Comprehensive Demographics and Clinical Profile of NSCLC Patients: Analyzing Treatment Patterns With PD-L1 Stratification

Lung cancer is the most incident neoplasm in the world (considering both sexes), with 2.4 million (12.4%) new cases per year, based on estimates from the Global Cancer Observatory (Globocan) in 2022 (1). Non-small cell histology (NSCLC) is the most common and represents around 76% of lung cancer cases (2). Despite improvements in its prevention and diagnosis, a large proportion of patients are diagnosed in the advanced stage of the disease (57%) (3) and some of those diagnosed with localized disease will experience recurrence of the neoplasm. In this sense, choosing the most appropriate first-line treatment is necessary.

The last decade has been marked by advances in the treatment of lung cancer. Regarding metastatic non-small cell lung cancer without target mutation, the inclusion of immunotherapy in the therapeutic arsenal has led to a significant increase in survival rates (2). Currently, with the exception of a few patients given specific contraindications, an immunological check point inhibitor (ICI) will be present in the first-line treatment of this group (4). The current challenge is choosing the best treatment approach for each patient.

The use of ICI in the first line can be used as monotherapy or combination therapy. In 2016, the KEYNOTE-024 study was published in NEJM, a pioneer in this scenario, which evaluated the use of Pembrolizumab monotherapy in patients with a TPS score ≥50% (5). It was a positive study for its primary outcome of progression-free survival (PFS), with a median PFS of 10.3 months for the group that received Immunotherapy versus 6.7 months for the group that received chemotherapy (CT) (HR 0.5; 0.37 - 0.68 ). It also demonstrated a significant gain in overall survival (OS), with 5-year follow-up reaffirmation - median OS 26.3 months for Pembrolizumab versus 13.4 months for CT (HR 0.62; 0.48 - 0.81) (6). Five years after first publication of KN-024, the EMPOWER Lung-01 study was published in the Lancet (7). He evaluated the use of Cemiplimab in the same population and also obtained positive results in relation to OS (26.1 months ICI arm versus 13.3 months in the CT arm - HR 0.57; 0.46 - 0.71) (8) and PFS.

In relation to patients with low expression (1-49%) or without PD-L1 expression (negative), the combination of immunotherapy and chemotherapy appears to be a good treatment strategy. The KEYNOTE-189 study, published in NEJM in 2018, evaluated the use of Pembrolizumab associated with doublet chemotherapy (Carboplatin or Cisplatin + Pemetrexed) in patients with lung adenocarcinoma without target alteration (EGFR or ALK) regardless of PD-L1 expression (9). Their results show a survival benefit with the use of the combination with ICI and updated data on 5-year OS maintain this gain (19.4% versus 11.3%) (10). In the same year, the KEYNOTE-407 study evaluated the use of Pembrolizumab in combination with CT in patients with squamous histology. Similarly, it demonstrated a survival benefit (11). In its most recent update, the 5-year OS data maintains benefit for the ICI combination arm, with a 29% reduction in the risk of death (12).

In this same subgroup, other medications were evaluated. The IMPOWER-150 study evaluated the use of Atezolizumab in combination with CT, with and without the VEFG inhibitor (Bevacizumab) (13). It included patients with metastatic lung adenocarcinoma and included patients with EGFR and ALK mutations, but only in a small proportion. The study met its coprimary endpoints of PFS and OS, with a median OS of 19.0 months for the ICI+CT+Bevacizumab combination versus 14.7 months for the CT+Bevacizumab arm (14).