Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis.

Abdulhakim A A Abunasser,Ehab J A Balawi,Jinmin Xue,Yuxi Zhu,Yuan Seng Wu

doi:10.1155/2021/6662344

Abdulhakim A A Abunasser, Ehab J A Balawi + Show 3 more

Open Access

https://doi.org/10.1155/2021/6662344

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Abstract

The morbidity and mortality of lung cancer remain one of the highest among multiple cancers, respectively. Small-Cell Lung Cancer (SCLC) accounts for around 10%–15% of all lung cancers. Approximately two-thirds of the diagnosed SCLCs are in extensive stage (ES). Decades later, we still rely on the same traditional regimen with etoposide and platinum (EP) as the mainstay of treatment with poor prognosis. This meta-analysis aims to assess the effect of adding Immune Checkpoint Inhibitors (CPIs) such as (ipilimumab, atezolizumab, pembrolizumab, and durvalumab) to the traditional EP regimen for small-cell lung cancer extensive stage (ES-SCLC). We searched through PubMed looking for studies that compare between EP and CPIs, with EP alone, and only Phase III randomized controlled trials were considered eligible for this study. A total of 3645 papers were the results of the initial search, and only 4 studies met our criteria. Each investigator extracted the data independently using the PRISMA MODEL (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Each author used a prespecified sheet. The primary endpoint was to calculate OS (overall survival) and PFS (progression-free survival) hazard ratios for both arms. We found that adding EP plus CPIs increased both OS (HR, 95% CI 0.80 [0.70, 0.93], P = 0.0001, I2 = 49%) and PFS (HR95% CI 0.81 [0.74, 0.88], P < 0.00001, I2 = 0%). On the other hand, ORR (overall response rate) was not affected by the addition of CPIs to EP compared to EP alone, and the same was true for adverse events. To conclude, CTLA-4 alone is not encouraging, but PD-1/PD-L1 adds survival benefits. A combined treatment regimen shows to be more effective, improving overall survival rate Durvalumab and atezolizumab showed improvement for OS, but pembrolizumab and ipilimumab did not show a significant increase of OS over EP; however, pembrolizumab showed significant prolongation of the disease-free period.

Highlights

Lung cancer is the most diagnosed cancer and the most common cause of death among all types of cancers. It mainly consists of two categories: Small-Cell Lung Cancer (SCLC), which accounts for almost 10%–15% and Non-Small-Cell Lung Cancers (NSCLCs), which account for 85% of all lung cancers [1]
In 2016, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody combined with chemotherapy tested on SCLC showed no significant effects [11]
As for Eastern Cooperative Oncology Group (ECOG) status, the hazard ratio of ECOG0 was 0.94 (IV, fixed, 95% confidence intervals (CIs) 0.94 [0.78, 1.13], P 0.39, I2 69%), and the sensitivity test showed that the Martin Reck 2016 study had high weight over the result

Summary

Introduction

Lung cancer is the most diagnosed cancer and the most common cause of death among all types of cancers. In 2016, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody (ipilimumab) combined with chemotherapy tested on SCLC showed no significant effects [11]. We extracted the following items for each included trial: authors, study design, year of publication, place of publication, age, gender, smoking status, Eastern Cooperative Oncology Group (ECOG) Performance Status, PD-L1 level, lung cancer subtypes, metastasis, drugs, the hazard ratio of OS, PFS, ORR, and adverse events (AEs) for both arms, any other clinical outcomes, and the follow-up period.

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