Integrating immune checkpoint inhibitors and targeted therapies in the treatment of early stage non-small cell lung cancer: a narrative review

Abstract

Prognosis of early stage non-small cell lung cancer (eNSCLC) is poor even when treated radically with surgery and (neo)adjuvant chemotherapy (Cht). The discovery of tyrosine kinase inhibitors (TKIs) for oncogene addicted NSCLC and immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic paradigm and improved survival of advanced NSCLC. The unprecedented impact of these drugs has shifted the focus of investigation to early stage disease aiming at improving cure. In this context, several single arm phase II studies evaluating neoadjuvant ICI alone or in combination with platinum-based Cht have shown encouraging rates of pathological response which have spurred several ongoing randomized trials with (neo)adjuvant ICI. More recently, ADAURA study evaluating adjuvant osimertinib demonstrated a profound reduction of the risk of recurrence in patients with stage I (>4 cm)-IIIA eNSCLC harbouring EGFR sensitizing mutations. ICIs and TKIs represent a true revolution in the treatment of eNSCLC call to challenge the current standard of care. However, questions regarding drug resistance, recurrence patterns, biomarker identification, optimal treatment duration and sequencing need be answered to effectively integrate new drugs in the rapidly evolving therapeutic landscape of NSCLC. In this review we critically review new developments and future perspectives of TKIs and ICI as (neo)adjuvant strategies for eNSCLC.

Identification of a Ferroptosis-Related LncRNA Signature as a Novel Prognosis Model for Lung Adenocarcinoma

“…LUAD is characterized by a high degree of heterogeneity, and studies have demonstrated that a variety of genetic mutations and epigenetic changes drive the development and progression of LUAD, including gene fusion, major chromosomal events, single nucleotide changes (SNVs) and copy number alterations (CNAs) (36,37). In recent years, with the in-depth understanding of the changes in the molecular mechanism of LUAD, many molecular targeted drugs for the precise treatment of LUAD have been developed, such as tyrosine kinase inhibitors (TLIs) of epidermal growth factor receptor (EGFR) and PDL1/PDL inhibitors (38,39), which bring hope to LUAD patients. However, these mutations are not ubiquitous in all LUAD patients, and existing targeted drugs are only effective in some patients, and even some patients develop resistance and relapse during treatment.…”

WITHDRAWN: Stromal Cell-Derived Factor 1 Secreted by Cancer- Associated Fibroblasts Promotes lncRNA Xist through CXCR4 and Facilitates Invasion and Metastasis of Non-Small Cell Lung Cancer

“…The most common histology is non-small cell lung cancers (NSCLC), which accounts for nearly 85% of cases [2], and the vast majority of NSCLC patients are found in in the stage of advanced inoperable [3] since early stage tumor development is usually asymptomatic [4]. The prognosis of early NSCLC is poor even if it is treated by surgery and neoadjuvant chemotherapy [5]. Up to 70% of NSCLC patients develop central nervous system metastases during the course of their disease [6].…”

EGFR Status Assessment for Better Care of Early Stage Non-Small Cell Lung Carcinoma: What Is Changing in the Daily Practice of Pathologists?

“…Different clinical trials have been performed with the aim to evaluate the efficacy of TKIs targeting activating mutations in EGFR in the neoadjuvant and also in the adjuvant setting [18][19][20]. Briefly, these trials have used or use inhibitors of the first, second, and third TKI generation [19,21].…”