Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma.
https://www.ncbi.nlm.nih.gov/pubmed/28988341
https://static-content.springer.com/esm/art%3A10.1007%2Fs11060-017-2629-z/MediaObjects/11060_2017_2629_MOESM1_ESM.docx
Axitinib improves response rate and progression-free survival in patients with rGBM compared to historical controls. There is no indication that upfront combination of axitinib with CCNU improves results.
From this study does not follow that instead of Lomustin it is better to take Axitinib?
I need to decide what to add to Bevacizumab for my mom.
Axitinib is a kinase inhibitor targeting VEGFR receptors. Bevacizumab is an antibody against VEGF-A. Their mechanisms are therefore overlapping, and you'd have a hard time convincing an oncologist or institution to use two different (and expensive) drugs with highly overlapping mechanisms of action.
ReplyDeleteIn this trial, the addition of lomustine to axitinib didn't improve outcomes in the general population, but results aren't given specifically for the patients with MGMT-methylated status, who would be more likely to benefit from lomustine.
The phase 3 EORTC 26101 trial had an arm receiving lomustine alone, and an arm receiving BEV + lomustine, but there was no arm receiving only BEV. In the MGMT-methylated group in this trial, adding BEV to lomustine led to much better PFS and marginally better OS (hazard ratio = 0.72).
http://www.nejm.org/doi/full/10.1056/NEJMoa1707358
In the randomized phase 2 BELOB trial,
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70314-6/abstract
there was an arm receiving BEV only, an arm receiving lomustine only, and a third arm receiving the combination. For the MGMT-methylated patients, the combination led to much better PFS than either drug alone, while 9-month overall survival rates were 52% (lomustine alone), 67% (BEV alone), and 67% (combination). However with longer follow-up to one and two years, it's possible that overall survival for the combination-treated MGMT-methylated patients could have been superior, as it was for progression-free survival.
In my view the combination of lomustine + BEV makes sense for MGMT-methylated patients, who can expect at least longer progression-free survival with the combination than with either drug alone.
Axitinib seems to have activity, and like BEV it targets the VEGF/VEGFR axis, and could be used as an alternative to BEV, though I've not seen any trial doing a direct comparison between BEV and axitinib.
Thank you very much for such a detailed analysis!
DeleteWhat about this study?
DeleteRandomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma.
2016 https://www.ncbi.nlm.nih.gov/pubmed/26935577
"Forty-four patients were randomly assigned to receive treatment with axitinib (5 mg BID starting dose; N = 22) or "physicians best alternative choice of therapy" that consisted of bevacizumab (N = 20) or lomustine (N = 2). Six-month progression-free survival served as the primary endpoint. The estimated 6-month progression-free survival rate was 34 % (95 % CI 14-54) for patients treated with axitinib and 28 % (95 % CI 8-48) with best alternative treatment; median overall survival was 29 and 17 weeks, respectively. Objective responses according to RANO criteria were documented in 28 % of patients treated with axitinib and 23 % of patients treated with best alternative therapy. A decrease in maximal uptake of 18F-fluoro-ethyL-tyrosine (18F-FET) by the glioblastoma on PET imaging was documented in 85 % of patients at the time of response on axitinib. Corticosteroid treatment could be stopped in four and tapered in seven out of the 15 patients who were treated with steroids at baseline in the axitinib cohort. Most frequent axitinib related grade ≥3 adverse events consisted of fatigue (9 %), diarrhea (9 %), and oral hyperesthesia (4.5 %). We conclude that axitinib has single-agent clinical activity and a manageable toxicity profile in patients with recurrent glioblastoma."
It is important to know, can axinitis be the next line after failure of bezacizumab + lomustine ??
If bevacizumab (antibody against VEGF-A) stops working, I wouldn't be very confident that axitinib (targeting VEGF receptors) would be useful in that situation.
Delete