Anti-PD-1 Therapy May Induce Better Survival Outcomes Compared With Anti-PD-L1

Findings from a recent study supported further evaluation of comparing anti–PD-1 to anti–PD-L1 therapy to help determine treatment options for patients with cancer.

Anti—PD-1 therapy demonstrated improved survival outcomes, compared with anti–PD-L1 treatment in patients with solid tumors, according to study findings published in JAMA Oncology.

This finding was consistent when comparing these agents as monotherapies or in combination regimens.

“Immunotherapy is one of the most important breakthroughs in cancer treatment, especially immune check-point inhibitors targeting programmed cell death 1 (PD-1) and PD ligand 1 (PD-L1), which significantly prolonged overall survival and possessed superior safety profile in patients with cancer compared with standard therapies across a wide range of tumor types, the researchers explained. “With the increasing studies in immunotherapy, differences between the clinical performance of anti—PD-1 and anti–PD-L1 started to be reported.”

However, there are discrepancies among findings of studies that have evaluated these two types of treatments. Making it difficult to understand the similarities and differences between anti—PD-1 and anti–PD-L1 for the ultimate benefit of patients with cancer.

Therefore, the researchers aimed to assess differences in efficacy and safety data from 19 randomized clinical trials across multiple tumor types. In total, 11,379 patients were included in the meta-analysis.

The researchers noted that the 19 trials were selected based on the “mirror principle” to ensure the comparability of the included studies and avoid the risk of bias in this meta-analysis. “The mirror principle used in our present study may provide a valuable tool for the indirect comparative analysis with a minimal risk of bias across multiple interventions,” they explained.

Overall, anti—PD-1 therapy exhibited superior overall and progression-free survival (the time from treatment to disease progression or worsening) compared with anti–PD-L1 therapy. The researchers found no significant difference in their safety profiles.

“The possible survival superiority seems even stronger when anti—PD-1 was used in combination with standard therapies, which lowered the risk of death by 32% compared with anti–PD-L1 plus standard therapies as evidenced in the results of (non-small cell lung cancer) and (renal cell carcinoma) trials,” the researchers explained, adding that T-cell activation might be inhibited by PD-L1 antibody overconsumption owing to extra PD-L1 expression, which needs to be explored in future studies.

In addition, their sensitivity analysis presented consistency in the overall estimates across these analyses.

“Anti—programmed cell death 1 appears to exhibit favorable survival outcomes and a comparable safety profile with anti–programmed cell death ligand 1 in cancer therapy, which may provide valuable insight for future treatment strategy,” the researchers wrote.

They added that these findings could help to provide more insight into which treatments should be used in certain patients with cancer.

“Future head-to-head studies are warranted for direct comparison across alternative interventions,” they concluded.