PD-1 inhibition may result in better solid tumor survival than PD-L1 inhibition
medwireNews: Treatment with PD-1 inhibitors offers better overall survival (OS), with comparable tolerability, than does treatment with PD-L1 inhibitors for patients with solid tumors such as non-small-cell lung cancer (NSCLC), suggests a systematic review and meta-analysis.
Zhijie Wang (Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing) and colleagues analyzed data from 19 randomized clinical trials that evaluated the efficacy of PD-1 or PD-L1 inhibitors used as monotherapy or in combination with standard treatment in 11,379 patients with solid tumors.
They found that those treated with a PD-1 inhibitor had a significant 25% lower risk for death and a significant 27% lower risk for disease progression or death than those who received a PD-L1 inhibitor.
The researchers explain that previous studies comparing PD-1 and PD-L1 inhibitors have given discrepant results due to “insufficient comparability of the included studies and the lack of appropriate approach for indirect comparisons.”
In the current analysis, Wang and team used a mirror principle approach to minimize potential bias, where “studies of anti–PD-1 and anti–PD-L1 were screened and paired with mirrored trial characteristics, including tumor types, treatment lines, intervention regimens, control groups, and biomarker status, into individual mirror groups for further comparisons.”
This method resulted in seven mirror groups that were adjusted for indirect comparison. Among the trials included, 13 involved patients with NSCLC and two trials each comprised patients with gastroesophageal junction cancer, urothelial cancer, and renal cell carcinoma (RCC).
Anti-PD-1 treatments included nivolumab and pembrolizumab monotherapy (n=3 trials each) as well as pembrolizumab in combination with standard therapy (n=4), while the anti-PD-L1 trials included avelumab alone (n=2) or in combination with standard therapy (n=1) and atezolizumab monotherapy or combination therapy (n=3 each).
When the researchers looked at the individual tumor types, they found that OS was significantly longer with PD-1 than with PD-L1 inhibition for patients with NSCLC (hazard ratio [HR] for death = 0.77) and gastroesophageal junction cancer (HR=0.57), but the improvements in OS were non-significant for those with urothelial cancer and RCC.
However, the team stresses that the small number of studies among patients with gastroesophageal junction cancer, urothelial cancer, and RCC provides “insufficient power to draw reliable conclusions within these tumor types.”
Wang and co-investigators also looked that the safety profiles of the two treatments but found no significant differences between them in either adverse event (AE) rates overall or in immune-mediated AEs.
Writing in JAMA Oncology, the authors conclude: “The magnitude of possible survival benefit of anti–PD-1 compared with anti–PD-L1 is clinically relevant, which may provide important clues for treatment selection for clinicians in clinical practice.”
They add: “Future head-to-head studies are warranted for direct comparison across alternative interventions.”
By Laura Cowen
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