Esophageal Squamous Cell Carcinoma In China Research Articles

Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts

BackgroundThis study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China.MethodsFrom February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1–6 and the second for cases 7–9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test.ResultsThe second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76–0.81; mean Hmean = 2.11–3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63–0.64; mean Hmean = 5.66–7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature.ConclusionsWe have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.

398. DYSPHAGIA OR REGURGITATION AND ITS CORRELATES AMONG UP TO 10-YEAR ESOPHAGEAL SQUAMOUS CELL CARCINOMA SURVIVORS

Abstract Background Dysphagia and regurgitation significantly impair the quality of life among survivors of esophageal squamous cell carcinoma (ESCC). Notably, the prevalence and associated factors of these symptoms in long-term survivors, particularly within Asian populations, remain underexplored. This study endeavors to bridge these critical knowledge gaps. Methods We evaluated the severity of dysphagia and regurgitation (mild, moderate, and severe), and their associations with clinical features and lifestyle factors among 512 10-year ESCC survivors who underwent ESCC radical surgery. Demographic, clinical, and lifestyle information was collected at study enrollment, which occurred 6 months post-surgery, and dysphagia and regurgitation was assessed at the 10-year post-surgery follow-up survey. Results In this study, 13.3% and 27.0% of participants reported dysphagia and regurgitation, respectively. Multivariable polytomous regression analysis revealed a significant association of dysphagia with upper thoracic esophageal carcinoma (mild dysphagia OR: 2.371, 95% CI: 1.051, 5.347) and postoperative radiotherapy and chemotherapy (mild dysphagia OR: 4.352, 95% CI: 2.168, 8.732; moderate/severe dysphagia OR: 3.651, 95% CI: 1.046, 12.745). An inverse relationship was observed between dysphagia and dietary quality as measured by the CHFP-2007 score (mild dysphagia OR: 0.458, 95% CI: 0.341, 0.615; moderate/severe dysphagia OR: 0.168, 95% CI: 0.089, 0.316). For regurgitation, positive associations were found with higher income level (mild regurgitation OR: 2.074, 95% CI: 1.020, 4.216), insomnia (moderate/severe regurgitation OR: 3.523, 95% CI: 1.127, 11.010), and use of Chinese patent medicine (mild regurgitation OR: 2.264, 95% CI: 1.279, 4.007). Conversely, age at surgery (moderate/severe dysphagia OR: 0.907, 95% CI: 0.848, 0.970) and higher dietary quality (mild dysphagia OR: 0.744, 95% CI: 0.606, 0.914; moderate/severe dysphagia OR: 0.406, 95% CI: 0.259, 0.634) showed protective effects against regurgitation. Conclusions The prevalence of dysphagia and regurgitation among long-term survivors of ESCC in China is high, underscoring a significant health concern. This study identifies critical correlates such as the tumor's anatomical site, the nature of postoperative interventions, dietary quality, socioeconomic standing, and concurrent health issues. These findings advocate for the integration of postoperative management approaches, including tailored dietary and lifestyle adjustments, aimed at mitigating these symptoms in long-term ESCC survivors.

The feasibility and tolerability of anlotinib plus PD-1 blockades among patients with previously immunotherapy treated advanced esophageal squamous cell carcinoma (ESCC): Update results of a retrospective exploratory study.

e16006 Background: Immunotherapy (ICI) demonstrated promising efficacy for patients with advanced ESCC in both second-line and first-line treatment clinically. Therefore, whether the patients might benefit from the PD-1 blockades-related regimens when they failed after the previous ICI remained to be identified and the feasibility of PD-1 blockades rechallenge in ESCC was warranted to be explored. As a novel oral multi-targeted tyrosine kinase inhibitor (TKI) for tumor angiogenesis and proliferation, anlotinib was an efficacious second-line monotherapy for ESCC in China and the combination of anlotinib plus PD-1 blockades might be a promising strategy for patients with previously ICI treated advanced ESCC. Methods: This multicenter, retrospective study was planned to include 110 patients with previously ICI treated advanced ESCC from 9 hospitals in China who were treated with anlotinib plus PD-1 blockades in clinical practice from July 2018 to November 2022 consecutively. The Outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. Results: At the date of data-cutoff (May 12 2023), 110 eligible patients were available to be analyzed. Characteristics were as follows: median age of 64 years, male/female 74.5%/25.5%, ECOG PS 0/1/2 22.7%/75.5%/1.8%, clinical stage II/III/IV 0.9%/20.9%/78.2%. All the patients had received ICIs and 10.9% patients were treated with TKIs previously. 39.1% patients had received first-line therapy, 41.8% patients had received second-line, 19.1% patients had received third or above line previously. Prognostic outcomes exhibited that the median OS was 11.1 months (95%CI: 8.6-13.7), 12-month OS rate, 24-month OS rate were 47.6% and 30.8%, separately. Additionally, the median PFS was 5.6 months (95%CI: 4.4-6.8). In 110 patients, ORR was 19.1% (95%CI: 12.2%-27.7%), DCR 69.1% (95%CI: 59.6%-77.6%). Safety profile of anlotinib plus PD-1 blockades indicated that the treatment related adverse events (TRAEs) were 89.1%. The most common TRAEs were anaemia (62.7%), hypothyroidism (25.5%), hypoalbuminemia (21.8%), lymphocytopenia (20%), leukopenia (19.1%). Conclusions: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and tolerable adverse reactions among patients with advanced ESCC who had received immunotherapy previously and the feasibility of PD-1 blockades rechallenge in ESCC was promising to be elucidated. Clinical trial information: ChiCTR2300070777.

