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Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors are immune checkpoint inhibitors widely used in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) and other cancers. There is a lack of understanding regarding which factors are associated with therapeutic response.To conduct a systematic literature review of trials reporting on factors associated with differential response to PD-1/PD-L1 inhibitors among patients diagnosed with metastatic ccRCC and quantitatively synthesize the magnitude to which each factor modified the response to PD-1/PD-L1 inhibitors.The MEDLINE and Cochrane Register of Trials databases were searched for studies published in English from 2006 onward. Searches were last run on September 3, 2019.This systematic review and meta-analysis assessed 662 phase 2/3 randomized clinical trials that provided subgroup analyses of any baseline characteristics regarding the treatment response to PD-1/PD-L1 inhibitors, alone or as part of a combination therapy, with respect to overall survival (OS) or progression-free survival (PFS) among patients with metastatic ccRCC.A novel quantitative approach was used to synthesize subgroup findings across trials. The ratio of the subgroup-specific hazard ratios (HRs) from each study were pooled using a random-effects meta-analysis whereby ratios of 1.00 would indicate that the subgroup-specific HRs were equal in magnitude.Main outcomes were OS and PFS.From an initial 662 reports, 7 trials were considered eligible for inclusion. Meta-analyses suggested the treatment response to PD-1/PD-L1 inhibitors in patients with metastatic ccRCC was significantly associated with age (OS: ratio of HR for age ≥75 years to HR for age65 years, 1.51; 95% CI, 1.01-2.26), PD-L1 expression (PFS: ratio of HR for PD-L1 1% to HR for PD-L1 ≥ 10%, 2.21; 95% CI, 1.14-4.27; ratio of HR for PD-L1 1% to HR for PD-L1 ≥ 1%, 1.36; 95% CI, 1.10-1.68), Memorial Sloan Kettering Cancer Center risk score (PFS: ratio of HR for immediate risk score to HR for poor risk score, 1.62; 95% CI, 1.14-2.29; ratio of HR for favorable risk score to HR for poor risk score, 1.53; 95% CI, 1.00-2.34; ratio of HR for favorable risk score to HR for intermediate risk score, 0.96; 95% CI, 0.70-1.30), and sarcomatoid tumor presence (PFS: ratio of HR for no sarcomatoid differentiation to HR for sarcomatoid differentiation, 1.54; 95% CI, 1.07-2.21).This analysis suggests that older age, low levels of PD-L1 expression, and the absence of sarcomatoid tumor differentiation are associated with a diminished response to anti-PD-1/PD-L1 immunotherapies with respect to survival outcomes among patients with metastatic ccRCC.

e17097 Background: PD-1/PD-L1 inhibitors are immune checkpoint inhibitors widely used in the treatment of metastatic renal cell carcinoma (mRCC) and other cancers. There is a lack of understanding regarding which factors predict response to these therapies. To address this gap, a systematic literature review and meta-analyses were conducted. The objectives of this study were to a) conduct a systematic literature review of studies examining factors that modify the clinical efficacy of PD-1 or PD-L1 inhibitors among patients diagnosed with mRCC and b) quantitatively synthesize the magnitude to which each predictive factor modifies the effect of PD-1/PD-L1 inhibitors. Methods: Electronic databases MEDLINE and COCHRANE were searched for studies published in English from 2006 onwards. We included all phase II/III randomized trials that provided subgroup analyses of any baseline characteristics regarding the effect of PD-1/PD-L1 inhibitors, alone or as part of a combination therapy, with respect to overall or progression-free survival among patients with mRCC. We developed a novel quantitative approach to synthesize subgroup findings across trials. The ratio of the subgroup-specific hazard ratios (HRs) from each study were pooled using a random effects meta-analysis whereby ratios of 1.00 would indicate that the subgroup-specific HRs were equal in magnitude. Results: From an initial 662 studies, five trials were judged to be eligible for inclusion. Meta-analyses suggested the treatment effect of PD-1/PD-L1 inhibitors in mRCC patients was modified by age (overall survival: ratio of HRage > 75 vs. HRage < 65= 1.51; 95% CI:1.01-2.26; I2= 0%, p= 0.04), PD-L1 expression (progression-free survival: ratio of HRPD-L1 > 10% vs. HRPD-L1 < 1%= 2.21; 95% CI:1.14-4.27; I2= 2.26%; p= 0.01), and sarcomatoid tumor presence (progression-free survival: HRno sarcomatoid differentiation vs. HRsarcomatoid differentiation= 1.54; 95% CI:1.07-2.21; I2= 0%; p= 0.02). Conclusions: Evidence suggests that older age, lower levels of PD-L1 expression, and absence of sarcomatoid tumour differentiation diminish the clinical efficacy of anti-PD-1/PD-L1 immunotherapies among mRCC patients.