Critical appraisal:Ahmed KA, Abuodeh YA, Echevarria MI, Arrington JA, Stallworth DG, Hogue C, et al 2016
Critical Appraisal
Ahmed KA, Abuodeh YA, Echevarria MI, Arrington JA, Stallworth DG, Hogue C, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy. Ann Oncol 2016 Dec;27(12):2288-2294 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27637745.
Key Facts
cohort study
To compare the intracranial control rate in patients treated with stereotactic radiosurgery for intact melanoma brain mets within 3 mo of the receipt of anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitors or conventional chemotherapy.
96
anti-CTLA-4: n=25
BRAF/MEKi: n=12
BRAFi: n=18
distant melanoma brain metastases
local melanoma brain metastases
systemic progression-free survival
overall survival from SRS and cranial mets diagnosis
>distant melanoma brain metastases:
- Significant differences were noted among the groups in distant melanoma brain mets control rates following SRS, p=0.008.
6mo distant melanoma brain mets:
anti-PD-1: 61%
anti-CTLA-4: 26%
BRAF/MEK inibitor: 53%
BRAF inhibitor: 30%
conventional chemotherapy: 15%
12mo distant melanoma brain mets:
anti-PD-1: 38%
anti-CTLA-4: 21%
BRAF/MEK inibitor: 20%
BRAF inhibitor: 8%
conventional chemotherapy: 5%
- Treatment with BRAF/MEK inhibitors or anti-PD-1 was found to be significant for distant melanoma brain mets (univariate)
- Treatment remained significant (multivariate)
- chemotherapy v anti-PD-1 HR 3.1 (95%CI 1.5-6.6), p=0.001
- chemotherapy v BRAF/MEK inhibitor HR 2.1 (95%CI 1.1-4.4), P=0.03
- No differences chemotherapy v BRAF inhibitor, p=0.27 OR chemotherapy v anti-CTLA-4, p=0.26 (multivariate)
improvement in distant melanoma brain mets in chemotherapy v immunotherapy (anti-PD-1 and anti-CTLA-4), HR 2.1 (95%CI 1.1-3.6), p=0.02 (multivariate)
no improvement in distant melanoma brain mets in chemotherapy v targeted (BRAF inhibitors and BRAF/MEK inhibitors, HR 1.2 (95%CI 0.71-2), p=0.51
>local melanoma brain metastases:
- No significant differences among the groups in local melanoma brain mets control rates, p=0.25
>systemic progression-free survival, p=0.04:
6mo systemic progression-free survival:
anti-PD-1: 41%
anti-CTLA-4: 36%
BRAF/MEK inibitor: 58%
BRAF inhibitor: 29%
conventional chemotherapy: 20%
12mo systemic progression-free survival:
anti-PD-1: 41%
anti-CTLA-4: 27%
BRAF/MEK inibitor: 39%
BRAF inhibitor: 12%
conventional chemotherapy: 5%
- Significantly improved OS on both univariate and multivariate:
(multivariate analysis)
anti-PD-1 v chemotherapy: 2.7 (95%CI 1.4-5.7), p=0.005
anti-CTLA-4 v chemotherapy: 2.5 (95%CI 1.3-5.0), p=0.007
BRAF/MEK inhibitors v chemotherapy: 2.5 (95%CI 1.2-5.5), p=0.02
>overall survival from SRS, p=0.01:
6mo OS from SRS:
anti-PD-1: 76%
anti-CTLA-4: 68%
BRAF/MEK inibitor: 83%
BRAF inhibitor: 52%
conventional chemotherapy: 60%
12mo OS from SRS:
anti-PD-1: 48%
anti-CTLA-4: 41%
BRAF/MEK inibitor: 65%
BRAF inhibitor: 24%
conventional chemotherapy: 10%
>overall survival from cranial mets diagnosis, p=0.004:
6mo OS from cranial mets:
anti-PD-1: 81%
anti-CTLA-4: 84%
BRAF/MEK inibitor: 83%
BRAF inhibitor: 71%
conventional chemotherapy: 70%
12mo OS from cranial mets:
anti-PD-1: 66%
anti-CTLA-4: 50%
BRAF/MEK inibitor: 75%
BRAF inhibitor: 29%
conventional chemotherapy: 15%
> Percentage, p=0.10:
Percentage demonstrating progression in the brain alone:
anti-PD-1: 16%
anti-CTLA-4: 19%
BRAF/MEK inibitor: 70%
BRAF inhibitor: 47%
conventional chemotherapy: 25%
Percentage demonstrating progression in systemic alone:
anti-PD-1: 33%
anti-CTLA-4: 19%
BRAF/MEK inibitor: 0%
BRAF inhibitor: 20%
conventional chemotherapy: 15%
Percentage demonstrating progression in both brain and systemic progression:
anti-PD-1: 50%
anti-CTLA-4: 63%
BRAF/MEK inibitor: 30%
BRAF inhibitor: 33%
conventional chemotherapy: 60%
no
Evidence ratings
III-2
High risk of bias | Comments: representative sample, most baseline variables were comparable, survival outcomes, all patients accounted for |
1 | Reason for decision: p<0.01 |
1 | Additional comments: patient-related outcomes |
- Article
- Ahmed KA, Abuodeh YA, Echevarria MI, Arrington JA, Stallworth DG, Hogue C, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy. Ann Oncol 2016 Dec;27(12):2288-2294 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27637745.
- Assigned to
- User:Cecilia.taing
- Topic area
- Guidelines:Melanoma
- Clinical question
Section below only relevant for Cancer Council Project Officer