Economic evaluation of crizotinib, alectinib, ceritinib, and brigatininb in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) as second-line treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21104-e21104
Author(s):  
Nimer S. Alkhatib ◽  
Briana Choi ◽  
Hala Halawah ◽  
Matthias Calamia ◽  
Dexter Gulick ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Incremental Cost ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Reference Drug ◽  
First Line Therapy ◽  
Line Therapy ◽  
Life Years

e21104 Background: Crizotinib, alectinib, ceritinib, and brigatinib are approved as second line treatment for ALK+ NSCLC. Crizotinib was the first ALK inhibitor for first line therapy approved by Food and Drug Administration (2011) then ceritinib (2014), alectinib (2015), and brigatinib (2017) were approved as second line drugs. Following more data, these agents were approved as the first line therapy (2017 for ceritinib and alectinib; 2020 for brigatinib). These remain as a treatment option in patients who fail the first line therapy. Cost-effectiveness/utility analyses were conducted to assess clinical efficacy with varying costs of the agents. Methods: A three state Markov model were assumed (progression free, progression and death). Progression free survival (PFS) curves were digitized and fitted with exponential function. US payer perspective, a lifetime horizon, and discount rate of 3% were applied. Drug costs were Redbook wholesale acquisition cost. Other costs included were monitoring, adverse events and disease progression from published data (US$ 2020). Adverse events reported >5% in patients were included. Measured outcomes were PFS life years (PFSLY) and quality adjusted life years (PFSQALY). Crizotinib was the reference drug. Incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) and lost were estimated. Base case (BCA) and probabilistic sensitivity analyses (PSA) were conducted. Results: Crizotinib was the reference drug for the following outcomes. For alectinib, with the decremental cost of -$14,653 (-$14,712), the incremental PFSLY of 0.16 (0.16) and PFSQALY of 0.05 (0.05) resulted in an ICER / PFSLYG of -$89,337 (-$88,604) and an ICUR / PFSQALYG of -$269,835 (-$266,510). For brigatinib, with the decremental cost of -$14,975 (-$14,954), the incremental PFSLY of 0.01 (0.01) and PFSQALY of ̃0.01 (0.02) yielded an ICER / PFSLYG of -$1,982,962 (-$1,431,631) and an ICUR / PFSQALYG of -$2,140,534 (-$570,538). For ceritinib, with the incremental cost of $7,590 ($7,514), there were decremental PFSLY of -0.01 (-0.01) and PFSQALY of -0.03 (-0.03). Conclusions: As second line treatment, crizotinib, ceritinib, and brigatinib had comparable PFSLYs and PFSQALYs while alectinib had the most PFSLY and PFSQALY and the lowest cost. Therefore, alectinib is the most cost-effective treatment for treating ALK+ NSCLC as the second line therapy.[Table: see text]

Economic evaluation of crizotinib, alectinib, ceritinib, and brigatinib in treatment naïve anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21102-e21102
Author(s):  
Briana Choi ◽  
Nimer S. Alkhatib ◽  
Hala Halawah ◽  
Matthias Calamia ◽  
Dexter Gulick ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Incremental Cost ◽  
Base Case ◽  
First Line ◽  
Lifetime Horizon ◽  
Reference Drug ◽  
Anaplastic Lymphoma ◽  
Life Years ◽  
Cost Effective Treatment

e21102 Background: Crizotinib was approved by the FDA (2011) as the first ALK inhibitor for ALK+ NSCLC as the first line drug. This was followed by the approval as second line treatment of ceritinib (2014), alectinib (2015) and brigatinib (2017); and, following more data, now also as first line therapies in ALK+ NSCLC. With varying costs and clinical benefits for progression free survival (PFS), cost effectiveness/utility analyses were conducted. Methods: A 3 state Markov model was built including progression free, progression and death. PFS and overall survival curves were digitized and exponential functions were fit the curves for extrapolation beyond trial follow up. A lifetime horizon, US payer perspective, and a discount rate of 3% were applied. Drug costs were based on Redbook Wholesale Acquisition Cost while costs of adverse events, monitoring, disease progression were from literatures (US$ 2020). Adverse events reported at > 5% were included. Crizotinib was used as reference treatment. PFS life years (PFSLY), quality adjusted life years (PFSQALY), incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) were estimated in base case (BCA) and probabilistic sensitivity analyses (PSA). Results: Crizotinib was the reference drug in the following estimations. For alectinib, at incremental cost of $7,789 (PSA $7,719), the incremental PFSLY of 1.10 (1.10) and PFSQALY 1.07 (1.07) yielded an ICER of $7,109 ($7,030) / PFSLYG and an ICUR of $7,278 ($7.197) / PFSQALYG. For ceritinib, at incremental cost of $88,688 ($88,450), the incremental PFSLY of 1.02 (1.02) and PFSQALY of 1.01 (1.01) resulted in an ICER of $86,970 ($86,729) / PFSLYG and an ICUR of $87,472 / PFSQALYG. For brigatinib, at incremental cost of $84,680 ($83,986), the incremental PFSLY of 1.01 (1.01) and PFSQALY of 1.02 yielded an ICER of $83,774 ($83,073) / PFSLYG and an ICUR of $82,666 ($81,976) / PFSQALYG. Conclusions: Ceritinib had the highest lifetime cost and comparable PFSLY and PFSQALY to brigatinib. However, alectinib reported the highest PFSLY and PFSQALY gained while having lower costs than ceritinib and brigatinib, therefore being the most cost-effective treatment for naïve ALK+ NSCLC.[Table: see text]

