and taxanes are recommended as first-line treatments, followed by microtubule-targeting agents such as capecitabine, vinorelbine and/or eribulin. The study objective was to compare the cost-effectiveness of eribulin in Spain as a second-line treatment for HER2-negative MBC with its current status as a third-line treatment for patients who have received capecitabine. Methods: A Markov model was developed from the perspective of the Spanish healthcare system. The model had three health states: Stable; Progression and Death. In Stable, patients received eribulin or: capecitabine and vinorelbine for HER2-negative patients; primary treatment of physician’s choice (TPC) for post-capecitabine patients. In Progression, all patients received secondary TPC. Model inputs were overall survival, progression-free survival and costs relating to chemotherapies, grade 3/4 adverse events and healthcare utilization. Sensitivity analyses were conducted to identify uncertainty. Results: As second-line treatment, Eribulin was associated with a greater incremental benefit in life years (LYs) and quality-adjusted life years (QALYs) than capecitabine and vinorelbine. Erubilin as third-line treatment was associated with greater benefit in life years (LYs) and QALYs than TPC. The incremental cost-effectiveness ratios (ICERs) for eribulin were higher in the second-line than the third-line setting in terms of LYs (€35,149 versus €24,884) and QALYs (€37,152 versus €35,484). In both settings, deterministic sensitivity analyses demonstrated that the ICER is most sensitive to the eribulin price. Conclusion: Eribulin is cost-effective as second-line treatment for HER2-negative MBC patients in Spain; albeit, slightly less so than as third-line treatment for MBC patients who have received capecitabine (an ICER per QALY difference of €1,668). This difference may fall within the margin of error for the model and could potentially be addressed by a minor reduction in the eribulin price.

scholarly journals P469 Stay in class or switch out of class after anti-TNF failure in inflammatory bowel disease (IBD). Real-world data from a large district general hospital

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S414-S414
Author(s):  
H Johnson ◽  
S Vythilingam ◽  
S McLaughlin
Keyword(s):  
Clinical Remission ◽  
Disease Type ◽  
Line Treatment ◽  
Second Line ◽  
Real World Data ◽  
Effective Treatment Option ◽  
Significant Cost ◽  
Third Line ◽  
Biologic Drug ◽  
Third Line Treatment

Abstract Background Biosimilar infliximab (IFX) and adalimumab (ADA) are well-proven cost-effective anti-TNF drugs in IBD; in our practice, the majority of patients with IBD receive IFX or ADA first line. Since the introduction of Vedolizumab (VED) and Ustekinumab (UST) some have recommended switching out of class after failing a single anti-TNF. This practice has significant cost implications. To establish the outcome of treatment response in patients treated with a second anti-TNF agent after anti-TNF failure compared with the outcome of patients treated with VED and UST after anti-TNF failure. Methods We maintain a prospective IBD database. We searched our database for the outcomes of patients who failed their first anti-TNF drug but were in a clinical remission 6 months after changing to a second or third biologic drug. Disease type, age, gender and response to their second and third biologic drug were recorded. Clinical remission was defined as off steroids with calprotectin <250 and no symptoms of active IBD. Results Two hundred and eighty-seven patients were identified. One hundred and forty (48.8%) were male. Mean age was 43.2 (range 18–94). Disease type was 75 (26%) UC, 210 (73.2%) CD, 2 (0.7%) IBD-U. One hundred and ninety-three patients received IFX 1st line, 118 (40%) failed. Of these 84 (72%) received ADA, 28 (24%) VED and 6 (5%) UST second line. Remission with second-line treatment was achieved in 58 (69%); ADA, 18 (64%); VED, 6 (100%); UST. Remission with third line treatment; was achieved in 6 (100%); VED; 5 (100%); UST. Ninety-four patients received ADA 1st line, 33 (35%) failed. Of these 11 (33%) received IFX, 10 (30%) VED and 8 (24%) UST second line. Remission with second-line treatment was achieved in 6 (55%); IFX, 10 (100%); VED and 8 (100%); UST. Remission with third line treatment; was achieved in 1 (100%); VED, 4 (100%); UST. Conclusion Our data suggest that treatment with ADA after IFX failure is an effective treatment option whereas IFX treatment after ADA failure is less effective. It is interesting that the majority of those who failed the anti-integrin treatment second line responded to third line ADA. These data are consistent with earlier anti-TNF studies including GAIN (Gauging Adalimumab efficacy in Infliximab Non-responders) and SWITCH (Switch to adalimumab in patients with Crohn’s disease controlled by maintenance infliximab: prospective randomised SWITCH trial) which demonstrated that anti-TNF failure is not a class effect. We recommend prescribing a second anti-TNF after anti-TNF failure in preference to using an anti-integrin second line. This practice will lead to significant cost savings for the health care economy.

