Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1)

Li, Chengqiang; Zhao, Shihua; Zheng, Yuyan; Han, Yichao; Chen, Xiaoyan; Cheng, Zenghui; Wu, Yuquan; Feng, Xiaoyuan; Qi, Wei-Xiang; Chen, Kai; Xiang, Jie; Li, Jian; Lerut, Toni; Li, Hecheng

doi:10.1016/j.ejca.2020.11.039

Cited by 201 publications

(237 citation statements)

References 36 publications

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“…[8][9][10][11][12][13][14][15][16] It is still uncertain whether a PD-1 inhibitor could change the paradigm of esophageal cancer treatment, in particular whether it could finally improve long-term survival. Because many clinicians are investigating preoperative immunotherapy, [17][18][19][20] there is an urgent need to evaluate the safety of surgery after PD-1 inhibitor treatment. With good communication between clinicians and patients, and strict ethical supervision, it is reasonable to include immunotherapy in the preoperative setting and to perform surgery for unresectable locally advanced esophageal cancer as evaluated at baseline examination.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of programmed cell death protein 1 inhibitor in resection transformation treatment of esophageal cancer

et al. 2021

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Background: Surgery is an important component in the treatment of esophageal cancer. For patients not eligible for R0 resection, defined as locally advanced unresectable esophageal cancer, a new approach is to transform the cancer into a resectable state by preoperative treatment. However, preoperative chemo/radiation is unsatisfactory. Therefore, the aim of this study was to assess the safety and efficacy of chemo/radiotherapy combined with a programmed cell death protein 1 (PD-1) inhibitor in the preoperative transformation of unresectable esophageal cancer. Methods: Patients were evaluated as having unresectable, locally advanced esophageal cancer at baseline and were re-evaluated as possible R0 resection candidates after PD-1 inhibitor treatment. Patient data were derived from the prospective database of Peking University Cancer Hospital Thoracic Surgery I. Preoperative chemotherapy plus PD-1 inhibitor treatment was defined as "transformation treatment." The objective response rate, operation rate (proportion of patients who underwent surgery), R0 rate, and treatment safety were analyzed retrospectively. Results: A total of 36 patients were enrolled into the study, and 94.4% (34/36) completed the planned transformation treatment. The objective response rate was 71.4% (25/35), and 75% (27/36) of the patients who completed transformation treatment underwent surgery. For these surgical patients, 81.5% (22/27) obtained R0 resection, and 22.2% (6/22) had pathological complete response (pCR). During transformation treatment, 22.2% (8/36) patients had ≥ grade 3 complications. There were no reoperations or perioperative deaths. After surgery, 29.6% (8/27) had ≥ grade 3 complications. Conclusions: Esophagectomy after immunotherapy is safe with acceptable complications. Compared with chemotherapy alone, chemotherapy combined with immunotherapy had a more favorable transformation effect for patients with unresectable esophageal cancer.

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Section: Introductionmentioning

confidence: 99%

Efficacy of programmed cell death protein 1 inhibitor in resection transformation treatment of esophageal cancer

et al. 2021

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“…However, comparing the two studies with the Cross trial and NEOCRTEC5010 trial (24,25), we found that the pCR rates of the combination of neoadjuvant pembrolizumab and chemotherapy did not significantly improve over neoadjuvant chemotherapy, even patients had to bear the additional side effects of the immune checkpoint inhibitors. The PALACE-1 study showed that PD-L1 expression was not associated with pathological response, while TCF-1+ and CD8+ T cell infiltrates in tumors with PCR were significantly higher than those in tumors without PCR (9). Therefore, the method of predicting whether or not resectile EC patients will achieve PCR after neoadjuvant pembrolizumab combined with chemoradiotherapy remains unclear and needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…A phase I trial (PALACE-1) conducted by Li et al explored the safety of preoperative pembrolizumab combined with chemoradiotherapy for ESCC (9). Twenty patients with resectable ESCC received preoperative pembrolizumab with concurrent chemoradiotherapy (PPCT), regardless of PD-1 status.…”

Section: Treatment Of Resectable Ecmentioning

confidence: 99%

“…Programmed cell death protein 1 (PD-1) inhibitors can facilitate the elimination of such tumors by the immune system by inhibiting immune checkpoint (7,8). Several early trials suggest that immune checkpoint inhibitor like pembrolizumab may have some efficacy for the treatment of advanced EC and the neoadjuvant treatment of EC (9)(10)(11)(12)(13)(14). Pembrolizumab was approved by the United States Food and Drug Administration (USFDA) in 2014 for the second-line or multi-line treatment of patients with any unresectable or metastatic solid tumor; in 2019, it was approved for the second-line treatment of patients with programmed death-ligand 1 (PD-L1)-positive, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) (15).…”

