Real-world clinical outcomes of neoadjuvant immunotherapy combined with chemotherapy in resectable non-small cell lung cancer

Wu, Junqi; Hou, Likun; E, Haoran; Zhao, Yue; Yu, Xin; Xu, Long; Ye, Ning; Deng, Jiajun; Sun, Ke; Zhang, Jie; Wu, Chunyan; Zhu, Yuming; Zhao, Deping; She, Yunlang; Su, Chunxia; Chen, Chang

doi:10.1016/j.lungcan.2022.01.019

Cited by 24 publications

(17 citation statements)

References 39 publications

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“…After PSM, the MPR rate of the PD‐1 + Chemo group was 48.4%, which was significantly higher than that of the Chemo group (17.2%). In accordance with previous reports, 6,7,15–24 MPR rates ranged from 27% to 86% in the chemoimmunotherapy modality, while the range was 8.9% to 16% with neoadjuvant chemotherapy alone. Several studies 16,22 have reported relatively higher MPR rates in squamous cell carcinoma patients.…”

Section: Discussionsupporting

confidence: 92%

“…However, the details of intraoperative difficulties have been poorly described in previous large‐scale studies. In anecdotal reports, 22 , 23 , 24 , 29 , 30 , 31 16.1%–30% of patients received sleeve lobectomy after chemoimmunotherapy, and even one patient received autogenous lobar transplantation. 29 Deng et al 30 reported that 48.4% of patients (15/31) had dense adhesions in the fissure or nodal stations after neoadjuvant chemoimmunotherapy.…”

Section: Discussionmentioning

confidence: 99%

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A real‐world comparison between neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable non‐small cell lung cancer

Zhang

Xiao

et al. 2022

Cancer Medicine

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Background The impact of neoadjuvant chemoimmunotherapy on pulmonary resection and related outcomes had been poorly reported in previous studies. The present study aims to clarify the efficacy and safety of neoadjuvant chemoimmunotherapy, and intraoperative difficulty in the following surgery, in comparison with chemotherapy alone in non‐small cell lung cancer (NSCLC). Methods Patients with newly diagnosed clinical stages IB–IIIB(T3‐4N2) NSCLC, received neoadjuvant chemotherapy + PD‐1 inhibitors (PD‐1 + Chemo group) or chemotherapy alone (Chemo group) followed by surgery between December 2018 and December 2020 were included. The clinicopathological characteristics were retrospectively reviewed and analyzed. Results There were 69 NSCLC patients in the PD‐1 + Chemo group and 121 in the Chemo group. The major pathological response (MPR) rate in the PD‐1 + Chemo group was 49.3%, higher than that of 19.0% in the Chemo group ( p < 0.001). The 2‐year disease‐free survival (DFS) rate was 79.3% and 60.2%, respectively, in the two groups ( p = 0.048). Multivariate analysis identified surgical radicality (hazard ratio (HR), 2.954, 95% confidence interval (CI), 1.527–5.714, p = 0.001), and pathological response (MPR(CR) vs. SD(PD), HR, 0.248, 95% CI, 0.107–0.572, p = 0.001) to be independent prognostic factors for DFS. Lobectomy was performed in 73.9% and 66.1% of patients, respectively, and bronchial sleeve resection/bronchoplasty rate was also comparable (43.4% vs. 40.5%, p = 0.688). More patients in the PD‐1 + Chemo group received vascular sleeve resection/angioplasty (15.9% vs. 6.6%, p = 0.039) and pericardial resection (10.1% vs. 2.5%, p = 0.038). After propensity score matching analysis, pericardial resection rate was still slightly higher in the PD‐1 + Chemo group (9.4% vs. 1.6%, p = 0.05). Perioperative morbidities within 30 days and mortality in 90 days were comparable between groups ( p > 0.05). Conclusions Neoadjuvant chemoimmunotherapy for NSCLC is safe and feasible, with higher MPR rates, as well as favorable DFS than chemotherapy alone. Surgical complexity might be increased in certain patients, with comparable perioperative morbidity and mortality.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

A real‐world comparison between neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable non‐small cell lung cancer

Zhang

Xiao

et al. 2022

Cancer Medicine

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“…Published case reports have detailed the outcomes of surgery following immunochemotherapy for stages IIIB-IV lung cancer that achieved a clinical downstaging (23,(46)(47)(48)(49)(50). Furthermore, a few cohort studies involving patients with IIIB diseases (15,23,34,(51)(52)(53) demonstrated that surgeons in experienced centers can safely operate on advanced NSCLCs that re-enter resectability after immunotherapy or its combination with chemotherapy. Moreover, postoperative survival dramatically improved in these patient cohorts compared to those that did not receive surgery (23,53).…”

Section: Discussionmentioning

confidence: 99%

Preoperative immunochemotherapy for locally advanced non-small cell lung cancer: an analysis of the clinical outcomes, optimal number of cycles, and peripheral immune markers

