Cost-effectiveness of front-line trials in metastatic colorectal cancer: Integrating the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) with the costs of drugs.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6622-6622
Author(s):  
Andrea Bonetti ◽  
Jcopo Giuliani

6622 Background: In Western Countries, colorectal cancer (CRC) is the second most common cause of death from cancer. In light of the relevant expenses of drugs it might be interesting to make a balance between the cost of the drugs and clinical parameters of interest such as progression free survival (PFS). Methods: Phase III randomized clinical trials (RCTs) that compared at least two front-line chemotherapy regimens for mCRC patients were evaluated. Differences in PFS between the different arms were calculated and compared with the pharmacological costs (at the Pharmacy of our Hospital) needed to get one month of PFS. Subsequently we applied the ESMO-MCBS (a 1 to 5 scale) to the above phase III RCTs. Results: Overall 28 phase III RCTs, including 19 958 patients, were analyzed. The FOLFOX resulted the least expensive (56 € per month of PFS gained) while the addition of irinotecan to FOLFOX (FOLFOXIRI) increased only marginally the costs (90 € per month of PFS gained). Treatments including the monoclonal antibodies showed a cost per month of PFS gained of 2823 € (FOLFIRI with cetuximab in KRAS wild-type patients and liver-only metastases), of € 15 822 (FOLFOX with panitumumab in KRAS wild type) and of 13 383 € (FOLFOX with bevacizumab). According to the ESMO-MCBS the treatments including an EGFR-inhibitor (cetuximab or panitunumab) were associated with a score of 4 while the inclusion of bevacizumab reached a score of 3. The remaining phase III RCTs obtained a low (grade 1-2) score.Dividing the costs per month of PFS gained with the grade of ESMO-MCBS, for each RCTs, we obtained the costs of each point of ESMO-MCBS per month of PFS gained. FOLFOX was confirmed as being the least expensive (18.7 €) while among treatments including a targeted biological agent panitunumab in combination with FOLFOX in K-RAS wild type patients was less expensive (3955 €) than the combinations FOLFOX-bevacizumab (13 383 €) and FOLFIRI-cetuximab in K-RAS wild type patients (21 854.6 €). Conclusions: Our data demonstrate a huge difference in cost per month of PFS gained and per each point of the ESMO-MCBS in modern front line treatments in mCRC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16032-e16032
Author(s):  
Ammari Abdelaziz ◽  
Linda Djebnoune ◽  
Besma Khater ◽  
Aicha Benmansour ◽  
Assia Bensalem

e16032 Background: The results of the different studies showed that the use of anti-EGFRs (Epidermal Growth Factor Receptor) in the management of mCRCs, confront the healthcare team to a new toxicity which until then, were unknown before the era of anti EGFRs. knowing that there were no Algerian patients in these studies, reason for us to do this work. Methods: Between October 2015 and October 2018, our work consists of an epidemiological, observational, descriptive, longitudinal prospective study, including all patients with metastatic colorectal cancer RAS wild type, receiving specific medical treatment with anti EGFR (Panitumumab or Cetuximab) from Medical Oncology Department of Didouche Mourad Hospital of Constantine and the Medical Oncology Department of Batna’s Anti Cancer Center, performance status 0-2, and age 18-75 years. We have completed this work whose main objective is to evaluate the toxicity of anti EGFRs in patients with mCRC RAS wild-type from the east of Algeria. Results: 60 patients received an anti EGFR (Panitumumab or Cetuximab), in our study the most common toxicity was folliculitis with an average onset time of 3.36 weeks and a frequency of 83% of grade 2 and 3. Xerosis was observed in 71% of patients. Paronychia was observed in 50% of patients, in addition to the classical toxicities observed with the different chemotherapy regimens used in mCRCs. For secondary objectives, the median progression free survival in our study was 12 months, with a 95% confidence interval [10,787-13,213]. This median progression-free survival is comparable to those reported in the major anti-EGFR trials. Conclusions: Our results suggest that the Algerian patients with metastatic colorectal cancer RAS wild-type have the same profile of toxicity comparing to the results from different international trials studying anti EGFRs.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii32-iii32
Author(s):  
H Noor ◽  
R Rapkins ◽  
K McDonald

