Abstract 729P
Background
PD-1/PD-L1 blockade is currently being investigated as adjuvant therapy in localized RCC; however, the role of PD-1/PD-L1 in this setting is not yet clear. In a multicenter retrospective study we evaluated PD-L1 status in 770 patients with metastatic or recurrent RCC treated by systemic therapy (ARCHERY study). Here we examined the subset with recurrent RCC.
Methods
Of 770 patients, we analyzed 381 with localized RCC who had undergone radical nephrectomy (RN) but had subsequent recurrence. Time to recurrence (TTR) defined as time from RN to date of recurrence and overall survival (OS) defined as time from RN to death from any cause, were evaluated. Hazard ratio (HR) for PD-L1-positive status (as evaluated by the VENTANA SP142 immune cell scoring method) vs PD-L1-negative status and confidence interval (CI) was estimated by the Cox proportional hazard model. We performed a subgroup analysis based on defined High risk (n=201) and Low risk (n=160) subgroups based on clinical stage and Fuhrman grade.
Results
Of the 381 patients, 120 (31.5%) were PD-L1-positive. Clinical stage and Fuhrman grade distribution in PD-L1-positive vs –negative was as below; Stage I+II (36.7% vs 45.6%) / III+IV (59.2% vs 48.7%), Fuhrman Gr2 (18.3% vs 49.0%) / Gr3 (58.3% vs 44.4%) / Gr4 (22.5% vs 6.1%). Both TTR and OS were worse in PD-L1-positive than -negative patients: TTR HR 1.46 (95%CI 1.17–1.81), median TTR 12.1 vs 21.9 months; OS HR 1.32 (95%CI 1.00–1.75), median OS 75.8 vs 97.7 months. In both High and Low risk subgroups PD-L1-positive patients had shorter TTR: In the High risk group median TTR was 7.6 vs 15.3 months (HR 1.49 [95%CI 1.11–2.00]); in the Low risk group it was 24.1 vs 29.3 months (HR 1.26 [95%CI 0.88–1.80]). In the High risk group (but not the Low risk group) PD-L1-positive patients had shorter OS: In the High risk group median OS was 55.2 vs 83.5 months (HR 1.53 [95%CI 1.06–2.21]); in the Low risk group it was 94.6 vs 110.9 months (HR 1.05 [95%CI 0.66–1.68]).
Conclusions
Our results suggest that PD-L1 expression may play a role in recurrence risk and OS, especially in high-risk patients. Of note, nuclear grade was found to be higher in PD-L1-positive patients, which merits further investigation.
Clinical trial identification
UMIN000034131/NCT03748901.
Editorial acknowledgement
Legal entity responsible for the study
Chugai Pharmaceutical Co., Ltd.
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
M. Nozawa: Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Novartis. S. Tamada: Research grant/Funding (institution): Chugai pharmaceutical co.ltd; Speaker Bureau/Expert testimony: Pfizer. R. Mizuno: Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Ono Pharmaceuticals; Honoraria (self): Bristol-Myers Squibb. C. Ohe: Research grant/Funding (self): Chugai pharmaceutical co.ltd. 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; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): BMS; 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. Y. Tomita: Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Ono pharmaceutical; Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Astellas; Honoraria (self): Novartis; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Chugai pharmaceutical. N. Nonomura: Honoraria (self), Research grant/Funding (institution): Ono Pharnaceuticals; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Novartis Pharma; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceuticals. M. Eto: Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): Chugai pharmaceutical Co., Ltd.; Honoraria (institution): Janssen; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; Research grant/Funding (self): Astellas Pharma; Research grant/Funding (institution): Bayer; Honoraria (self), Research grant/Funding (self): Takeda; Research grant/Funding (institution): Sanofi; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Research grant/Funding (self): Kissei. All other authors have declared no conflicts of interest.