Deng¹,

Liang²,

Chen³

et al. 2022

Transl Lung Cancer Res

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Background: This retrospective study aimed to evaluate the real-world efficacy of neoadjuvant immunochemotherapy in locally advanced stage III non-small cell lung cancer (NSCLC), with a particular focus on analyzing the optimal treatment cycle and peripheral immune markers.Methods: Eligible patients with biopsy-confirmed stage III NSCLC who underwent neoadjuvant immunochemotherapy between January 1 st , 2018 and March 30 th , 2021 were identified, and their oncological outcomes were collected.Results: A total of 115 patients were identified, among whom 61, 51, and three cases were classified as clinical stage IIIA, IIIB, and IIIC at presentation, respectively. The objective response rate was 61.7% (71/115) after immunochemotherapy. The most frequent surgical procedure was lobectomy, performed in 91 (79.1%) cases, and all patients had microscopic-free margins. Major pathological response (MPR) was observed in 64 (55.7%) patients, among whom 44 (38.3%) achieved a complete pathological response; pathological-confirmed lymph node downstage (cN2-3 to ypN0-1) was described in 73.6% (67/91) of patients with cN2-3 diseases. The median disease-free survival (DFS) of all enrolled patients was 23.6 [95% confidence interval (CI): 15.9-31.3] months, while for patients with residual tumors of more than 10%, the median DFS was 18.1 (95% CI: 12.5-23.8) months. The post-hoc analysis showed that three [odds ratio (OR), 95% CI: 4.10, 0.79-21.32] and four (OR: 7.75, 95% CI: 1.03-58.58) cycles of neoadjuvant immunochemotherapy were prone to higher MPR rates compared to two cycles in patients that were classified as complete/partial response (CR/PR). However, adding over five cycles was not associated with a higher MPR rate (OR, 95% CI: 1.00, 0.16-6.37). The pretreatment lymphocyte count level (1.89±0.68 vs. 1.59±0.63, P=0.019) and monocyte count level (0.71±0.32 vs. 0.59, P=0.020) were significantly higher in MPR patients compared to non-MPR patients. Conclusions:The present study confirmed a favorable real-world tumor downstage efficacy of neoadjuvant immunochemotherapy in locally advanced NSCLC. Even though CR/PR was achieved, it is still beneficial when extended into 3-4 cycles of neoadjuvant immunochemotherapy.

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“…In locally advanced LUAD, immunotherapy with or without chemotherapy has been one of the first‐line treatment choices in specific cases 29,30 . In addition, neoadjuvant chemoimmunotherapy, including pembrolizumab, sintilimab or nivolumab, is currently of great interest in IIB–IIIA stage LUAD patients who undergo complete resection, which leads to a major pathological response in 46%–64% as a real‐word outcome 31,32 . Additional clinical trials on the outcome of neoadjuvant chemoimmunotherapy for locally advanced NSCLC are ongoing, and results are expected in the coming years.…”

Section: Discussionmentioning

confidence: 99%

“…29,30 In addition, neoadjuvant chemoimmunotherapy, including pembrolizumab, sintilimab or nivolumab, is currently of great interest in IIB-IIIA stage LUAD patients who undergo complete resection, which leads to a major pathological response in 46%-64% as a realword outcome. 31,32 Additional clinical trials on the outcome of neoadjuvant chemoimmunotherapy for locally advanced NSCLC are ongoing, and results are expected in the coming years. It will be interesting to test the association between LUAD histologic pattern and response to immune checkpoint inhibitors in both adjuvant and neo-adjuvant chemoimmunotherapy.…”

Section: Fap Is Downstream Effector Of Cgas-sting Pathway Activationmentioning

confidence: 99%

Characterization of the evolution trajectory and immune profiling of new histologic patterns in lung adenocarcinoma

Song

Xie

Liu

et al. 2022

The Journal of Gene Medicine

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In lung adenocarcinoma (LUAD), the appearance of morphologically diverse tumor regions, termed histological patterns, is closely associated with disease progression and lymph node metastasis. However, the molecular characteristics of the histological patterns in LUAD and the underlying molecular evolutionary mechanisms between the histological patterns in primary tumors and lymph node metastases are poorly understood. Here, we re-analyzed the large TCGA-LUAD dataset and depicted a comprehensive profiling of the genome and transcriptome across the histological patterns in LUAD. Tumor phylogenetic trajectory analysis suggested that the complex glands is more apt to metastasize to the lymph node. Further deconvolution of the tumor microenvironment demonstrated that the complex glands had a higher infiltration of cancer-associated fibroblasts (CAFs). Single-cell transcriptome profiling of complex glands pattern identified a novel CAF subtype co-expressing fibroblast activation protein-alpha (FAP) and stimulator of interferon genes (STING). Moreover, our data demonstrated that FAP is an important downstream effector of STING in CAFs.In summary, our results provide the basis for the development of innovative therapeutic guidelines and intervention strategies for LUAD patients.

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Real-world clinical outcomes of neoadjuvant immunotherapy combined with chemotherapy in resectable non-small cell lung cancer

Cited by 24 publications

References 39 publications

A real‐world comparison between neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable non‐small cell lung cancer

A real‐world comparison between neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable non‐small cell lung cancer

Preoperative immunochemotherapy for locally advanced non-small cell lung cancer: an analysis of the clinical outcomes, optimal number of cycles, and peripheral immune markers

Characterization of the evolution trajectory and immune profiling of new histologic patterns in lung adenocarcinoma

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