Abstract BACKGROUND Tumour Protein 53 (TP53) is a tumour suppressor gene that is mutated in at least 50% of human malignancies. The prevalence of TP53 mutation is much higher in astrocytomas with reports of up to 75% TP53 mutant cases. Rare cases of TP53 mutation also exist in oligodendroglial tumours (10–13%). P53 pathway is therefore an important factor in low-grade glioma tumorigenesis. Although the prognostic impact of TP53 mutations has been studied previously, no concrete concordance were reached between the studies. In this study, we investigated the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. MATERIAL AND METHODS A cohort of 65 matched primary and recurrent fresh frozen tumours were sequenced to identify hotspot exons of TP53 mutation. Exons 1 to 10 were sequenced and pathogenic mutations were mostly predominant between Exons 4 and 8. The cohort was further expanded with 78 low grade glioma fresh frozen tissues and hotspot exons were sequenced. Selecting only the primary tumour from 65 matched tumours, a total of 50 Astrocytoma cases and 51 oligodendroglioma cases were analysed for prognostic effects of TP53. Only pathogenic TP53 mutations confirmed through COSMIC and NCBI databases were included in the over survival and progression-free survival analysis. RESULTS 62% (31/50) of astrocytomas and 16% (8/51) of oligodendrogliomas harboured pathogenic TP53 mutations. Pathogenic hotspot mutations in codon 273 (c.817 C>T and c.818 G>A) was prevalent in astrocytoma with 58% (18/31) of tumours with these mutations. TP53 mutation status was maintained between primary and recurrent tumours in 93% of cases. In astrocytoma, overall survival of TP53 mutant patients was longer compared to TP53 wild-type patients (p<0.01) but was not significant after adjusting for age, gender, grade and IDH1 mutation status. In contrast, astrocytoma patients with specific TP53 mutation in codon 273 showed significantly better survival compared to other TP53 mutant and TP53 wild-type patients combined (p<0.01) in our multivariate analysis. Time to first recurrence (progression-free survival) of TP53 mutant patients was significantly longer than TP53 wild-type patients (p<0.01) after adjustments were made, while TP53 mutation in codon 273 was not prognostic for progression-free survival. In oligodendroglioma patients, TP53 mutations did not significantly affect overall survival and progression-free survival. CONCLUSION In agreement with others, TP53 mutation is more prevalent in Astrocytoma and mutations in codon 273 are significantly associated with longer survival.


2016 ◽  
Vol 12 (7) ◽  
pp. e775-e783 ◽  
Author(s):  
Nicole P. Chappell ◽  
Caela R. Miller ◽  
Aaron D. Fielden ◽  
Jason C. Barnett

Purpose: Although the Food and Drug Administration has approved incorporation of bevacizumab (BEV) into the treatment of platinum-resistant ovarian cancer (PROC), cost-value measures are an essential consideration, as evidenced by the recent ASCO Value Framework initiative. We assessed the cost-effectiveness and reviewed the net health benefit (NHB) of this expensive treatment. Methods: A cost-effectiveness decision model was constructed using results from a phase III trial comparing BEV plus cytotoxic chemotherapy with chemotherapy alone in patients with PROC. The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA) trial demonstrated improvement in progression-free survival and quality of life in patients receiving BEV. Costs, paracentesis rates, and adverse events were incorporated, including subgroup analysis of different partner chemotherapy agents. Results: Inclusion of BEV in the treatment of platinum-resistant recurrent ovarian cancer meets the common willingness-to-pay incremental cost-effectiveness ratio (ICER) threshold of $100,000 per progression-free life-year saved (LYS) for 15-mg/kg dosing and approaches this threshold for 10-mg/kg dosing, with an ICER of $160,000. In sensitivity analysis, reducing the cost of BEV by 13% (from $9,338 to $8,100 per cycle) allows 10-mg/kg dosing to reach a $100,000 ICER. Exploratory analysis of different BEV chemotherapy partners showed an ICER of $76,000 per progression-free LYS (6.5-month progression-free survival improvement) and $54,000 per LYS (9.1-month overall survival improvement) for the addition of BEV to paclitaxel once per week. Using the ASCO framework for value assessment, the NHB score for BEV plus paclitaxel once per week is 48. Conclusion: Using a willingness-to-pay threshold of $100,000 ICER, the addition of BEV to chemotherapy either demonstrates or approaches cost-effectiveness and NHB when added to the treatment of patients with PROC.


