Better Survival, Safety Profile With PD-1 Than PD-L1 Inhibitors

By Wil Boggs MD

December 30, 2019

NEW YORK (Reuters Health) - Survival outcomes and safety profiles appear to be better with PD-1 inhibitors than with PD-L1 inhibitors, according to a systematic review and meta-analysis.

"Our study indicated that PD-1 inhibitors might be a preferred choice when both PD-1 and PD-L1 inhibitors are approved for the same (indication)," said Dr. Jie Wang of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing, China.

"However, given the nature of indirect comparison in this meta-analysis, our findings could only serve as references for physicians rather than determining the treatment decisions directly," she told Reuters Health by email.

Immune-checkpoint inhibitors targeting PD-1 and PD-L1 have significantly prolonged overall survival with favorable safety profiles compared with standard therapies across a wide range of tumor types. The lack of head-to-head comparisons complicates the choice between these therapies, however.

For the study, published in JAMA Oncology, Dr. Wang and colleagues used adjusted indirect comparisons based on a mirror principle (to minimize potential bias) to assess differences between anti-PD-1 and anti-PD-L1. They included data from 19 randomized clinical trials involving more than 11,000 patients with non-small-cell lung cancer (NSCLC), gastric or gastroesophageal junction cancer (GC), urothelial cancer (UC), or renal cell carcinoma (RCC).

Patients treated with anti-PD-1 had significantly better overall survival than did patients treated with anti-PD-L1 (hazard ratio, 0.75). Results were consistent with monotherapy (HR, 0.78) and with combination therapy (HR, 0.68).

In analyses by tumor types, overall survival was significantly prolonged for patients treated with anti-PD-1 versus anti-PD-L1 in NSCLC and GC, but not in UC or RCC.

Results were similar when progression-free survival replaced overall survival as endpoint.

The overall safety profiles of anti-PD-1 and anti-PD-L1 were comparable for both any adverse event and immune-related adverse events, as well as for adverse events leading to death or study discontinuation.

"Intrinsic differences may present between PD-1 and PD-L1 inhibitors," Dr. Wang said. "Future head-to-head randomized controlled trials, if possible, are warranted for further investigations."

"With an increasing number of trials with immune-based combination therapies, this finding may provide clues for future designs and selections of treatment strategies," she said.

Dr. Ashish Ranjan of Oklahoma State University, in Stillwater, who recently reviewed cancer immunotherapy, told Reuters Health by email, "I think the data demonstrating anti-PD-1 effects against wild-type NSCLC is compelling and can be a good guidance to oncologists for incorporation of this agent in biopsy-confirmed personalized treatment regimens."

"Overall, anti-PD-1s in monotherapy and in combination chemotherapy appear to be more effective against certain tumor types than anti-PD-L1s," said Dr. Ranjan, who was not involved in the study. "Additional studies are still needed to verify the outcomes in melanoma, GC, and other tumor types for wide-range adoption of this drug (class) in oncologic settings."

SOURCE: JAMA Oncology, online December 26, 2019.