Thursday, May 31, 2018

BRAF Positive comparing treating with anti-PD-1 alone or combined with BRAF/MEKi

One of the MANY hard things in melanoma is simply picking a treatment option!  Here is some interesting data looking at whether or not to take anti-PD-1 alone or in combination WITH a BRAF/MEK inhibitor combo if your melanoma is BRAF positive. 

Treatment strategies using anti-PD1/PD-L1 (anti-PD) and BRAF/MEK inhibitor (BRAFi) therapy: a retrospective study comparing sequential vs. concurrent administration in BRAF-mutated metastatic melanoma (BMMM)Amaria, Trinh, Gu, McIntyre, et al. AACR. April 2018.

Background: It is unclear whether anti-PD and BRAFi therapy should be administered sequentially or concurrently in patients (pts) with BMMM, although clinical trials using varying strategies are ongoing. We performed a retrospective, single-center analysis of BMMM pts who received anti-PD therapy either sequentially or concurrent with BRAFi therapy. 

Methods: A total of 457 metastatic melanoma pts (excluding uveal) were treated with anti-PD therapy at MD Anderson Cancer Center from 11/2009-12/2015. Of those, 148 pts had BMMM and were categorized into 4 treatment groups: BRAFi-naïve treated with anti-PD alone (group 1) N=39 (26%); BRAFi-naive treated with combination therapy (group 2) N=30 (20%); BRAFi-refractory treated with anti-PD alone (group 3) N=45 (31%); and BRAFi-refractory treated with combination therapy (group 4) N=34 (23%). Clinical outcomes were analyzed and tabulated for each group. Pretreatment tissue samples were obtained for correlative biomarker immunohistochemistry (IHC) analyses. 

Results: BMMM pts with elevated LDH are more likely to receive upfront combination therapy. BRAFi-refractory pts have a higher incidence of brain metastases than BRAFi-naïve pts. The clinical outcomes of overall responses, median PFS and OS are provided in the table. Preliminary biomarker IHC analyses in 11 pts showed PD-L1 expression on the tumor cells correlated with median PFS and OS : 15 mo and 22 mo, respectively in 7 pts with PD-L1 greater than 1%, vs. 6.5 mo and 12 mo in 4 pts with PD-L1 less than1%. 

Conclusions: Single-agent anti-PD therapy is an effective strategy in BMMM pts who are either BRAFi-naïve or refractory. Combination therapy of anti-PD and BRAFi in either BRAFi-naïve or refractory BMMM did not appear to improve clinical outcomes. Confirmation data are needed from ongoing prospective randomized clinical trials.

Group 1, BRAFi-naive, anti-PD alone:  (N=39)
LDH greater than normal = 23.7
Prior CNS mets = 23
Prior ipi = 17.9
Number of anti-PD-1 doses = 12.5
Overall responses, CRs +PRs = 30.8 + 25.6 = 56.4
Median PFS = 10 months
Median OS =  21 months

Group 2, BRAFi-naive, combination:  (N=30)
LDH greater than normal = 37.9
Prior CNS mets =  20
Prior ipi =  6.7
Number of anti-PD-1 doses = 10.5
Overall responses, CRs +PRs =   23.3 + 43.3 = 66.6
Median PFS = 8 months
Median OS =  12.5 months

Group 3, BRAFi-refractory, anti-PD alone:  (N=45)
LDH greater than normal = 25
Prior CNS mets =  40
Prior ipi =  73.3
Number of anti-PD-1 doses = 16
Overall responses, CRs +PRs = 37.8 + 17.8 = 55.6
Median PFS = 9 months
Median OS =  25 months

Group 4, BRAFi-refractory, combination:  (N= 34)
LDH greater than normal = 17.6
Prior CNS mets = 44.1
Prior ipi =  72.7
Number of anti-PD-1 doses = 11.5
Overall responses, CRs +PRs = 29.4 + 5.9 = 35.3
Median PFS = 5 months
Median OS = 19 months

For what it's worth.... - c

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