scholarly journals Late-line treatment in metastatic gastric cancer: today and tomorrow

2019 ◽  
Vol 11 ◽  
pp. 175883591986752 ◽  
Author(s):  
Elizabeth C. Smyth ◽  
Markus Moehler
Keyword(s):  
Gastric Cancer ◽  
Asian Population ◽  
Phase Iii ◽  
Response To Treatment ◽  
Evidence Based ◽  
Line Treatment ◽  
Second Line ◽  
Specific Patient ◽  
Line Therapy ◽  
Third Line

Survival for patients with unresectable advanced or recurrent gastric cancer (GC) remains poor and the historical lack of evidence-based therapeutic options after second-line therapy is reflected in current clinical guidelines for this condition. Despite uncertainty about optimal therapeutic strategies, further treatment is appropriate for some patients after failure of second line and may prolong survival. This approach has been reported in clinical trials and is becoming more common in real-world clinical settings. Several prognostic factors may increase the likelihood that a patient will be eligible for treatment in the third-line setting, including geographic location, status at diagnosis and response to treatment. There has been little progress over the last decade until the results from two large phase III randomized controlled trials completed in the last year: the ATTRACTION-2 trial with the programmed cell death-1 (PD-1) inhibitor, nivolumab, in an Asian population; and the TAGS trial with the oral chemotherapy trifluridine/tipiracil in a global population. Both ATTRACTION-2 and TAGS reported positive results in third-line treatment in advanced GC in specific patient groups. A further recently reported study, KEYNOTE-059, which was a single-arm phase II trial of the PD-1 inhibitor pembrolizumab in a mainly non-Asian population, has provided evidence supporting the use of this immunotherapy in patients with advanced GC. As further third-line options become available, more GC patients are expected to benefit from an individualized evidence-based approach to later-line therapy, with a common goal of extending survival and improving outcomes for their refractory disease.

Activity of new agents (NAs) as third-line treatment in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) showing a primary resistance (PRes) to NAs-based second line therapy after docetaxel (DOC): Preliminary results from a multicenter Italian study.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 216-216
Author(s):  
Orazio Caffo ◽  
Ugo De Giorgi ◽  
Gaetano Facchini ◽  
Lucia Fratino ◽  
Donatello Gasparro ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Objective Response ◽  
Progression Free Survival ◽  
Consecutive Series ◽  
Line Treatment ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Primary Resistance ◽  
Third Line ◽  
Third Line Treatment

216 Background: The androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, abiraterone acetate (AA), cabazitaxel (CAB), and enzalutamide (ENZ). It is postulated that some mechanisms of resistance may be common to all NAs. This may be crucial in planning their sequential use, mainly when a PRes to one of them is observed. The present study assessed the activity of NAs in pts who previously experienced a PRes to another NA administered after DOC. Methods: We collected data of pts who received sequentially two NAs after DOC in 32 Italian hospital. For each pt we recorded the clinical outcomes of all treatments received after DOC. For the study purpose, we consider with PRes all pts progressing within 3 months after second line NA start. All other pts were considered as without PRes. Results: A consecutive series of 271 mCRPC pts, median age 71 yrs (46-91), with bone (89%), nodal (56%) or visceral (19%) mets, was collected. All pts received NAs as second line after DOC (AA 54% – CAB 34%– ENZ 12%) and 54 (20%) showed a PRes. Among these, third line treatment [AA (31%), CAB (42%), and ENZ (27%)], produced a biochemical and an objective response rate of 11% in both cases, with a median progression free survival (PFS) and a median overall survival (OS) of 4 mos and 8 mos, respectively. No statistically significant differences were observed in terms of clinical outcomes on the basis of NA sequences (see Table). Conclusions: It appears from this preliminary data, that the activity of NAs in pts showing a PRes to second line NAs is very limited, regardless the NA is administered. [Table: see text]

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