Expert consensus on neoadjuvant immunotherapy for non-small cell lung cancer

Liang, Wenhua; Cai, Kaican; Chen, Chun; Chen, Haiquan; Chen, Qixun; Fu, Junke; Hu, Jian; Jiang, Tao; Jiao, Wenjie; Li, Shuben; Liu, Deruo; Liu, Wei; Liu, Yang; Ma, Haitao; Pan, Xiaojie; Qiao, Guibin; Tian, Hui; Li, Wei; Zhang, Yi; Zhao, Song; Zhao, Xiaojing; Zhou, Chengzhi; Zhu, Yuming; Zhong, Ran; Li, Feng; Rosell, Rafael; Provencio, Mariano; Massarelli, Erminia; Antonoff, Mara B.; Hida, Toyoaki; Perrot, Marc de; Lin, Steven H.; Maïo, Massimo Di; Rossi, Antonio; Ruysscher, Dirk De; Ramirez, Robert A.; Dempke, Wolfram; Camidge, D. Ross; Guibert, Nicolas; Califano, Raffaele; Wang, Qi; Ren, Shengxiang; Zhou, Caicun; He, Jianxing

doi:10.21037/tlcr-2020-63

Cited by 54 publications

(47 citation statements)

References 71 publications

(95 reference statements)

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“…Three of the PR patients turned out to have a pCR in resected tissue. This was consistent with previous observation that evaluation per RECIST criteria may not truly reflect actual benefit from immunotherapy (9). Of note, the surgical resections of the responders showed an inflamed phenotype with a massive influx of multinucleated giant cells and lymphocytes compared to baseline biopsy samples, a phenomenon typically associated with response to immune checkpoint blockade, which may help explain the minimal tumor shrinkage or even tumor enlargement seen in the CT scans of some responders (Figure 1C).…”

Section: Clinical and Pathological Responsessupporting

confidence: 90%

“…In recent years, anti-programmed death-1 (PD-1)/antiprogrammed death-ligand 1 (PD-L1) has demonstrated great promise in unresectable ESCC patients, and thus has been approved by the Food and Drug Administration as second-line treatment in this population (7,8). In addition, neoadjuvant administration of anti-PD-1 in other malignancies such as lung cancer, melanoma and colorectal cancer has also produced durable responses with favorable tolerability (9)(10)(11). Multiple trials are therefore currently underway to exploit preoperative use of anti-PD-1/PD-L1 in locally advanced ESCC, most of which combined anti-PD-1/PD-L1 with chemotherapy or chemoradiation.…”

Section: Introductionmentioning

confidence: 99%

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Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma

Yang¹,

Su²,

Yang³

et al. 2021

Ann Transl Med

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Background: Immunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC.Methods: Patients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated.Results: Twelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs).Conclusions: Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.

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Section: Clinical and Pathological Responsessupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma

Yang¹,

Su²,

Yang³

et al. 2021

Ann Transl Med

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“…Supported by NCCN guidelines, PET-CT is considered to be relatively better method to predict curative effect of neoadjuvant immunotherapy in NSCLC ( 10 , 11 ). However, the results of preoperative PET-CT, which showed that residual metabolic-active areas existed, were not completely consistent with the result of postoperative pathology, which showed a pCR, indicating that PET-CT maybe not good enough to be an independent predictive marker of pCR in this case.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Pathological Complete Response in a Brain-Metastatic Lung Squamous Cell Carcinoma Patient With Long-Term Benefit From Chemo-Immunotherapy

et al. 2021

Front. Oncol.

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Immune checkpoint inhibitors have brought long-term survival benefit in advanced non-small cell lung cancer patients without driver gene mutations. Even after withdrawal of immunotherapy for a maximum of two years, some patients still benefit from this therapy and the reason is not fully clear. Results from several neoadjuvant trials indicated that in resectable lung cancer patients, neoadjuvant immunotherapy or chemo-immunotherapy led to major or complete pathological responses in a high proportion of tumors. Here we report a case of a brain-metastatic lung squamous cell carcinoma patient who received supratentorial tumor resection and thoracic surgery after chemo-immunotherapy, and achieved a pathological complete response (pCR) in both lesions. This case indicated that pCR can also happen in advanced-stage lung cancer patients receiving chemo-immunotherapy, which may be the reason for long-term benefit of those patients.

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“…Our observation is consistent with previous reports that pCR patients may nonetheless experience tumor recurrence 23,24 . A consensus strategy for management of pCR patients after neoadjuvant immunotherapy has not been established due to lack of de nitive clinical evidence, although one year of maintenance immunotherapy has been recommended 25 . Our observation of malignant cells by scRNA-seq that were not detectable by traditional histopathology provides support for maintenance immunotherapy for pCR patients.…”

Section: Combined Therapymentioning

confidence: 99%

“…This may represent a novel strategy to eliminate the residual cancer cells in MPR patients. For example, the combination of SERPINB9 inhibitors with ICB may further the survival of MPR patients after neoadjuvant immunotherapy, while the consensus recommends only ICB maintenance therapy 25 .…”

Section: Distinct Molecular Characteristics Of Malignant Cells Distinguish Mpr and Nmprmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Tumor Microenvironment Remodeling after Neoadjuvant Immunotherapy in Non-small Cell Lung Cancer

Hu¹,

zhang²,

Xia³

et al. 2021

Preprint

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Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance. To explore immunotherapy resistance mechanisms, we characterized the transcriptomes of ~92000 single cells from 15 patients with non-small cell lung cancer (NSCLC) during neoadjuvant PD-1 blockade combined with chemotherapy. CD8+ T, natural killer, B, and dendritic cells were activated by therapy. Therapy also promoted differentiation of memory T cells into effector T cells. Macrophages were remodeled into an M0-like phenotype and neutrophils into an aged phenotype. Distinct therapy-induced cancer-cell transcriptomes were associated with clinical response. Major pathologic responders (MPRs) activated antigen presentation via major histocompatibility complex class II (MHC-II). Cancer cells of non-MPRs exhibited overexpression of estrogen metabolism enzymes and elevated serum estradiol. Elevated estradiol activated EGFR signaling and upregulated the expression of VEGFA, which promoted an immunosuppressive microenvironment. FCRL4+FCRL5+ memory B cells and CD16+CX3CR1+ monocytes were identified as biomarkers for positive immunotherapy response.

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Expert consensus on neoadjuvant immunotherapy for non-small cell lung cancer

Cited by 54 publications

References 71 publications

Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma

Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma

Case Report: Pathological Complete Response in a Brain-Metastatic Lung Squamous Cell Carcinoma Patient With Long-Term Benefit From Chemo-Immunotherapy

Single-Cell RNA Sequencing Reveals Tumor Microenvironment Remodeling after Neoadjuvant Immunotherapy in Non-small Cell Lung Cancer

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