Abstract A44: No tumor or very small tumor burden in on-treatment biopsies is significantly associated with response to Pembrolizumab
Authors: Xu Mingxuan , Ouyang Fengying , Alshawa Anas , Hajjar Joud , Castillo Lilibeth , Le Hung , Murthy Ravi , Naing Aung , Tapia Coya 
Published: February 2019

Background: In phase I clinical trials, baseline and on-treatment biopsies are increasingly performed to investigate biomarkers correlating, e.g., with therapy response. Prior to use these biopsies for expensive analysis, quality control (QC) is performed regarding, e.g., morphology, tumor content. However, studies to correlate the results obtained from QC evaluation with clinical outcomes are lacking. The purpose of this study was to determine if data from the QC process correlate with therapy response.

Method: We investigated 64 baseline and 50 on-treatment (C1D15-21) biopsies from 67 patients participating in an ongoing phase I clinical trial receiving pembrolizumab for their rare tumors such as e.g. adrenocortical carcinoma, angiosarcoma, alveolar rhabdomyosarcoma, carcinoma of unknown primary, epithelioid hemangioendothelioma, malignant neoplasm of tunica vaginalis, paraganglioma, penile carcinoma, pituitary tumor, renal medullary carcinoma, teratoma, and others. Baseline and the on-treatment biopsies were taken in &gt;90% from the same amenable tumor lesion. Matched biopsies were available in n= 48 (71.64%) and data on response was available for 54 (80.60%) patients. From all biopsies the tumor content was estimated by a pathologist on an H&E slide. Low tumor burden was defined as 0-10% tumor in the biopsy. If more than one biopsy was available, the average tumor content was calculated and used for analysis. Response was defined as stable disease or partial response.

Results: The average tumor content in all biopsies was 39%, 38% baseline and 39% on-treatment. No tumor was detected in 15 (13%) of all biopsies, in 7 baseline (11%) and 8 on-treatment biopsies (16%). Low tumor burden was detected in 29 (25%) of all biopsies, in 17 baseline (27%) and in 12 on-treatment biopsies (24%). In 71% (5/7) of baseline biopsies and in 50% (4/8) of on-treatment biopsies with no tumor, fibrosis or necrosis was present. In 88% (15/17) of baseline biopsies and 67% (8/12) of on-treatment biopsies with low tumor burden fibrosis or necrosis was present. Thirty percent (7/23) of patients with response had no tumor in their on-treatment biopsies. All non-responders had tumor in their on-treatment biopsy. Forty three (10/23) patients with a low tumor burden in their on-treatment biopsies showed response compared to 5% (1/21) of non-responders. Hence, no tumor (0%) or low tumor burden (0-10%) in on-treatment biopsies was significantly associated with response (p=0.006 and p=0.003).

Conclusion: Results obtained from the QC of clinical trial biopsies provide valuable information on tissue suitability for further analysis. In addition, we showed that an on-treatment biopsy with no tumor or very little tumor burden may predict partial or stable disease. Further studies to validate the role of tumor content in on-treatment biopsies in predicting response are warranted.

Citation Format: Mingxuan Xu, Fengying Ouyang, Anas Alshawa, Joud Hajjar, Lilibeth Castillo, Hung Le, Ravi Murthy, Aung Naing, Coya Tapia. No tumor or very small tumor burden in on-treatment biopsies is significantly associated with response to Pembrolizumab [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A44.