Update results of anlotinib combined with penpulimab and nab-paclitaxel as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial.

e16017 Background: Recently, PD-1 blockades combined with dual chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC. However, the safety profile of conventional dual chemotherapy remained unsatisfactory. Therefore, PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) and single chemotherapy regimen might be a promising strategy. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as first-line combination therapy or second-line monotherapy for patients with ESCC in China clinically. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with penpulimab (PD-1 blockade) and nab-paclitaxel as first-line therapy in advanced ESCC. Preliminary results were presented at the 2024 ASCO-GI Symposium (Abs 340), the consecutively updated results were presented in this report. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and treated with anlotinib (12mg, po, d1~14, q3w) and penpulimab (200mg, iv, d1, q3w) plus nab-paclitaxel (220mg/m2, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 30. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and OS. Results: From Jul 2022 to Dec 2023, a total of 27 patients were enrolled, 25 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 1 CR (4.0%), 18 PR (72.0%), 3 SD (12.0%) and 3 NE (12.0%). Therefore, the preliminary ORR was 76.0% (95%CI: 54.9%-90.6%), DCR was 88.0% (95%CI: 68.8%-97.5%). Median PFS of the 25 patients was not yet reached. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 27 patients with the incidence &gt; 20% were anemia (40.7%), peripheral nerve toxicity (37.0) and white blood cell decreased (25.9%). Common grade ≥3 treatment-emergent adverse events were white blood cell decreased (7.4%), diarrhea (3.7%), glutamic-pyruvic transaminase was elevated (3.7%), glutamic oxalacetic transaminase increased (3.7%), hypertension (3.7%) and immune enteritis (3.7%). Conclusions: The combination of anlotinib plus penpulimab and nab-paclitaxel as first-line therapy for advanced ESCC demonstrated promising efficacy and manageable safety profile. And the conclusions needed to be confirmed in subsequent trials.

Cost-effectiveness analysis of tislelizumab vs. camrelizumab for the treatment of second-line locally advanced or metastatic esophageal squamous cell carcinoma

BackgroundEsophageal carcinoma is a type of cancer that occurs in the esophagus. For patients with locally advanced or metastatic esophageal squamous cell carcinoma who have either experienced disease progression following first-line standard chemotherapy or are intolerant to it, the prognosis is typically poor. Additionally, these patients often bear a substantial economic burden during the course of their treatment. Tislelizumab is a selective PD-1 inhibitor with efficacy proven in locally advanced or metastatic esophageal squamous cell carcinoma. The study aims to evaluate the cost-effectiveness of tislelizumab versus camrelizumab as the second-line treatment in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients in China.MethodsFrom the perspective of China’s healthcare system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime horizon. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from RATIONALE 302 trial and the published ESCORT study due to the lack of head-to-head clinical trials. Only direct medical costs were included. Costs and utility values were derived from local charges, the published literature, and related databases. Sensitivity analyses and a scenario analysis were also performed to verify the robustness of the model results.ResultsCompared with camrelizumab monotherapy, tislelizumab monotherapy incurred a lower lifetime cost ($8,346 vs. $8,851) and yielded higher quality-adjusted life-years (QALYs) (0.87 vs. 0.63), which resulted in an incremental cost-effectiveness ratio (ICER) of -$2,051/QALY. Tislelizumab monotherapy is a dominant option over camrelizumab monotherapy in China. The three primary parameters upon which this result was most sensitive were the unit cost of camrelizumab, the unit cost of tislelizumab, and the duration of reactive cutaneous capillary endothelial proliferation (RCCEP). According to the probabilistic sensitivity analysis (PSA), tislelizumab monotherapy was 100% cost-effective when the WTP was 1–3 times GDP per capita in China($11,207/QALY∼$33,621/QALY). Scenario analysis showed that the result was consistent.ConclusionTislelizumab monotherapy is a dominant option compared with camrelizumab monotherapy as the second-line treatment for locally advanced or metastatic ESCC in China.

