Progression‐free survival at 3 years is a reliable surrogate for 5‐year overall survival for patients suffering from locally advanced esophageal squamous cell carcinoma

Yang, Yuxian; Zheng, Yuzhen; Gao, Tiantian; Liu, Shiliang; Xi, Mian; Liu, Meng‐Zhong; Wang, Junye; Qi, Shunan; Yang, Yong; Zhao, Lei

doi:10.1002/cam4.4751

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…As far as we know, this was the first study to identify PFS-based endpoints systematically in advanced ESCC patients receiving immunotherapy in combination with chemotherapy as 1-L treatment. Previous studies have shown that three-year PFS is a reliable SE of 5-year OS in locally advanced ESCC treated with definitive RT; when treating resectable ESCC and esophageal adenocarcinoma (EAC) and gastroesophageal junction (GEJ) cancer, HR PFS can be used in neoadjuvant, perioperative, or adjuvant settings as a substitute for HR OS ; in addition, in neoadjuvant RCTs of gastric carcinoma(GC) and GEJ adenocarcinoma, event-free survival (EFS) could serve as a SE [ 35 – 37 ]. However, in the immune-oncology (IO) era, due to the special response patterns of Immuno-checkpoint inhibitors (ICIs) such as pseudoprogression and delayed response, whether the traditional SE for OS is applicable to IO trials is controversial [ 38 – 40 ].…”

Section: Discussionmentioning

confidence: 99%

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma—an exploration of surrogate endpoint

et al. 2023

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Background Overall survival (OS) is the gold standard to assess novel therapeutics to treat cancer. However, to identify early efficacy and speed up drug approval, trials have used progression-free survival (PFS) as a surrogate endpoint (SE). Herein, we aimed to examine if PFS could function as an OS surrogate in advanced Esophageal Squamous Cell Carcinoma (ESCC) treated with first-line immunochemotherapy. Methods Two hundred ninety-two advanced ESCC patients treated using inhibitors of PD-1/PD-L1 + chemotherapy or chemotherapy alone were collected. In addition, six phase III randomized clinical trials were eligible for inclusion. Bayesian normal-induced-copula-estimation model in retrospective patient data and regression analysis in the published trial data were used to determine the PFS-OS correlation. Results PFS correlated moderately with OS in the retrospective cohort (Kendall’s Tau = 0.684, τ = 0.436). In trial-level, treatments effects for PFS correlated weakly with those for OS in intention-to-treat population (R2 = 0.436, adj.R2 = 0.249, P > 0.05) and in PD-L1-enriched population (R2 = 0.072). In arm-level, median PFS also correlated weakly with median OS. Moreover, analysis of the retrospective cohort demonstrated that the annual death risk after progression in the continued immunotherapy group was considerably lower than that in the discontinued group. Conclusion In trials of anti-PD-1 agents to treat advanced ESCC, the current results provide only weak support for PFS as an OS surrogate; OS cannot be substituted completely by PFS in these cases. The results also suggest that qualified patients with advanced ESCC might benefit from continuous immunotherapy beyond progression to achieve a decreased risk of death.

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Section: Discussionmentioning

confidence: 99%

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma—an exploration of surrogate endpoint

et al. 2023

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“…Investigating the correlation between the clinical endpoint OS and potential short-term outcome of interest, such as ORR, MRD-negative CR, PFS, or EFS [19,20], can accelerate the development of new drugs. This approach has been identified in several malignant hematological tumors [21], we similarly assessed the correlation in the included data.…”

Section: Correlation Between Orr Mrd-negative Cr Pfs and Osmentioning

confidence: 99%

Difference in Efficacy and Safety of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Containing 4-1BB and CD28 Co-Stimulatory Domains for B-Cell Acute Lymphoblastic Leukemia

