Abstract
Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized.
Highlights
The global incidence of lung cancer has prominently increased among the various cancers in the last three decades
Lung cancer has become the leading cause of cancerrelated deaths in both males and females [1,2]. It is histologically classified as non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC); NSCLC accounts for 85% of cases [3,4]
Surgery remains the main treatment for early-stage NSCLC, and approximately 30% of NSCLC patients present with the surgically resectable disease at initial diagnosis [5]; the risk of disease recurrence and cancer-related mortality are high, even for those NSCLC patients receiving complete resection [5,6]
Summary
The global incidence of lung cancer has prominently increased among the various cancers in the last three decades. In currently ongoing four main phase III clinical trials (KEYNOTE 617, CheckMate 816, IMpower 030, AE-GEAN) with neoadjuvant chemotherapy plus ICIs or placebo, post-operative consolidation ICIs therapy is administrated in the treatment group patients [78,98,99,100]. These four clinical trials will provide clear evidence on the efficacy of ICIs administrated before and after surgery in early-stage and resectable NSCLC. The second U.S FDA-approved and first oncolytic virus vaccine was talimogene laherparepvec (T-VEC) (Imlygic®), which has been indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery, and which has demonstrated a significantly durable response rate [110,111,112]
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