Immune checkpoint inhibitors as the second-line treatment for advanced esophageal squamous cell carcinoma: a cost-effectiveness analysis based on network meta-analysis

BackgroundImmune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system.MethodsA network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs).ResultsFive clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%.Conclusions and relevanceAmong the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.

Cost-effectiveness analysis of tislelizumab plus chemotherapy as the first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma in China.

We aimed to investigate the cost-effectiveness of tislelizumab plus chemotherapy compared to chemotherapy alone as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (OSCC). A partitioned survival model was developed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic OSCC over a 10-year lifetime horizon from the perspective of the Chinese healthcare system. Costs and utilities were derived from the drug procurement platform and published literature. The model outcomes comprised of costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to address uncertainty and ensure the robustness of the model. Tislelizumab plus chemotherapy yielded an additional 0.337 QALYs and incremental costs of $7,117.007 compared with placebo plus chemotherapy, generating an ICER of $21,116.75 per QALY, which was between 1 time ($12,674.89/QALY) and 3 times GDP ($38,024.67/QALY) per capita. In one-way sensitivity analysis, the ICER is most affected by the cost of oxaliplatin, paclitaxel and tislelizumab. In the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set as 1 or 3 times GDP per capita, the probability of tislelizumab plus chemotherapy being cost-effective was 1% and 100%, respectively. Tislelizumab plus chemotherapy was probably cost-effective compared with chemotherapy alone as the first-line treatment for advanced or metastatic OSCC in China.

A cost-effectiveness analysis of the combination of serplulimab with chemotherapy for advanced esophageal squamous cell carcinoma: insights from the ASTRUM-007 trial

BackgroundCombined serplulimab and chemotherapy demonstrated improved clinical survival outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) and PD-L1 combined positive scores (CPS) ≥ 1. The present study aimed to evaluate the economic viability of integrating serplulimab in combination with chemotherapy as a potential therapeutic approach for treating ESCC in China.MethodsA Markov model was constructed to evaluate the economic and health-related implications of combining serplulimab with chemotherapy. With the incremental cost-effectiveness ratio (ICER), costs and results in terms of health were estimated. For assessing parameter uncertainty, one-way and probabilistic sensitivity studies were carried out.ResultsThe combination of serplulimab and chemotherapy yielded incremental costs and QALYs of $3,163 and 0.14, $2,418 and 0.10, and $3,849 and 0.15, respectively, for the overall population as well as patients with PD-L1 CPS1-10 and PD-L1 CPS ≥ 10. This corresponds to ICER values per QALY of $23,657, $23,982, and $25,134. At the prespecified WTP limit, the probabilities of serplulimab with chemotherapy being the preferred intervention option were 74.4%, 61.3%, and 78.1% for the entire patient population, those with PD-L1 1 ≤ CPS < 10, and those with PD-L1 CPS ≥ 10, respectively. The stability of the presented model was confirmed through sensitivity studies.ConclusionsIn conclusion, the combination of Serplulimab and chemotherapy showed excellent cost-effectiveness compared to chemotherapy alone in treating PD-L1-positive patients with ESCC in China.

Anlotinib combined with penpulimab and nab-paclitaxel as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial.

340 Background: Recently, PD-1 blockades combined with dual chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC. However, the safety profile of conventional dual chemotherapy remained unsatisfactory. Therefore, PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) and single chemotherapy regimen might be a promising strategy. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as first-line combination therapy or second-line monotherapy for patients with ESCC in China clinically. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with penpulimab (PD-1 blockade) and nab-paclitaxel as first-line therapy in advanced ESCC. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and treated with anlotinib (12mg, po, d1~14, q3w) and penpulimab (200mg, iv, d1, q3w) plus nab-paclitaxel (220mg/m2, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 30. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and OS. Results: From Jul 2022 to Aug 2023, a total of 23 patients were enrolled, 19 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 14 PR (73.7%), 2 SD (10.5%) and 3 NE (15.8%). Therefore, the preliminary ORR was 73.7% (95%CI: 48.8%-90.9%), DCR was 84.2% (95%CI: 60.4%-96.6%). Median PFS of the 19 patients was not yet reached. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 23 patients with the incidence &gt;20% were leukopenia (30%) and anemia (30%). Common grade ≥3 treatment-emergent adverse events were leukopenia (9%), glutamic-pyruvic transaminase was elevated (4%), glutamic oxaloacetic transaminase increased (4%), hypertension (4%) and diarrhea (4%). Conclusions: The combination of anlotinib plus penpulimab and nab-paclitaxel as first-line therapy for advanced ESCC demonstrated promising efficacy and manageable safety profile. The conclusions needed to be confirmed in subsequent trials.

Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced oesophageal squamous cell carcinoma: a systematic review and economic evaluation.

