Page 177 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology PD-1/L1 inhibitors in advanced CC: Multicenter retro

1. Introduction concurrent radiotherapy and chemotherapy. Notably,
the trial enrolled high-risk patients according to the
Cervical cancer is one of the main causes of cancer-related International Federation of Gynecology and Obstetrics
mortality for women worldwide and has seen a recent (FIGO) 2014 staging system, specifically those with
substantial increase, particularly in China. Cervical stages III–IVA disease, regardless of lymph node status,
1
cancer emerged as the most common gynecological cancer and patients with lymph node metastasis in stages IB2-
and the fourth most common cancer among women in IIB. Another highlight of the study is that compared with
2022, with approximately 661,021 new cases and 348,189 previous large clinical studies in Western countries, the
deaths. In developed nations, the implementation of proportion of Asian populations in the KEYNOTE-A18
2
human papillomavirus (HPV) vaccination, screening study was close to 30%. Chinese patients comprised 50% of
programs, and timely intervention for precancerous lesions Asian patients in the study, a proportion that significantly
has led to a substantial decline in late-stage morbidity and enhances the value of therapeutic guidance for Chinese
disease-specific mortality. Conversely, a disproportionate patients. Moreover, the results of the KEYNOTE-A18 trial
80% of global cervical cancer fatalities are concentrated revealed, for the 1 time, that the use of pembrolizumab
st
in low- and middle-income countries, primarily due to + simultaneous radiotherapy in the first-line treatment
insufficient screening initiatives and delayed diagnostic regimen resulted in significant improvement in PFS and
processes. Epidemiological data indicate that the Asian OS in locally advanced cervical cancer, with 36-month
3-5
region accounts for 58.3% of the global incidence of new PFS and OS rates, reaching 69.3% and 82.6%, respectively.
cases, with China contributing 17% of the mortality rate. These rates were higher than those in the placebo group,
6
These statistics underscore significant deficiencies in indicating that the integration of ICIs into the conventional
early detection and therapeutic interventions. Advanced treatment protocol for locally advanced cervical cancer is
cervical cancer, which is characterized by large tumors justified. Based on the results of that study, the National
18
and local and distant metastasis, is typically managed Comprehensive Cancer Network (NCCN) guideline added
with chemoradiation. The standard first-line therapeutic pembrolizumab + cisplatin/carboplatin as the preferred
approach for advanced cervical cancer currently involves regimen for the treatment of cervical cancer patients
platinum-based chemotherapy in conjunction with with FIGO 2014 stages III–IVA. This update implies
19
bevacizumab. Nevertheless, the majority of patients with the establishment of immune combination therapy as
advanced disease experience recurrence following first-line the standard of care for advanced cervical cancer. While
treatment. For advanced disease, the 5-year progression- randomized controlled trials are designed to maximize
7
free survival (PFS) and overall survival (OS) rates for internal validity through the implementation of rigorous
patients are only 50 – 70%. Stage IV patients exhibit a inclusion and exclusion criteria, the highly regulated
8
5-year OS rate of under 20%, underscoring the need for environment may inadvertently compromise external
9
novel therapeutic agents and modalities. validity. This can result in a study population that does
In 2018, the United States Food and Drug not fully capture the heterogeneity observed in real-
Administration approved pembrolizumab for the world clinical settings, including variations in racial and
treatment of programmed death-ligand 1 (PD-L1)- geographic distributions. To address this limitation and
to assess the generalizability of the KEYNOTE-A18 trial
positive recurrent metastatic cervical cancer based on the findings within the context of routine clinical practice,
results from the KEYNOTE-158 study, which proves that we initiated a multicenter retrospective cohort study. This
the application of immunotherapy in advanced cervical study, which included a substantial cohort of Chinese
cancer is feasible. In recent years, several clinical trials patients diagnosed with advanced cervical cancer (n=192),
10
have provided evidence that immunotherapy is a crucial systematically evaluated the efficacy and identified the
component of the treatments for cervical cancer, 11-15 and determinants of response to PD-1/PD-L1 inhibitors in a
it has emerged as a transformative strategy for advanced real-world setting. The primary objective was to generate
cancers. Programmed cell death protein 1 (PD-1)/PD-L1 evidence that more closely reflects the complexities and
inhibitors, the most widely used immune checkpoint nuances of clinical practice scenarios.
inhibitors (ICIs), attack cancer cells by reactivating and
inducing the proliferation of antigen-stimulated T cells 2. Materials and methods
in the tumor microenvironment. 16,17 The KEYNOTE-A18
study was a prospective, international, multicenter, 2.1. Participants and study design
randomized, controlled, phase III trial targeting locally From January 2020 to June 2023, clinical data of cervical
advanced cervical cancer. This study investigated cancer patients with FIGO 2018 stages IIIC and IV who
the potential of immunotherapy in conjunction with were diagnosed and treated in the First Affiliated Hospital

Volume 9 Issue 2 (2025) 169 doi:10.36922/ejmo.8074