Adjuvant immunotherapy in early-stage resectable non-small cell lung cancer: A new milestone

Abstract

Currently, chemotherapy is the standard adjuvant treatment for early-stage non-small cell lung cancer (NSCLC). However, adjuvant cisplatin-based chemotherapy after surgery has been shown to improve 5-year survival rates by only 4-5%. Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. Here, we summarize the rationale for adjuvant immunotherapy, including the postoperative immunosuppressive environment and immunological effects of platinum chemotherapy. Many ongoing clinical trials and the related progress in adjuvant immunotherapy in early-stage resectable NSCLC are discussed. Furthermore, we highlight several unresolved challenges, including markers predictive of treatment benefit, the efficacy of treatment for some oncogene-addicted tumors, the optimal combination therapy, the duration of adjuvant immunotherapy, and optimal selection between neoadjuvant and adjuvant immunotherapy. Early findings in some clinical trials are promising, and updated overall survival results will be useful for validating the current role of adjuvant immunotherapy, particularly in the context of perioperative strategy.

Keywords: adjuvant immunotherapy; chemotherapy; immune checkpoint inhibition; immune suppression environment; resectable non-small cell lung cancer.

Figure 1

Summary of mechanisms of postoperative immunosuppression and immunological effects of chemotherapy on the tumour microenvironment. CTLA-4, cytotoxic T-lymphocyte-associated protein 4; DCs, dendritic cells; IFN, interferon; IL, interleukin; MDSC, myeloid derived suppressor cells; NK cell, natural killer cell; PD-1, programmed cell death protein 1; STAT6, signal transducer and activator of transcription 6; TNF, tumor necrosis factor; Tregs, regulatory T cells.

Figure 2

Summary of ongoing adjuvant immunotherapy clinical trials. ALK, anaplastic lymphoma kinase; Chemo, chemotherapy; EGFR, epidermal growth factor receptor; ICI, immune checkpoint inhibitor.

Figure 3

Summary of survival rates of clinical trials. (A) 3-year disease-free survival rates and 5-year overall survival rates of patients with stage II-IIIA non–small cell lung cancer in the IMpower010 trial. (B) 3-year disease-free survival rates of patients with stage IB-IIIA non-small cell lung cancer in the IMpower010 and KEYNOTE-091 trials. ALK, anaplastic lymphoma kinase; Chemo, chemotherapy; DFS, disease-free survival; EGFR, epidermal growth factor receptor; OS, overall survival; PD-L1, programmed death-ligand 1.