Abstract 789P
Background
We evaluated the prevalence and prognostic value of PD-L1 and TMB in SOC-treated advanced cervical cancer.
Methods
Patients had persistent, recurrent, or metastatic cervical cancer diagnosed from January 2008 to December 2016 at Asan Medical Center in South Korea. Clinical data were retrospectively collected from medical records; archived tumor samples were tested in a central laboratory. PD-L1 expression by IHC was based on combined positive score (CPS) ≥1. TMB was assessed by whole exome sequencing with a cutoff of ≥175 mut/exome (equivalent to 10 mut/Mb by FoundationOne®CDx). OS was calculated from advanced diagnosis or 1L or 2L systemic therapy initiation until death or last follow-up. Association between OS and PD-L1 and TMB was analyzed using log-rank test and Cox proportional hazard models adjusted for age, stage, prior treatment, comorbidities, and other characteristics.
Results
Of 267 pts, 76.0% had squamous cell carcinoma (SCC), 24.0% adenocarcinoma or adenosquamous carcinoma (AC/AS), 64.4% PD-L1 CPS ≥1, and 32.6% TMB ≥175 mut/exome. PD-L1 CPS ≥1 and TMB ≥175 mut/exome were more prevalent in SCC than in AC/AS (73.9% and 37.2% vs 34.4% and 17.7%). The most common 1L treatments were carboplatin/paclitaxel (62%), cisplatin/paclitaxel/bevacizumab (17%), and cisplatin/paclitaxel (12.6%). No pts received immunotherapy. There was no association between OS and PD-L1 (CPS ≥1 vs <1; adjusted HR [95% CI]: 1.09 [0.80-1.47] from advanced diagnosis; 1.05 [0.77-1.43] from 1L initiation; 1.04 [0.74-1.46] from 2L initiation). There was a negative association between OS and TMB (≥175 vs <175 mut/exome; adjusted HR [95% CI]: 1.27 [0.93-1.73] from advanced diagnosis; 1.45 [1.05-1.99] from 1L initiation; 1.54 [1.06-2.23] from 2L initiation). PD-L1 and TMB were not correlated (P=0.75). Similar results were seen in subgroups by histology, recurrent/metastatic disease, adjuvant treatment, or use of 1L bevacizumab.
Conclusions
In this retrospective analysis of pts with SOC-treated advanced cervical cancer, higher prevalence of PD-L1 CPS ≥1 and TMB ≥175 mut/exome was observed in SCC versus AC/AS. PD-L1 CPS ≥1 was not associated with OS; TMB ≥175 mut/exome may be associated with worse OS. Further studies are warranted to confirm these findings.
Clinical trial identification
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Dominic Singson, MD, and Holly Cappelli, PhD, CMPP, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
L. Chen: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck; Financial Interests, Personal and Institutional, Stocks/Shares: Merck. P. Jelinic: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck; Financial Interests, Personal and Institutional, Stocks/Shares: Merck. R. Cristescu: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck; Financial Interests, Personal, Other, Patents Pending: Self. X.Y. Jin: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck. C. Shao: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck; Financial Interests, Personal and Institutional, Stocks/Shares: Merck. C. Tekin: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck; Financial Interests, Personal and Institutional, Stocks/Shares: Merck. All other authors have declared no conflicts of interest.