2008 ◽  
Vol 26 (22) ◽  
pp. 3791-3796 ◽  
Author(s):  
Lori E. Dodd ◽  
Edward L. Korn ◽  
Boris Freidlin ◽  
C. Carl Jaffe ◽  
Lawrence V. Rubinstein ◽  
...  

Progression-free survival is an important end point in advanced disease settings. Blinded independent central review (BICR) of progression in randomized clinical trials has been advocated to control bias that might result from errors in progression assessments. However, although BICR lessens some potential biases, it does not remove all biases from evaluations of treatment effectiveness. In fact, as typically conducted, BICRs may introduce bias because of informative censoring, which results from having to censor unconfirmed locally determined progressions. In this article, we discuss the rationale for BICR and different ways of implementing independent review. We discuss the limitations of these approaches and review published trials that report implementing BICR. We demonstrate the existence of informative censoring using data from a randomized phase II trial. We conclude that double-blinded trials with consistent application of measurement criteria are the best means of ensuring unbiased trial results. When such designs are not practical, BICR is not recommended as a general strategy for reducing bias. However, BICR may be useful as an auditing tool to assess the reliability of marginally positive results.


2007 ◽  
Vol 25 (13) ◽  
pp. 1670-1676 ◽  
Author(s):  
Alfredo Falcone ◽  
Sergio Ricci ◽  
Isa Brunetti ◽  
Elisabetta Pfanner ◽  
Giacomo Allegrini ◽  
...  

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 561-561
Author(s):  
S. Yuki ◽  
K. Shitara ◽  
M. Yoshida ◽  
D. Takahari ◽  
S. Utsunomiya ◽  
...  

561 Background: Weekly cetuximab and irinotecan is a standard regimen in heavily pretreated patients with metastatic colorectal cancer (MCRC). The aim of this study was to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pretreated MCRC harboring wild-type KRAS. Methods: Patients with wild- type KRAS MCRC that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included in this study. Cetuximab was administered at 500 mg/m2 biweekly with irinotecan. The primary endpoint was response rate. The secondary endpoints included adverse events, progression-free survival, and overall survival. The pharmacokinetics of cetuximab was also evaluated in five patients. Results: From May, 2009 to February, 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 assessable patients, ECOG PS was 0 in 12, 1 in 16, and 2 in two patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7-49.4), and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95%CI, 61.4-92.3). The median progression-free survival was 5.3 months (95%CI, 3.4-7.3). Grade 3 skin toxicity was observed in 3 patients (10%), and treatment related death due to pneumonia occurred in one patient. Conclusions: The efficacy data are similar to those of standard dose of cetuximab plus irinotecan. Combination chemotherapy with biweekly cetuximab and irinotecan is effective for pretreated metastatic wild-type KRAS MCRC. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14066-e14066
Author(s):  
Florian Eisner ◽  
Michael Stotz ◽  
Hellmut Samonigg ◽  
Sigurd Lax ◽  
Gerald Hoefler ◽  
...  

e14066 Background: MicroRNA-143 is frequently down-regulated in colorectal cancer (CRC) and influence CRC cell proliferation, apoptosis and sensitivity to 5-fluorouracil. mRNA encoded by the KRAS oncogene has been identified as a target of microRNA-143. However, the prognostic significance of microRNA-143 expression and the ability to predict the patient response to EGFR-targeted agents have not been explored yet. Methods: In this study, we analyzed 77 CRC harboring wild-type KRAS and obtaining treatment with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. MicroRNA-143 expression was measured by RT-PCR in both CRC and corresponding non-neoplastic colon tissue and the expression levels were correlated with clinico-pathological characteristics. Cancer-specific survival was calculated by uni- and multivariate analyses. The progression-free survival and objective response rates on EGFR-targeted therapy were also evaluated. Results: Down-regulation of microRNA-143 was observed in 47/77 (61%) CRC. Multivariate Cox regression analysis identified low levels of microRNA-143 expression as an independent prognostic factor with respect to cancer-specific survival (HR=1.92, CI=1.1-3.4, p=0.024). A significant difference was observed with respect to progression-free survival on EGFR-targeted therapy (p=0.031, log-rank test), but there were no significant differences with regard to the objective response rate. Conclusions: Our data suggest that microRNA-143 expression levels serve as independent prognostic biomarker for KRAS wild-type CRC patients but not as predictor for EGFR-targeted therapy. In addition, we consider microRNA-143 as a potential drug target for future therapy of CRC.


