PD-L1 Expression in Locally Advanced Cervical Cancer: A Pilot Cross-Clone Comparison Study

Recent immunotherapy trials of locally advanced cervical cancer report high PD-L1 positivity rates, whereas academic multicenter initiatives report lower PD-L1 positivity rates. These observations necessitate a cross-clone comparison to understand the observed differences.

Two different clones, SP142 (BIOEMBRACE) and 22C3 (KEYNOTE-A18), used in previous multicenter international studies, were used to test PD-L1 positivity in a pilot cohort of International Federation of Gynecology and Obstetrics 2018 stage III cervical cancer patients recruited for a phase 3 trial. SP-142 immunohistochemistry (IHC) results were already available, and negative and positive samples were included in a 2:1 ratio. Biopsy material was processed for PD-L1 IHC using the clone 22C3 pharmDx combined positive score (combined positive score ≥ 1), with either antibody considered positive. Positive and negative predictive values were calculated for each antibody while using the other as the reference.

In this study, 20 PD-L1-negative and 10 PD-L1-positive (SP142) samples were included. The pilot positivity of the a priori selected cohort was 33.3%. The PD-L1 positivity rate was 36.6% (11/30) using 22C3. Among the 20 SP142-negative patients, 6 patient samples (30%) tested positive on PD-L1 IHC with 22C3, leading to a 70% negative predictive rate for SP142. Five patient samples that were positive for SP142 did not test positive for 22C3, leading to a positive predictive value of 50% when presuming 22C3 as the reference standard. The positive and negative predictive values of 22C3 (while taking SP142 as a reference) were 45% and 73% respectively.

Our findings highlight the differences in PD-L1 expression when different antibody clones are used for PD-L1 IHC. Though the overall positivity rate was not different, there was heterogeneity at the per-patient level. Further investigation into PD-L1 expression is needed.