The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL)

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2949-2951 ◽  
Author(s):  
Giovanni Palladini ◽  
Vittorio Perfetti ◽  
Stefano Perlini ◽  
Laura Obici ◽  
Francesca Lavatelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Primary Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Symptomatic Bradycardia ◽  
Intermediate Dose

AbstractBased on the efficacy of thalidomide in multiple myeloma and on its synergy with dexamethasone on myeloma plasma cells, we evaluated the combination of thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary amyloidosis (AL) whose disease was refractory to or had relapsed after first-line therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall, 15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5-8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic bradycardia was a common (26%) adverse reaction. The combination of thalidomide and dexamethasone is rapidly effective and may represent a valuable second-line treatment for AL.

scholarly journals Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 131
Author(s):  
Antonio Lopez-Beltran ◽  
Alessia Cimadamore ◽  
Ana Blanca ◽  
Francesco Massari ◽  
Nuno Vau ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Durable Response ◽  
First Line Therapy ◽  
Line Therapy

A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.

Choosing First-Line Therapy for Follicular Lymphoma (FL): A Decision Analysis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 670-670
Author(s):  
Rebecca L. Olin ◽  
Peter A. Kanetsky ◽  
Thomas Ten Have ◽  
Sunita Dwivedy Nasta ◽  
Stephen J. Schuster ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Decision Analysis ◽  
Prescribing Patterns ◽  
Low Grade ◽  
Second Line ◽  
First Line ◽  
Anthracycline Cardiotoxicity ◽  
First Line Therapy ◽  
Line Therapy ◽  
Life Years

Abstract Introduction: There is no standard of care for first-line therapy of low-grade FL. In US practice, the most common strategy is rituximab with combination chemotherapy. However, the optimal choice of regimen remains controversial; options include RCVP, RCHOP and R-Fludarabine-based chemotherapy (RFlu). Because data from randomized clinical trials are not available and unlikely to be generated in the future, we performed a decision analysis comparing RCVP, RCHOP, and RFlu as first-line therapy for FL. Methods: We constructed a Markov model of sequential first- and second-line therapy based on prescribing patterns in the US. The endpoint of the model was quality-adjusted time to tertiary referral for therapy such as RIT or autologous transplant (≥3rd line). A literature review was performed of the Medline database and international meeting abstracts. Clinical trials of both untreated and previously treated patients were systematically evaluated using explicit eligibility criteria. Data were extracted regarding response rates, treatment-related mortality, and progression-free survival (PFS). Weighted estimates were obtained using a fixed effects meta-analysis. The model also incorporated published data on heath state utilities, risk of anthracycline cardiotoxicity and fludarabine-related delayed cytopenias. Primary and sensitivity analyses were performed using TreeAge software. Results: The optimal treatment strategy consisted of RCHOP in first-line followed by RFlu in second-line (9.0 quality-adjusted life years; QALYs). Strategies containing RCVP in either first- or second-line were inferior (6.2–7.7 QALYs). The model was sensitive to first-line PFS of RCHOP and RFlu when these were varied over the range of estimates obtained from individual published trials. The model was robust in sensitivity analysis of most other parameters, including rate of delayed cytopenias after RFlu, anthracycline cardiotoxicity, and quality of life adjustments. Conclusions: Using decision analysis, the optimal first-line therapy for low-grade FL is RCHOP, followed by RFlu in second-line. This strategy maximizes quality-adjusted time to tertiary therapy. Use of RCVP does not improve overall quality-adjusted time relative to more intensive therapies.

Modified FOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab beyond first progression in advanced colorectal cancer: CCOG-0801 study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 641-641
Author(s):  
Kiyoshi Ishigure ◽  
Goro Nakayama ◽  
Keisuke Uehara ◽  
Hiroyuki Yokoyama ◽  
Akiharu Ishiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bleeding Event ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
To Receive

641 Background: Bevacizumab provides survival benefit as the first-line and second-line therapies in metastatic colorectal cancer (mCRC). A large observational study suggested use of bevacizumab beyond first progression (BBP) improved survival. This prompted us to conduct a multicenter phase II study of mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizimab in mCRC to further explore the strategy of BBP in Japanese patients. Methods: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. If the patient failed to receive the second-line treatment due to medical reasons or refusal, the PFS during the first-line therapy was used for analysis. Secondary endpoints were PFS, overall survival (OS), response rate (RR), disease control rate (DCR) and safety. Results: In the first-line therapy, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7%, DCR of 89.4% and median PFS of 11.7 months. Thirty patients went on to receive the second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6%, DCR of 62.1%, and median PFS of 6.0 months. Median 2nd PFS was 16.2 months. Median survival time did not reach the median follow-up time of 27.4 months. Severe adverse events associated with bevacizumab during the first-line therapy were a venous thromboembolic event in one case (2%), a grade 2 bleeding event in one case (2%) and GI perforation in one case (2%). However, no critical events associated with bevacizumab were reported during the second-line therapy. Conclusions: The planned continuation of bevacizumab during the second line treatment is feasible in Japanese mCRC patients. A prospective randomized control study to confirm the efficacy has to be conducted in the future.

