Neoadjuvant Chemoimmunotherapy in Resectable Stage IIIA/IIIB Non-Small Cell Lung Cancer

Yulong Chen; Bo Yan; Feng Xu; Zhenzhen Hui; Gang Zhao; Jie Liu; Huan Zhang; Ziqing Zeng; Ran Zhang; Mariano Provencio; Xiubao Ren; Jian You

Disclosures

Transl Lung Cancer Res. 2021;10(5):2193-2204. 

In This Article

Abstract and Introduction

Abstract

Background: A small proportion of patients with non-small cell lung cancer (NSCLC) experience objective clinical benefit after neoadjuvant programmed cell death 1 (PD-1) blockade. A neoadjuvant therapeutic regimen combining immune checkpoint blockade with chemotherapy might improve the treatment effect, but such a regimen has not been tested in patients with resectable stage IIIA/IIIB NSCLC.

Methods: A retrospective study of 35 patients with resectable stage IIIA and IIIB NSCLC who were treated with neoadjuvant chemoimmunotherapy (NCIO) was performed. Patients were evaluated for pathological complete response (pCR), major pathologic response (MPR), safety, and feasibility. The correlations of pathologic response with various clinical factors were studied to identify predictors of pathological response.

Results: NCIO was associated with few immediate adverse events. NCIO did not delay planned surgery and led to a pCR rate of 51.43% and an MPR rate of 74.29% for the primary tumor. No association was observed between programmed death-ligand 1 (PD-L1) expression before NCIO and the pathologic response (Pearson's r=−0.071; P=0.685). However, a significant difference was observed in pathological response in patients with intracavitary and extracavitary tumors (P<0.05). Patients with intracavitary type had a higher pCR (76.47% vs. 31.58%) and MPR (100% vs. 50.00%) rate than patients with extracavitary type (Pearson's r=0.7280; P=0.0009).

Conclusions: NCIO was associated with few side effects, did not delay surgery, and achieved a pCR in 51.43% and MPR in 74.29% of resected tumors. No significant correlation was found between pathologic response and PD-L1 expression. While the intracavitary and extracavitary tumors type T was predictive of the pathological response to NCIO.

Introduction

The majority of the treatment methods have focused on the establishment of new treatment options for non-small cell lung cancer (NSCLC). Among various immunotherapies, programmed cell death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) have received the most attention so far.[1] Therapeutic blocking of the PD-1/PD-L1 axis using specific targeted monoclonal antibodies activates the immune system to recognize and target cancer cells via a T cell-mediated immune response.[2] Recently, neoadjuvant PD-1 blockade was also investigated in resectable NSCLC, but only a small percentage of patients obtained pathologic complete response (pCR). The clinical trial LCMC3 (ClinicalTrials.gov numbers: NCT02927301) reported that the MPR rate in the initial 82 patients was 18% with pCR rate of 4%.[3] Thus, the combination of checkpoint blockade and chemotherapy possesses the potential for synergistic immune activation. Several clinical studies have focused on neoadjuvant immunotherapy prior to tumor resection for advanced NSCLC. At the 2019 World Conference on Lung Cancer, it was reported that neoadjuvant anti-PD-1 immunotherapy did not delay surgery and achieved an MPR in 83% of patients who underwent tumor resection in a clinical study.[4] However, during the 2020 ASCO Annual Meeting, Zinner reported that only 6 (46%) and 5 (38%) patients out of a group of 13 patients with resectable NSCLC achieved MPR and pCR, respectively.[5] Recently, Shu reported on a phase II clinical trial of neoadjuvant atezolizumab and chemotherapy in patients with resectable NSCLC. Out of 30 patients, there were 17 (57%; 95% CI: 37–75%) cases of MPR and 10 (33%; 17–53%) cases of pCR.[6] And there are several case reports related the neoadjuvant immunotherapy prior to tumor resection for advanced NSCLC.[7,8] However, a systematic and in-depth discussion of this topic has yet to be reported in any journal, and a high-performance predictive factor, which would be critical and of tremendous assistance to avoiding non-essential surgery, still needs to be identified. Herein, we examined the safety and feasibility of the use of neoadjuvant PD-1 antibody plus chemotherapy in a small group of patients with resectable stage IIIA/IIIB NSCLC. In addition, the correlations of pathologic response with various clinical factors, including PD-L1 expression, CD4+ and CD8+ T cells, regulatory T cells (Tregs), and intracavitary or extracavitary type, were analyzed to identify predictors of pathological response. We present the following article in accordance with the STROBE reporting checklist (available at http://dx.doi.org/10.21037/tlcr-21-329).

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