Understanding the treatment effect modification of mono- or combination PD-1/PD-L1 inhibitor therapies on survival outcomes in patients with metastatic renal cell carcinoma: What does the literature say?

Abstract

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.