The Evolving Role of Immunotherapy in Stage III Non-Small Cell Lung Cancer.

Parneet K. Cheema,Kirstin Perdrizet

doi:10.3390/curroncol28060451

Parneet K. Cheema, Kirstin Perdrizet

Open Access

https://doi.org/10.3390/curroncol28060451

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Abstract

The management of Stage III non-small cell lung cancer (NSCLC) is complex and requires multidisciplinary input. Since the publication of the PACIFIC trial (consolidative durvalumab post concurrent chemotherapy and radiation in Stage III disease) which showed improved survival for patients in the immunotherapy arm, there has been much interest in the use of immunotherapy in the Stage III setting. In this review, we explore the biologic and clinical rationale for the use of immunotherapy in Stage III NSCLC, present previously published and upcoming data in the neoadjuvant, adjuvant, and concurrent realms of Stage III management, and discuss unanswered questions and challenges moving forward.

Highlights

20–30% of patients diagnosed with non-small cell lung cancer (NSCLC)present with Stage III disease [1]
Mechanisms that can increase the immune response, such as Immune check point inhibitors (ICIs), as well as the gains in overall survival (OS) realized with ICIs in the metastatic setting, have led to multiple trials in the adjuvant setting investigating whether improved cure rates can be achieved
EGFR positive patients were included in IMpower010, given the results of the ADAURA study and questionable benefit of ICIs in later line treatment of EGFR positive NSCLC, it is likely that most clinicians will opt for adjuvant osimertinib in these patients

Summary

Introduction

20–30% of patients diagnosed with non-small cell lung cancer (NSCLC). present with Stage III disease [1]. Adjuvant data from the IMpower revealed the PD-L1 inhibitor atezolizumab improved disease-free survival (DFS) following resection of PD-L1 positive Stage II and III NSCLC, and has supported expanding role of ICIs in the adjuvant setting [7]. Given these recent advances and little change in the adjuvant treatment landscape for NSCLC since the widespread use of adjuvant platinum doublet chemotherapy, trials of ICIs in the surgical (neoadjuvant and adjuvant) and non-surgical (concurrently or following completion of cCRT) have been initiated. III NSCLC setting, review treatment implications for patients, and discuss challenges and unanswered questions moving forward

Adjuvant

Adjuvant ICIs

Challenges and Unanswered Questions

Neoadjuvant

Neoadjuvant ICI Monotherapy

Neoadjuvant Combination ICIs

Neoadjuvant ICIs with Chemotherapy

ICIs with cCRT

Findings

Conclusions