2012 ◽  
Vol 6 ◽  
pp. CMO.S7432 ◽  
Author(s):  
Tzu-Fei Wang ◽  
Albert Craig Lockhart

Colorectal cancer is the third most common cancer in the US. In recent decades, an improved understanding of the role of the angiogenesis pathway in colorectal cancer has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic colorectal cancer, and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. Here we review the role of angiogenesis in the tumorigenesis of colorectal cancer, strategies for targeting angiogenesis, and the clinical development of aflibercept.


2010 ◽  
Vol 14 (Suppl 2) ◽  
pp. 47-53
Author(s):  
S Whyte ◽  
A Pandor ◽  
M Stevenson ◽  
A Rees

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer based on the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one phase III, multicentre, multinational, randomised, open-label study (NO16966 trial). This two-arm study was originally designed to demonstrate the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil plus folinic acid plus oxaliplatin (FOLFOX)-4 in adult patients with histologically confirmed metastatic colorectal cancer who had not previously been treated. Following randomisation of 634 patients, the open-label study was amended to include a 2 × 2 factorial randomised (partially blinded for bevacizumab) phase III trial with the coprimary objective of demonstrating superiority of bevacizumab in combination with chemotherapy compared with chemotherapy alone. Measured outcomes included overall survival, progression-free survival, response rate, adverse effects of treatment and health-related quality of life. The manufacturer’s primary pooled analysis of superiority (using the intention-to-treat population) showed that after a median follow-up of 28 months, the addition of bevacizumab to chemotherapy significantly improved progression-free survival and overall survival compared with chemotherapy alone in adult patients with histologically confirmed metastatic colorectal cancer who were not previously treated [median progression-free survival 9.4 vs 7.7 months (absolute difference 1.7 months); hazard ratio (HR) 0.79, 97.5% confidence interval (CI) 0.72 to 0.87; p = 0.0001; median overall survival 21.2 vs 18.9 months (absolute difference 2.3 months); HR 0.83, 97.5% CI 0.74 to 0.93; p = 0.0019]. The NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free survival and overall survival when bevacizumab was added to XELOX or FOLFOX. However, the size of the actual treatment effect of bevacizumab is uncertain. The ERG believed that the modelling structure employed was appropriate, but highlighted several key issues and areas of uncertainty. At the time of writing, NICE was yet to issue the guidance for this appraisal.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1715
Author(s):  
Hiroya Taniguchi ◽  
Takeharu Yamanaka ◽  
Daisuke Sakai ◽  
Kei Muro ◽  
Kentaro Yamazaki ◽  
...  

Background: Phase-III ASPECCT and randomised phase-II WJOG6510G trials demonstrated the noninferiority of panitumumab, when compared with cetuximab, for overall survival in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. Methods: The subgroup that received bevacizumab either prior to panitumumab or cetuximab monotherapy (ASPECCT) or in combination with irinotecan (WJOG6510G) was included. Multivariate Cox models were created, including the treatment arms as covariates together with patient, disease and treatment characteristics. Results: We included 185 and 189 patients in the panitumumab and cetuximab arms, respectively. The median overall survival was 12.8 and 10.1 months [p = 0.0031; log-rank test, stratified by trial; hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90], and the median progression-free survival was 4.7 and 4.1 months, in the panitumumab and cetuximab arms, respectively (p = 0.0207; HR, 0.79; 95% CI, 0.64–0.97). The treatment regimen was an independent prognostic factor of overall survival (adjusted HR, 0.69; 95% CI, 0.54–0.87; p = 0.0013). Conclusions: Panitumumab significantly prolonged the overall survival and progression-free survival, when compared with cetuximab in the cohort that previously received bevacizumab in the included studies. Clinical Trial Registration: ASPECCT trial registered with ClinicalTrials.gov (NCT01001377) and WJOG6510G trial registered with UMIN-CTR (UMIN000006643).


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