Investigation of PD-L1 expression and response to pembrolizumab (pembro) in gastric cancer (GC) and cervical cancer (CC) using combined positive score (CPS) and tumor proportion score (TPS).

4065 Background: TPS, the percentage of viable tumor cells with partial or complete membrane staining at any intensity, has been invaluable for assessing PD-L1 expression in non–small cell lung cancer (NSCLC) and identifying patients (pts) likely to respond to anti-PD–1/PD-L1 therapy. However, TPS has limited utility beyond NSCLC. We investigated the predictive value of TPS and CPS and their association with response to pembro in pts with GC and CC. Methods: Tumor samples from pts with previously treated GC (KEYNOTE-059, NCT02335411) or CC (KEYNOTE-158, NCT02628067) were analyzed for PD-L1 expression per an investigational-use-only-labeled version of the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies). Response was assessed per RECIST v1.1 by independent review. External reproducibility of CPS, the number of PD-L1–staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100, was assessed. Results: Response, prevalence, positive predictive value (PPV), and negative predictive value (NPV) for CPS and TPS at cutoffs of 1 (TPS1, CPS1) and 10 (TPS10, CPS10) are shown in the table. Response to pembro was significantly associated with CPS (P= 0.002) but not TPS (P= 0.224) in GC, whereas response to pembro was significantly associated with CPS (P= 0.008) and TPS (P= 0.023) in CC. Intersite and interobserver overall agreement assessments of external reproducibility for CPS were 92.0% (95% CI, 87.4-96.3) and 96.6% (95% CI, 94.0-98.7), respectively, in GC and 95.0% (95% CI, 90.3-99.2) and 99.7% (95% CI, 99.7-100.0), respectively, in CC. Conclusions: CPS is a robust, reproducible scoring method that identified more responders than did TPS in GC and CC. Further investigation of CPS in cancers beyond NSCLC is warranted. Clinical trial information: NCT02335411 and NCT02628067.Scoring and Cutoff Responders/Total n/N Prevalence of PD-L1 Expression, % PPV, % NPV, % Odds ratio for Tumor Response All Patients, N PD-L1 Positive PD-L1 Negative Gastric cancer CPS1 257 24/148 7/109 58 16 94 2.8 TPS1 5/32 26/225 12 16 88 1.4 Cervical cancer CPS1 96 13/81 0/15 84 16 100 ∞ TPS1 10/50 3/46 52 20 93 3.6 CPS10 10/45 3/51 47 22 94 4.6 TPS10 6/26 7/70 27 23 90 2.7