Analysis of response rate with ANTI PD1/PD-L1 monoclonal antibodies in advanced solid tumors: a meta-analysis of randomized clinical trials

Alberto Carretero-González, David Lora, Ismael Ghanem, Jon Zugazagoitia, Daniel Castellano, Juan Manuel Sepúlveda, José Antonio López-Martin, Luis Paz-Ares, Guillermo de Velasco _

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Oncotarget. 2018; 9:8706-8715. https://doi.org/10.18632/oncotarget.24283

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Alberto Carretero-González1, David Lora2, Ismael Ghanem3, Jon Zugazagoitia1, Daniel Castellano1, Juan M. Sepúlveda1, José A. López-Martin1, Luis Paz-Ares1 and Guillermo de Velasco1

1Medical Oncology Service, University Hospital 12 de Octubre, Madrid, Spain

2Clinical Research Unit (imas12-CIBERESP), University Hospital 12 de Octubre, Madrid, Spain

3Medical Oncology Service, University Hospital La Paz, Madrid, Spain

Correspondence to:

Guillermo de Velasco, email: gdvelasco.gdv@gmail.com

Keywords: AntiPD1/PDL1; nivolumab; pembrolizumab; atezolizumab; response rate

Received: September 11, 2017     Accepted: January 13, 2018     Published: January 20, 2018


Background: Anti-PD1/PD-L1 monoclonal antibodies (mAbs) increase overall survival compared to standard of care (SOC) in different tumors. However, a proportion of patients (pts) will have progressive disease (PD) as best response. We conducted a meta-analysis to study the rates of response comparing these antibodies with SOC.

Methods: A search of published trials in MEDLINE and EMBASE analyzing anti-PD1/PD-L1mAbs monotherapy compared to SOC. Relative risk (RR) with 95% confidence interval (CI) of response rates between groups was estimated. Subgroup analyses for location of primary tumor, number of previous treatment lines, selected population by PD-L1 expression and type of radiological assessment were made.

Results: Twelve studies accounting for 6,700 pts were included (anti-PD1/PD-L1 mAbs: 3,451 pts; SOC: 3,249 pts [2,823 pts: chemotherapy, 426 pts: targeted therapy]). Adjusted response rates were (N, %): Complete Response (CR) (69/3153, 2.19%), Partial Response (PR) (596/3153, 18.90%), Stable Disease (SD) (632/2463, 25.66%) and PD (1027/2463, 41.70%); and CR (16/2955, 0.54%), PR (263/2955, 8.90%), SD (835/2269, 36.80%) and PD (834/2269, 36.76%) with anti-PD1/PD-L1 mAbs and SOC, respectively. Anti-PD1/PD-L1 mAbs improved CR rate (RR 3.48) and PR rate (RR 2.27). There were no differences in the PD rate between groups (RR 1.10). Subgroup analyses showed an improvement in clinical benefit with anti-PD1/PD-L1 mAbs for melanoma (RR 1.59; 1.37–1.84 95% CI) and those treated in the first line setting (RR 1.57; 1.27–1.95 95% CI).

Conclusions: Anti-PD1/PD-L1 mAbs increase overall response rate compared to SOC without an increase in PD rate. Melanoma and pts treated in first line setting seem to have greater benefit with anti-PD1/PD-L1 mAbs.

Findings: In this systematic meta-analysis, anti-PD1/PD-L1 mAbs were associated with a greater overall response rate. Patients with melanoma and those managed in the first line setting seem to have an additional benefit with anti-PD1/PD-L1 mAbs.

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