A narrative review of primary research endpoints of neoadjuvant therapy for lung cancer: past, present and future

Abstract

Objective: This review summarizes the current status of neoadjuvant therapy and discusses the choice of new clinical research endpoints for non-small cell lung cancer.Background: Neoadjuvant chemotherapy is a recognized practice in patients with resectable and locally advanced lung cancer. With the introduction of molecular targeted drugs and immune checkpoint inhibitors (ICIs), the overall survival (OS) of patients with lung cancer has been significantly improved, and the original traditional clinical research endpoints are no longer suitable for existing clinical research. In order to accelerate the process of clinical trials and the development and approval of drugs, it is necessary to find suitable alternative indicators as the main indicators of clinical research.Methods: Therefore, this article focuses on clinical trials using disease-free survival (DFS), progression free survival, and pathological evaluation indicators, pathologic complete response and major pathologic response, as surrogate endpoints. We search related literature through PubMed database and clinical trials through clinicaltrials.gov.Conclusions: Pathologic complete response and major pathologic response are recommended as surrogate endpoints in the era of neoadjuvant immunotherapy, and secondary endpoints are listed for the prediction of pathological results. In addition, the definitions of major pathological response (MPR) and PCR should be standardized, and a new pathological evaluation standard should be developed, which is applicable to all current treatment methods.

Multimodality Treatment including Surgery Related to the Type of N2 Involvement in Locally Advanced Non-Small Cell Lung Cancer

“…Both MPR and pCR have now been generally accepted as surrogate endpoints for survival in neoadjuvant immunotherapy for resectable NSCLC. However, they have not yet been validated and therefore, further studies are needed [ 28 , 29 , 30 , 31 , 32 , 33 ].…”

Sintilimab for the treatment of non-small cell lung cancer

“…Alternatively, pathologic response evaluation after neoadjuvant therapy provides a window to assess the anti-tumor efficacy and possible clinical benefits achieved in patients at an early time point [ 66 ]. MPR is defined as 10% or less residual viable tumour after neoadjuvant chemotherapy, and pCR is defined as the absence of any remaining active tumor cells [ 67 ]. Both MPR and pCR are recommended as surrogate endpoints for lung cancer in the era of neoadjuvant immunotherapy [ 67 ].…”

“…MPR is defined as 10% or less residual viable tumour after neoadjuvant chemotherapy, and pCR is defined as the absence of any remaining active tumor cells [ 67 ]. Both MPR and pCR are recommended as surrogate endpoints for lung cancer in the era of neoadjuvant immunotherapy [ 67 ].…”

Pathological Response and Immune Biomarker Assessment in Non-Small-Cell Lung Carcinoma Receiving Neoadjuvant Immune Checkpoint Inhibitors

“…In patients with NSCLC treated with neoadjuvant chemotherapy, tumors with a PR value of 10% or less are considered to have achieved MPR, and tumors with an absence of viable tumor cells are considered to have a pCR [ 28 ]. MPR has been associated with long-term overall survival (OS) in retrospective studies of several clinical trials of neoadjuvant chemotherapy [ 17 , 29 , 30 , 31 ].…”

“…The pathological features of NSCLC tumor samples from patients treated with neoadjuvant chemotherapy have been studied by several investigators [ 17 , 29 , 30 , 31 ]. A detailed outline of recommendations from The International Association for the Study of Lung Cancer (IASLC) has been released to standardize assessment and allow for comparison among new therapeutic options that are tested in clinical trials, such as tyrosine kinase inhibitors or immunotherapy with ICIs [ 28 ].…”