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Table of Contents
LETTER TO EDITOR
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 579-580

The cost containment strategy by optimizing the bevacizumab dose for glioblastoma: Worthy or not?


Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

Date of Submission12-Aug-2021
Date of Decision15-Aug-2021
Date of Acceptance19-Aug-2021
Date of Web Publication08-Oct-2021

Correspondence Address:
Srujana Joga
Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, Sector 5, New Delhi - 110 085
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_190_21

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How to cite this article:
Jain A, Joga S, Patel AB. The cost containment strategy by optimizing the bevacizumab dose for glioblastoma: Worthy or not?. Cancer Res Stat Treat 2021;4:579-80

How to cite this URL:
Jain A, Joga S, Patel AB. The cost containment strategy by optimizing the bevacizumab dose for glioblastoma: Worthy or not?. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Dec 9];4:579-80. Available from: https://www.crstonline.com/text.asp?2021/4/3/579/327780



We read the article titled, “Optimal dose of bevacizumab in recurrent glioma: A retrospective study” by D'souza et al. and the accompanying editorial with great interest.[1],[2]

We would like to congratulate the author for introducing the thought process of optimizing the dose of bevacizumab in patients with glioblastoma multiforme (GBM) while maintaining comparable efficacy, reducing the toxicity, and addressing the financial issue in a lower-middle-income economy country like India.

Bevacizumab, a humanized monoclonal antibody targeting the vascular endothelial growth factor, received accelerated approval by the Food and Drug Administration for the treatment of recurrent GBM in 2009. Bevacizumab did not result in an overall survival (OS) benefit when used as monotherapy. Two phase III randomized prospective trials, AVAglio[3] and RTOG 0825,[4] demonstrated the efficacy of bevacizumab in the first-line setting for glioblastoma. Progression-free survival was improved; safety and tolerability were acceptable; and health-related quality of life was maintained in the AVAglio trial, but not in RTOG-0825. However, there was no significant improvement in OS.

Data available from various clinical trials showed that the metabolic profile and pharmacokinetic (PK) parameters of bevacizumab were similar to those expected for an endogenous IgG1 molecule. Bevacizumab PK studies revealed a long terminal half-life, low clearance, and a limited central compartment volume of distribution (Vc).[5] This results in the minimum steady-state concentration and target therapeutic bevacizumab plasma level which are similar with a range of administration schedules (such as 5–10 mg/kg once every 2 or 3 weeks). The optimal dosing schedule of bevacizumab in patients with GBM is still debated.

Being a retrospective study, potential confounders and selection bias could have impacted the outcome. The two comparator arms were not matched with regard to some of the tumor-and treatment-related factors. There were 33.8% versus 66.2% patients (P = 0.002) randomized to the low dose versus standard dose bevacizumab groups, respectively. Patients with isocitrate dehydrogenase (IDH)-mutated glioma have a favorable disease outcome compared to the wild-type disease. Patients with IDH-mutated tumors constituted 43.5% versus 17.8% (P = 0.04) of the low dose versus standard dose bevacizumab groups, respectively.

Histopathology at baseline was also skewed; there were 75.6% patients with GBM (a well-known worse prognostic entity) in the low dose group versus 34.8% in the standard dose group (P = 0.002).

Comparison of the impact of low dose bevacizumab on patient reported outcome measures by assessing fatigue, health-related quality of life, anxiety, depression, and impairment in subjective neurocognitive function using tools such as European Organization for Research and Treatment of Cancer quality of life questionnaire core-30, the Mini–Mental State Examination, plus a neurocognitive test battery (NOA-07) should have been reported.

Subgroup analysis of this study could encompass a comprehensive economic assessment of administering low dose bevacizumab by both a cost-effectiveness analysis and a budget impact analysis; this would give a more realistic impression of the financial benefit in a non-reimbursement driven health-care system.

In conclusion, we agree that low dose bevacizumab could be a reasonable alternative to the standard dose regimen considering the equivalent survival outcome, relatively fewer toxicity events, and a generous benefaction; however, more well-designed, prospective, comparative randomized controlled trials are required to provide strong evidence and a definitive answer on the optimal dosing of bevacizumab in patients with recurrent GBM.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
D'souza H, Singh GK, Menon N, Abhyankar A, Puranik A, Mahajan A, et al. Optimal dose of bevacizumab in recurrent glioma: A retrospective study. Cancer Res Stat Treat 2021;4:224-30.  Back to cited text no. 1
    
2.
Biswas A. Bevacizumab in progressive or recurrent glioblastoma: A quest for the optimal dosage. Cancer Res Stat Treat 2021;4:356-9.  Back to cited text no. 2
  [Full text]  
3.
Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 2014;370:709-22.  Back to cited text no. 3
    
4.
Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 2014;370:699-708.  Back to cited text no. 4
    
5.
Han K, Peyret T, Quartino A, Gosselin NH, Gururangan S, Casanova M, et al. Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation. Br J Clin Pharmacol 2016;81:148-60.  Back to cited text no. 5
    




 

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