Abstract B193: PD-L1 somatic alterations predict sensitivity of advanced prostate cancer patients to platinum-based chemotherapy
Authors: Vlachostergios Panagiotis J. , Lee Aileen , Thomas Charlene , Patel Priyanka , Hackett Amy L. , Rashid Naureen , Molina Ana M. , Nanus David M. , Beltran Himisha , Tagawa Scott T. 
Published: February 2019

Background: The immune contexture of cancers and the tumor-immune system interplay are becoming increasingly understood. Immunotherapy with checkpoint inhibitors is an established treatment for several cancer types, with PD-L1 immunohistochemical expression as a companion predictive biomarker in some tumors. Checkpoint blockade is not an established treatment for patients with advanced PC (castration-resistant or neuroendocrine); however, platinum compounds have shown activity. The aim of this study was to assess the impact of PD-L1 somatic alterations on clinical response to platinum-based chemotherapy in men with advanced PC. Methods: Records of advanced PC patients from our Precision Medicine cohort who were treated with platinum-containing chemotherapy with available tissue samples and information on known prognostic factors were reviewed. By whole-exome sequencing (WES) we assessed for presence of mutations and copy number alterations in CD274 gene (encoding PD-L1). Kaplan Meier curves, univariable and multivariable Cox regression analyses were used to predict time to PSA progression-free survival (PSA-PFS), radiographic progression-free (rPFS) and overall survival (OS) after platinum chemotherapy initiation. Results: Thirty-one men, median age 69 years (range 50-85), were studied. Eight patients (26%) were NEPC based on histologic features. Nineteen had visceral metastases (16 liver, 11 lung, 1 brain) and 25 had bone metastases. 26 patients received carboplatin, 8 received cisplatin (4 received both sequentially, with initial platinum used for this analysis). Most received platinum in combination with other drugs, most commonly paclitaxel (N=11) and etoposide (N=12). CD274 somatic alterations (mutations or/and copy number changes) were associated with a significantly longer rPFS (median rPFS: 8 months) compared to patients with wild-type PD-L1 (median rPFS: 4 months, P=0.022). PD-L1 alterations were less frequent in patients with bone metastases (2/22 vs 4/9, P=0.043). There was no significant difference in PSA-PFS or OS among patients with PD-L1 wild-type and mutated tumors. On multivariate analysis (adjusted for Gleason score, PSA, alkaline phosphatase, lactate dehydrogenase, hemoglobin, visceral metastases, performance status, use of opioids), PSA (P=0.049) and presence of visceral metastases (P=0.048) were independent prognostic indicators for OS. Conclusions: PD-L1 somatic alterations may confer sensitivity to platinum-based chemotherapy in men with advanced PC who receive platinum-based chemotherapy. Prospective validation studies in such patients are needed to confirm these findings.

Citation Format: Panagiotis J. Vlachostergios, Aileen Lee, Charlene Thomas, Priyanka Patel, Amy L. Hackett, Naureen Rashid, Ana M. Molina, David M. Nanus, Himisha Beltran, Scott T. Tagawa. PD-L1 somatic alterations predict sensitivity of advanced prostate cancer patients to platinum-based chemotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B193.