Chen

Cai

et al. 2023

Cancers

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This study quantified the differences in the efficacy and safety of different stimulation domains of anti-CD19 chimeric antigen receptor (CAR) T therapy for B-cell acute lymphoblastic leukemia (B-ALL). Clinical trials related to anti-CD19 CAR T-cell therapy for B-ALL were searched in public databases from database inception to 13 November 2021. The differences in overall survival (OS) and progression-free survival (PFS) of B-ALL patients treated with anti-CAR T-cell therapy containing 4-1BB and CD28 co-stimulatory domains were compared by establishing a parametric survival function. The overall remission rate (ORR), the proportion of people with minimal residual disease (MRD)-negative complete remission (CR), the incidence of cytokine release syndrome (CRS), and the neurotoxicity across different co-stimulatory domains was assessed using a random-effects model. The correlation between the ORR, MRD-negative CR, PFS, and OS was tested. The results showed that the median OS of anti-CAR T-cell treatment containing 4-1BB and CD28 co-stimulatory domains was 15.0 months (95% CI: 11.0–20.0) and 8.5 months (95% CI: 5.0–14.0), and the median PFS was 7.0 months (95% CI: 4.0–11.5) and 3.0 months (95% CI: 1.5–7.0), respectively. Anti-CD19 CAR T-cells in the 4-1BB co-stimulatory domain showed superior benefits in patients who achieved ORR. The incidence of neurotoxicity was significantly higher in the CD28 co-stimulatory domain of anti-CD19 CAR T-cells than in the 4-1BB co-stimulatory domain. In addition, the ORR and MRD-negative CR were strongly correlated with OS and PFS, and PFS and OS were strongly correlated. The 4-1BB co-stimulatory domain suggested a better benefit–risk ratio than the CD28 co-stimulatory domain in B-ALL.

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“…However, a considerable number of EC patients still develop metastasis and recurrence after surgery. The 5-year survival rate of EC patients after surgery is <20% ( 8 ). EC seriously endangers the health of people all over the world.…”

Section: Introductionmentioning

confidence: 99%

Bufalin suppresses esophageal squamous cell carcinoma progression by activating the PIAS3/STAT3 signaling pathway

Ju¹,

Shi²,

Liu³

et al. 2023

J Thorac Dis

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Background: Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is a common malignant tumor of the digestive tract. Bufalin is an effective anti-tumor compound. However, little is known about the regulatory mechanisms of Bufalin in ESCC. To investigate the effect and molecular mechanism of Bufalin on the proliferation, migration and invasion of ESCC cells will provide a more reliable basis for the application of Bufalin in clinical tumor therapy.Methods: First, the half-inhibitory concentration (IC50) of Bufalin was evaluated by Cell Counting Kit-8 (CCK-8) assays. In vitro, the effects of Bufalin on the proliferation of the ECA109 cells was measured using CCK-8 and 5-ethynyl-2'-deoxyuridine assays. Wound-healing and transwell assays were used to evaluate the effects of Bufalin on the migration and invasion of the ECA109 cells. Further, to determine the mechanisms underlying the Bufalin-mediated suppression of cell progression in ESCC, total RNA was extracted from negative control (NC) and Bufalin treated cells to perform RNA-sequencing (RNA-seq) to screen for abnormally expressed genes. In vivo, the ECA 109 cells were subcutaneously injected into BALB/c nude mice to determine the effects of Bufalin on tumor cell proliferation. The protein inhibitor of activated signal transducer and activator of transcription 3 (PIAS3), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3) protein expression levels in the ECA109 cells were detected by Western blot. Results:The CCK-8 assays showed that the IC50 of Bufalin was 200 nM. The proliferation, migration, and invasion ability of the ECA109 cells was significantly inhibited in the Bufalin group in a concentrationdependent manner. In vivo, the Xenograft tumor model showed that Bufalin decreased the tumor volume and weight of the subcutaneous tumors. The RNA-seq results showed that the expression of PIAS3 was upregulated in the Bufalin group. Additionally, down-regulation of PIAS3 decreased the inhibition of STAT3, thereby increasing p-STAT3 expression. Finally, PIAS3 knockdown reversed the inhibitory effects of Bufalin on the proliferation, migration, and invasion of the ECA109 cells.Conclusions: Bufalin may inhibit the proliferation, migration, and invasion of the ECA109 cells through the PIAS3/STAT3 signaling pathway.

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Progression‐free survival at 3 years is a reliable surrogate for 5‐year overall survival for patients suffering from locally advanced esophageal squamous cell carcinoma

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 41 publications

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma—an exploration of surrogate endpoint

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma—an exploration of surrogate endpoint

Difference in Efficacy and Safety of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Containing 4-1BB and CD28 Co-Stimulatory Domains for B-Cell Acute Lymphoblastic Leukemia

Bufalin suppresses esophageal squamous cell carcinoma progression by activating the PIAS3/STAT3 signaling pathway

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