Section: Introductionmentioning

confidence: 99%

“…Pembrolizumab was approved by the United States Food and Drug Administration (USFDA) in 2014 for the second-line or multi-line treatment of patients with any unresectable or metastatic solid tumor; in 2019, it was approved for the second-line treatment of patients with programmed death-ligand 1 (PD-L1)-positive, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) (15). Since 2020, the results of the PALACE-1 trial for resectable EC have been announced, and phased data from the NCT02844075 trial and KEYNOTE-590 trial have also been published (9,10,14). In March 2021, the USFAD approved pembrolizumab as a first-line treatment for advanced esophageal cancer.…”

Section: Introductionmentioning

confidence: 99%

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Narrative review of pembrolizumab for the treatment of esophageal cancer: evidence and outlook

Jin¹,

Shen²,

Wang³

et al. 2021

Ann Transl Med

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Objective: Based on the current evidence, review the efficacy and safety profile of pembrolizumab, along with its shortcomings, in an effort to define future research directions. Background: The survival outcome of esophageal cancer (EC) is poor, especially in patients with advanced stage. Palliative surgery, chemotherapy, radiotherapy and chemoradiotherapy have limited efficacy in prolonging the survival time. Currently, immunotherapies, including adoptive cell therapy-based, antibodybased, and vaccine-based therapies, are attracting considerable attention. The mechanism of immunotherapy lies in the modification of immune response and prevention of immune escape. Immunomodulatory agents can block the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway, thereby allowing lymphocytes to attack tumor cells. This class of drugs has the potential to treat a variety of tumors and may substantially improve overall survival (OS) in some patients. Multiple clinical trials have shown that pembrolizumab has good efficacy and safety, enhances the EC treatment paradigm, and has even become the first-line treatment of choice for patients with PD-L1-positive recurrent or metastatic EC. Methods: We reviewed the results of clinical trials of pembrolizumab for EC and gastroesophageal cancer presented at Embase, PubMed, the American Society of Clinical Oncology (ASCO) annual meetings, and the Cochrane Central Register of Controlled Trials.Conclusions: Pembrolizumab has good efficacy and tolerability profiles, and has emerged as a second-line option for the treatment of PD-L1-positive locally advanced or metastatic ESCC. Pembrolizumab has many promising applications, and further investigations into its mechanisms should be conducted.

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Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer

Huo

et al. 2022

JAMA Netw Open

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ImportanceA considerable number of clinical trials of neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations of these studies are lacking.ObjectiveTo provide state-of-the-art evidence and normative theoretical support for neoadjuvant immunotherapy for locally advanced resectable esophageal cancer.Data SourcesPubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant original articles and conference proceedings that were published in English through April 1, 2022.Study SelectionPublished phase 2 or 3 clinical trials that included patients with resectable stage I to IV esophageal cancer who received immune checkpoint inhibitors (ICIs) before surgery as monotherapy or in combination with other therapies.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines for meta-analysis were followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 statistic &gt;50%); otherwise, the common-effects model was used. Data analyses were conducted from April 2 to 8, 2022.Main Outcomes and MeasuresPathological complete response (pCR) rate and major pathological response (MPR) rate were considered to be the primary outcomes calculated for the clinical outcomes of neoadjuvant immunotherapy. Incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. The rate of R0 surgical resection was summarized. Subgroup analyses were conducted according to histologic subtype and ICI types.ResultsA total of 27 clinical trials with 815 patients were included. Pooled rates were 31.4% (95% CI, 27.6%-35.3%) for pCR and 48.9% (95% CI, 42.0-55.9%) for MCR in patients with esophageal cancer. In terms of safety, the pooled incidence of treatment-related severe adverse events was 26.9% (95% CI, 16.7%-38.3%). Most patients achieved R0 surgical resection (98.6%; 95% CI, 97.1%-99.6%). Regarding histologic subtypes, the pooled pCR rates were 32.4% (95% CI, 28.2%-36.8%) in esophageal squamous cell carcinoma and 25.2% (95% CI, 16.3%-35.1%) in esophageal adenocarcinoma. The pooled MPR rate was 49.4% (95% CI, 42.1%-56.7%) in esophageal squamous cell carcinoma.Conclusions and RelevanceThis study found that neoadjuvant immunotherapy with chemotherapy had promising clinical and safety outcomes for patients with resectable esophageal cancer. Randomized clinical trials with long-term follow-up are warranted to validate the findings and benefits of ICIs.

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Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1)

Cited by 201 publications

References 36 publications

Efficacy of programmed cell death protein 1 inhibitor in resection transformation treatment of esophageal cancer

Efficacy of programmed cell death protein 1 inhibitor in resection transformation treatment of esophageal cancer

Narrative review of pembrolizumab for the treatment of esophageal cancer: evidence and outlook

Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer

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