Abstract 725P
Background
The presence of tumor infiltrating lymphocytes (TILs) is considered a poor prognostic marker in renal cell carcinoma (RCC), unlike in other tumors. We previously investigated prognostic impact of PD-L1 status in RCC after the start of systemic therapy, and found that the prognostic impact of PD-L1 status showed different trends in subgroup of immune phenotype (classification based on spatial localization of CD8+ T cells: Inflamed [I], Excluded [E], Desert [D]).
Methods
We analyzed 770 patients for both PD-L1 expression (expression in immune cells [IC] by the SP142 scoring method) and immune phenotype. Of these, 389 patients were also tested with SP263 IHC assay, and we evaluated the concordance of these two antibodies. Overall survival (OS), defined as the time from nephrectomy to death from any cause, was evaluated. The hazard ratio (HR) for PD-L1-positive (IC ≥1%) versus PD-L1-negative status and confidence interval (CI) were estimated by the Cox proportional hazard model. OS according to PD-L1 status and immune phenotype were analyzed.
Results
Of the 770 patients, PD-L1 positivity on SP142 was observed in 315 (40.9%). The 770 patients were classified into immune phenotypes I (59 [7.7%]), E (378 [49.1%]), or D (333 [43.2%]). PD-L1 positivity was strongly associated with immune phenotype: I (88.1%), E (61.9%), D (8.7%). Median OS (mOS) in PD-L1-positive (PD-L1+) vs -negative (PD-L1−) patients was 41.5 vs 67.8 months (HR 1.48 [95%CI 1.23–1.77]). The mOS in I vs E vs D was 28.8 vs 57.3 vs 63.4 months (HR of I vs D 1.78 [95%CI 1.27–2.49]; HR of E vs D 1.08 [95%CI 0.89–1.30]). Compared to mOS of 67.2 months in PD-L1–/D (n=304) used as a reference, PD-L1−/E (n=144) showed similar mOS of 78.1 months (HR 0.92 [95%CI 0.72–1.19]); however, PD-L1+/E (n=234) showed shorter mOS of 48.2 months (HR 1.32 [95%CI 1.06–1.63]). Of 389 patients tested with both SP142 and SP263, 163 (41.9%) were positive on SP142 and 219 (56.3%) were positive on SP263. The overall percentage agreement of SP263 with SP142 (IC1% cut off) was 83% (PPA 97%, NPA 73%).
Conclusions
Our study suggested that PD-L1 expression and immune phenotype are highly related. SP142 and SP263 showed a certain level of concordance based on the IC1% cut off.
Clinical trial identification
UMIN000034131/NCT03748901.
Editorial acknowledgement
Legal entity responsible for the study
Chugai Pharmaceutical Co., Ltd.
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
T. Tsuzuki: Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai pharma; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Janssen; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self): Nippon Kayaku; Honoraria (self): Astellas Pharma; Honoraria (self): Bayer; Honoraria (self): Takeda; Honoraria (self): Daiichi Sankyo. C. Ohe: Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Chugai pharmaceutical co.ltd; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca K.K.; Honoraria (self): Janssen Pharmaceutical K.K.. T. Yoshimoto: Full/Part-time employment: Chugai pharmaceutical co.ltd. Y. Nakagawa: Full/Part-time employment: Chugai pharmaceutical co.ltd. T. Fukuyama: Full/Part-time employment: Chugai pharmaceutical co.ltd. N. Matsubara: Advisory/Consultancy, Research grant/Funding (institution): Janssen; Research grant/Funding (institution): MSD; Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Chugai Pharmaceuticals. G. Kimura: Honoraria (self), Research grant/Funding (institution): Chugai pharmaceutical co.ltd; Honoraria (self), Research grant/Funding (institution): Ono pharmaceutical; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Janssen; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Novartis. H. Uemura: Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: MSD; Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Janssen; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Astellas Pharma; Honoraria (self): Bayer; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Taiho Pharmaceutical. All other authors have declared no conflicts of interest.