Impact of PD-L1 combined positive score (CPS) on clinical response to nivolumab in patients with advanced esophageal squamous cell carcinoma.
Authors: Yuki Matsubara, Kazuhiro Toriyama, Shigenori Kadowaki, Takatsugu Ogata, Taiko Nakazawa, Kyoko Kato, Kazuki Nozawa, Yukiya Narita, Kazunori Honda, Toshiki Masuishi, Hideaki Bando, Masashi Ando, Masahiro Tajika, Waki Hosoda, Kei Muro
Journal: Journal of Clinical Oncology (2021)

e16045 Background: The ATTRACTION-3 trial showed that nivolumab (Nivo) significantly improved overall survival (OS) of patients (pts) with previously treated advanced esophageal squamous cell carcinoma (ESCC) regardless of tumor programmed cell death ligand-1 (PD-L1) expression assessed with tumor proportion score (TPS). On the other hand, pembrolizumab prolonged OS in advanced esophageal carcinoma pts with combined positive score (CPS) of ≥ 10 in the KEYNOTE-181 trial. Whether CPS can predict clinical outcome of Nivo in advanced ESCC pts remains unclear. Methods: We retrospectively evaluated advanced ESCC pts who received Nivo at a single institution between January 2014 and September 2020. The main eligibility criteria were as follows: refractory or intolerant to fluoropyrimidines and platinum, no prior anti-PD-1/PD-L1 antibody treatment, no comorbid malignancies, and available tissue specimens obtained before initiation of Nivo. PD-L1 immunostaining was performed using PD-L1 IHC 22C3 pharmDx assay, and the tumors were classified into three groups depending on CPS (≥ 10, 1–10, &lt; 1). The adjusted hazard ratios (aHRs) for progression-free survival (PFS) and OS were calculated using a multivariate Cox model that contained variables with p values &lt; 0.05 in the univariate analysis. Results: Among 69 pts, 50 were eligible (CPS ≥ 10/CPS 1–10/CPS &lt; 1, 23/18/9). Patient characteristics were as follows (CPS ≥ 10/CPS 1–10/CPS &lt; 1): age, ≥ 65, 70/67/67%; male, 83/67/78%; PS ≥ 1, 61/72/44%; second-line treatment, 65/61/56%; disease status, recurrent, 61/33/78%; prior esophagectomy, 65/33/44%; prior radiotherapy, 57/56/56%; prior taxane, 52/28/44%; the number of metastatic sites, ≥ 2, 48/61/89%; lymph node metastasis, 78/83/89%, lung metastasis, 26/22/56%; liver metastasis, 17/17/44%. Among 42 pts (84%) with disease progression after Nivo treatment, 24 pts received salvage-line chemotherapy. The adjustment factor for PFS was liver metastasis, while that for OS was not detected. The median PFS was 4.1 months (mo) in CPS ≥ 10 and 2.5 mo in CPS 1–10 (HR vs. CPS ≥ 10, 1.06; 95% CI, 0.51–2.17; p = 0.864; aHR, 1.15; 95% CI, 0.54–2.36; p = 0.713), and 1.4 mo in CPS &lt; 1 (HR vs. CPS ≥ 10, 3,78; 95% CI, 1.53–8.92; p = 0.005; aHR, 1.91; 95% CI, 0.67–5.39; p = 0.223). The median OS was 12.3 mo in CPS ≥ 10, 10.2 mo in CPS 1–10 (HR vs. CPS ≥ 10, 1.72; 95% CI, 0.75–4.00; p = 0.201), and 9.0 mo in CPS &lt; 1 (HR vs. CPS ≥ 10, 2.31; 95% CI, 0.92–5.69; p = 0.075). Objective response rate (CPS ≥ 10/CPS 1–10/CPS &lt; 1) in 40 pts who had measurable lesions were 32/25/0%, respectively. Conclusions: The pts with CPS of &lt; 1 did not respond to Nivo. Our study suggests that CPS is useful for predicting response to Nivo in pts with advanced ESCC.[Table: see text]