2016YFC0905500, 2016YFC0905503). Authors contributions YZ and LZ concept and design this study. ?1%, TPS 1 to 49% and TPS 50%. IMpower131: PD-L1 expression was evaluated using the VENTANA SP142 IHC assay. TC3 or IC3 (high)?=?TC??50% or IC??10% PD-L1+; TC1/2 or IC1/2 (low)?=?TC??1% and? ?50% or IC??1% and? ?10% PD-L1+; TC0 and IC0 (negative)?=?TC and Rifaximin (Xifaxan) IC? ?1% PD-L1+. IC, tumor-infiltrating immune cell; TC, tumor cell Open in a separate window Fig. 1 Diagram of the indirect comparison between pembrolizumab plus chemotherapy vs. atezolizumab plus chemotherapy for advanced squamous non-small-cell lung cancer. Solid lines between treatment regimens represented the existence of direct comparisons. confidence interval, Hazard ratio, Rifaximin (Xifaxan) Risk ratio, overall survival, progression-free survival, objective response rate, adverse event, programmed death ligand 1.?A statistical test with em P /em -value??0.05 was considered as significant In IMpower131, PD-L1 expression was scored by immunohistochemistry (SP142 assay) in tumor cells (as percentage of PD-L1-expressing tumor cells 50%, TC3; 5% and? ?50%, TC2; 1% and? ?5%, TC1 and? ?1%, TC0) and tumor-infi ltrating immune cells (as percentage of tumor area:10%, IC3; 5% and? ?10%, IC2; 1% and? ?5%, IC1; and? ?1%, IC0). In KEYNOTE-407, PD-L1 expression was scored by immunohistochemistry (22C3 assay) in tumor cells (as percentage of PD-L1-expressing tumor cells TPS 50%, 1% and? 50%, and? ?1%) aHR is used for OS and PFS evaluation, RR is used for ORR and AE evaluation bPD-L1 High is defined as TC3 or Rifaximin (Xifaxan) IC3 in IMpower131, TPS 50% in KEYNOTE-407 cPD-L1 Low is defined as TC1/2 or IC1/2 in IMpower131, TPS 1% and? ?50% in KEYNOTE-407 dPD-L1 Negative is defined as TC0 and IC0 in IMpower131, TPS ?1% in KEYNOTE-407 Discussion According to this indirect comparison, we found pembrolizumab plus chemotherapy seemed to be superior in terms of OS and PFS compared to atezolizumab plus chemotherapy, most notable in PD-L1 low/negative subgroup of patients. Not surprisingly, both of pembrolizumab and atezolizumab showed similar efficacy in PD-L1 high patients. Theoretically, PD-1 antibody can bind to PD-1 protein on T cells, so it will block the binding of PD-1 to PD-L1 and PD-L2 at the same time, while PD-L1 antibody can only interact with PD-L1, so it will only block the binding of PD-1 to PD-L1. Therefore, T cells might still be inhibited by the interaction between PD-1 and PD-L2 using anti-PD-L1 treatment . For PD-L1 high patients, Anti-PD-L1 and Anti-PD-1 treatment might be effective similarly, because PD-L1 expression might be dominant for those patients. However, for PD-L1 low/negative patients, the expression spectrum of immunological molecule might be complicated, such as PD-L2 expression enhancement. As a result, Anti-PD-L1 treatment might not be enough compared with Anti-PD-1 treatment for PD-L1 low/negative patients. The major limitation of this study was the limited follow-up time for KEYNOTE-407 and IMpower131, so that we used relative variables (HR and RR) instead of absolute value Rifaximin (Xifaxan) (median survival time) for analyses to lower the bias. Besides, the proportion of PD-L1 high patients was slightly higher in KEYNOTE-407, while the proportion of PD-L1 negative patients was slightly higher in IMpower131, both in experimental group and control group. It might cause imbalance of the patient population which affected the comparability of this indirect comparison. Moreover, PD-L1 expression was scored by SP142 assay in IMpower131, while it was scored by 22C3 assay in KEYNOTE-407, thus might have influence on PD-L1 level evaluation. Recent studies demonstrated the percentage of PD-L1-stained tumor cells was highly comparable among 22C3, 28C8 and SP263 PD-L1 assays, while SP142 assay exhibited fewer stained tumor cells, [8, 9] which was in accordance with the proportion of PD-L1 level population in KEYNOTE-407 (higher PD-L1 high patients) and Rifaximin (Xifaxan) IMpower131 (higher PD-L1 detrimental sufferers). Somewhat, it proved that the entire individual people between IMpower131 and KEYNOTE-407 was comparable. Nonetheless it should be careful to interpret the subgroup evaluation stratified by PD-L1 level. In the end, our research was an indirect evaluation analysis, which can compromise the data level. Conclusions These restrictions aside, our research firstly likened pembrolizumab plus chemotherapy and atezolizumab plus chemotherapy for advanced squamous NSCLC and discovered the former appeared to be excellent with regards to Operating-system and PFS compared to the latter, in PD-L1 low/detrimental sufferers specifically. Our analysis offers a hint that anti-PD-1 antibody may have excellent efficacy in comparison to anti-PD-L1 antibody in conjunction with chemotherapy for sufferers with PD-L1 low/detrimental advanced squamous NSCLC. Extra research are warranted to verify this. Financing This function was supported with the Country wide Key R&D Plan of China (Offer No. 2016YFC0905500, 2016YFC0905503). Authors efforts YZ and LZ idea and Rabbit polyclonal to ARFIP2 style this scholarly research. HZ and YZ produce the info and statistical.