scholarly journals Cost-Effectiveness of Lorlatinib as a First-Line Therapy for Untreated Advanced Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
SiNi Li ◽  
JianHe Li ◽  
LiuBao Peng ◽  
YaMin Li ◽  
XiaoMin Wan
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Anaplastic Lymphoma Kinase ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Anaplastic Lymphoma ◽  
First Line Therapy ◽  
Line Therapy ◽  
Life Years

IntroductionRecently, a phase III CROWN trial compared the efficacy of two anaplastic lymphoma kinase (ALK) inhibitors and demonstrated that lorlatinib displayed clinical improvement over crizotinib for advanced non-small cell lung cancer (NSCLC) patients. Therefore, the aim of this study was to estimate the cost-effectiveness of lorlatinib as a first-line therapy for patients with advanced ALK-positive (+) NSCLC.Materials and MethodsA cost-effectiveness analysis was performed using a microsimulation model from the US payer perspective and a lifetime horizon (30 years) in patients with previous untreated advanced ALK+ NSCLC. Based on the CROWN trial, patient characteristics were obtained, and the transition probabilities were estimated. All direct costs were derived from official sources and published literature. The main outcomes of the model were total costs, incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs), and life years (LYs). One-way and probabilistic sensitivity analyses and multiple scenario analyses were conducted to test the robustness of the model outcomes.ResultsIn the base case analysis, in which 1 million patients were simulated, treatment with lorlatinib or crizotinib as the first-line treatment was related to a mean cost of $909,758 and $616,230 (incremental cost: $293,528) and a mean survival of 4.81 QALYs and 4.09 QALYs (incremental QALY: 0.72) per patient, respectively. The main drivers of cost effectiveness were drug price and subsequent cost. PAS indicated that lorlatinib has 90% cost-effectiveness when compared to crizotinib when the willingness-to-pay (WTP) threshold in increased to $448,000/QALY. Scenario analysis demonstrated that lorlatinib has 100% cost-effectiveness at a WTP threshold of 200,000/QALY compared to crizotinib treatment when the price of lorlatinib is decreased to 75% ($424.5) of its original price.ConclusionsIn this study, lorlatinib was unlikely to be cost effective compared with crizotinib for patients with previously untreated advanced ALK+ NSCLC at a WTP threshold of 200,000/QALY.

scholarly journals COST-EFFECTIVENESS ANALYSIS OF AVELUMAB TREATMENT FOR PATIENTS WITH METASTATIC MERKEL CELL CARCINOMA

2020 ◽  
Vol 66 (2) ◽  
pp. 109-119
Author(s):  
Nikolay Avksentev ◽  
Lev Demidov ◽  
Maksim Frolov ◽  
Aleksandr Makarov
Keyword(s):  
Cost Effectiveness ◽  
Incremental Cost ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Neuroendocrine Differentiation ◽  
Skin Tumor ◽  
Line Treatment ◽  
Second Line ◽  
Merkel Cell ◽  
Life Years

Merkel cell carcinoma (MCC) is a rare primary malignant skin tumor with epithelial and neuroendocrine differentiation. According to the Russian clinical recommendations, MCC accounts for around 650 new cases per year in Russia. Avelumab is a human IgG1 monoclonal antibody that targets cancer cells through the inhibition of the immune checkpoint protein PD-L1 and can be used as a 2nd line treatment of metastatic MCC (mMCC). The aim of the study is to conduct a clinical and economic evaluation of avelumab as a second-line treatment in patients with mMCC from the perspective of Russian health care. Methods. Standard chemotherapy regimens were considered as a comparator for avelumab. We proposed a mathematical model of MCC progression and calculated direct medical costs during 6 years of treatment. Incremental cost-effectiveness ratios for avelumab (vs chemotherapy) were compared with the corresponding ratios for another PD-1 inhibitor included in Vital and Essential Drug List (VEDL). Results. Life-years gained (LYG) for avelumab were 2.21 years, compared to 0.39 LYG for chemotherapy. The average costs of using avelumab were 9 156 731 RUB per patient, compared to 60 743 RUB when using chemotherapy. Incremental cost-effectiveness ratio (ICER) for avelumab (vs chemotherapy) was 5 012 867.70 RUB per one LYG, which was 54.8% lower than ICER for pembrolizumab (vs docetaxel) as a second-line treatment in patients with non-small cell lung cancer. ICER for avelumab vs chemotherapy was 11,940,043.38 RUB per one progression-free LYG, which was 40.9% lower than ICER for pembrolizumab (vs chemotherapy) as a treatment in patients with ipilimumab-refractory advanced melanoma.

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