Combination regimens including anti-PD-L1 therapies may improve some outcomes, when compared with sunitinib, in patients with metastatic renal cell carcinoma (RCC), according to a meta-analysis published in JAMA Network Open.

Patients with metastatic RCC who received anti-PD-L1 therapies had improved progression-free survival (PFS) but no improvement in overall response rate (ORR) or overall survival (OS), compared with patients who received sunitinib.

This meta-analysis included 3 trials. In 2 trials — IMmotion150 ( Identifier: NCT01984242) and IMmotion151 ( Identifier: NCT02420821) —­ researchers compared atezolizumab plus bevacizumab with sunitinib. In the JAVELIN Renal 101 trial (NCT02684006), researchers compared avelumab plus axitinib with sunitinib.

Pooled data showed no significant difference in OS between the patients who received anti-PD-L1 combinations and those who received sunitinib (hazard ratio [HR], 0.88; 95% CI, 0.75-1.03; P =.11).

Likewise, anti-PD-L1 agents did not significantly improve ORR compared with sunitinib (odds ratio [OR], 1.63; 95% CI, 0.79-3.35; P =.19). However, patients who received anti-PD-L1 agents had a significant improvement in PFS (HR, 0.78; 95% CI, 0.69-0.88; P <.001).

In patients with PD-L1 expression, anti-PD-L1 agents were associated with improved PFS (HR, 0.66; 95% CI, 0.56-0.79; P <.001) and ORR (OR, 2.28; 95% CI, 1.17-4.46; P =.02). However, there was no significant difference in OS between the anti-PD-L1 and sunitinib groups among patients with PD-L1 expression (HR, 0.84; 95% CI, 0.67-1.05; P =.12).

The researchers speculated that anti-PD-1 agents may be more effective than anti-PD-L1 agents in RCC.

“In other tumor subtypes, such as non-small cell lung cancer, evidence suggests that anti-PD-1 agents could be more effective than anti-PD-L1 agents, as anti-PD-1 agents simultaneously block PD-1 binding with both PD-L1 and PD-L2,” the researchers wrote. “However, anti-PD-L1 agents did not influence the PD-1/PD-L2 interaction, which may inhibit T-cell activation. Therefore, in the setting of anti-PD-L1 agent use, the PD-1 or PD-L2 could be used by the tumor to escape the antitumor immune response.”

The researchers noted, however, that additional research is needed to test this theory in RCC.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Maiorano BA, Ciardiello D, Maiello E, Roviallo G. Comparison of anti–programmed cell death ligand 1 therapy combinations vs sunitinib for metastatic renal cell carcinoma: A meta-analysis. JAMA Netw Open. Published online May 18, 2023. doi:10.1001/jamanetworkopen.2023.14144