Abstract 3640: 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)
Authors: Amaria Rodabe N. , Trinh Van A. , Gu Jun , McIntyre Susan , Cabala Carlos Torres , Simien Rinata , Diab Adi , Tawbi Hussein A. , Davies Michael A. , Wong Michael K. , Hwu Patrick , Glitza Isabella C. , Patel Sapna P. , Hwu Wen Jen 
Published: August 2018

Abstract
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 &gt;1%, vs. 6.5 mo and 12 mo in 4 pts with PD-L1 &lt;1%. 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.
GroupLDH &gt; upper limit normal (%)Prior CNS metastases (%)Prior anti CLTA-4 exposure (%)Number of anti PD-1 doses (#)Overall Responses CRs + PRs (%)Median PFS (mo)Median OS (mo)Group 1 BRAFi-naïve; anti-PD alone23.72317.912.530.8 + 25.6= 56.41021Group 2 BRAFi-naïve; combination37.9206.710.523.3 + 43.3 = 66.6 812.5Group 3 BRAFi- refractory; anti-PD alone254073.31637.8 + 17.8= 55.6925Group 4 BRAFi- refractory; combination17.644.172.711.529.4 + 5.9 = 35.3519
Citation Format: Rodabe N. Amaria, Van A. Trinh, Jun Gu, Susan McIntyre, Carlos Torres Cabala, Rinata Simien, Adi Diab, Hussein A. Tawbi, Michael A. Davies, Michael K. Wong, Patrick Hwu, Isabella C. Glitza, Sapna P. Patel, Wen Jen Hwu. 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) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3640.