Recently, several novel programmed cell death protein 1 (PD-1) inhibitors have been approved for second-line treating advanced or metastatic oesophageal squamous cell carcinoma (OSCC), including camrelizumab, nivolumab, pembrolizumab, sintilimab and tislelizumab. However, the optimal treatment regimen remained ambiguous. The purpose of this study was to investigate the efficacy, safety and economy of available PD-1 inhibitors to determine the optimal treatment from the Chinese healthcare system perspective. A systematic review and economic evaluation. A systematic review was undertaken utilizing PubMed, Web of Science, Cochrane Library, Embase and Scopus databases to identify eligible studies until 31 August 2023. Primary outcomes were progression-free survival (PFS), overall survival (OS) and adverse events (AEs). We also developed a partitioned survival model at 3-week intervals based on five clinical trials to predict long-term costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios for various treatment options. Direct medical costs and utility values were obtained from public drug bidding databases, clinical trials or published literature. The parameter uncertainties within the model were determined via one-way and probabilistic sensitivity analyses. Five randomized controlled trials involving 2837 patients were included in the analysis. Compared with other treatments examined, camrelizumab provided the best PFS benefits [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.56-0.86], and pembrolizumab provided the best OS benefits (HR: 0.55, 95% CI: 0.37-0.82). Nivolumab caused a relatively lower incidence of treatment-related AEs (HR: 0.10, 95% CI: 0.05-0.20) and grade 3-5 AEs (HR: 0.13, 95% CI: 0.08-0.21) than other immunotherapy regimens. In the economic evaluation, average 10-year costs ranged from $5,433.86 (chemotherapy) to $50,617.95 (nivolumab) and mean QALYs ranged from 0.55 (chemotherapy) to 0.82 (camrelizumab). Pembrolizumab was eliminated because of dominance. Of the remaining strategies, when the willingness-to-pay thresholds were 1, 2 and 3 times GDP per capita in 2022, sintilimab, tislelizumab and camrelizumab were the most cost-effective treatment options, respectively. Sintilimab might be the optimal treatment alternative for second-line therapy of advanced OSCC in China, followed by tislelizumab and camrelizumab. This study has been registered on the PROSPERO database with the registration number CRD42023495204.

Economic evaluation of serplulimab plus chemotherapy as the first-line treatment of oesophageal squamous cell carcinoma in China

ObjectiveThe ASTRUM-007 study confirmed the significant efficacy and safety of serplulimab plus chemotherapy for patients with locally advanced/metastatic, programmed cell death-ligand 1 positive oesophageal squamous cell carcinoma (OSCC). The economics...

Overview of Risk Factors for Esophageal Squamous Cell Carcinoma in China

(1) Background: China has the highest esophageal squamous cell carcinoma (ESCC) incidence areas in the world, with some areas of incidence over 100 per 100,000. Despite extensive public health efforts, its etiology is still poorly understood. This study aims to review and summarize past research into potential etiologic factors for ESCC in China. (2) Methods: Relevant observational and intervention studies were systematically extracted from four databases using key terms, reviewed using Rayyan software, and summarized into Excel tables. (3) Results: Among the 207 studies included in this review, 129 studies were focused on genetic etiologic factors, followed by 22 studies focused on dietary-related factors, 19 studies focused on HPV-related factors, and 37 studies focused on other factors. (4) Conclusions: ESCC in China involves a variety of factors including genetic variations, gene–environment interactions, dietary factors like alcohol, tobacco use, pickled vegetables, and salted meat, dietary behavior such as hot food/drink consumption, infections like HPV, poor oral health, gastric atrophy, and socioeconomic factors. Public health measures should prioritize genetic screening for relevant polymorphisms, conduct comprehensive investigations into environmental, dietary, and HPV influences, enhance oral health education, and consider socioeconomic factors overall as integral strategies to reduce ESCC in high-risk areas of China.

Updated results of anlotinib combined with TQB2450 (PD-L1 blockade) as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, multicenter, open-label phase Ⅱ clinical trial.

4041 Background: PD-1 blockades combined with chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC recently. However, the safety profile of conventional chemotherapy was still disappointing. Therefore, the chemotherapy-free regimen might be a promising strategy. As a novel multitarget TKI mainly targeting VEGFR1-3, anlotinib was a potential first-line combination therapy and second-line monotherapy for patients with ESCC in China. TQB2450 was a novel PD-L1 blockade developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Nanjing, China). Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with TQB2450 as first-line therapy in advanced ESCC. The preliminary results were reported in 2023 ASCO-GI Symposium (Abs 377) and the update results were reported here. Methods: Patients with previously untreated metastatic or locally advanced ESCC, whose age was between 18 and 75 years, with ECOG PS of 0 or 1 and life expectancy of &gt; 3 months were eligible as the inclusion criteria. Eligible patients were administered with anlotinib (12mg, po, d1~14, q3w) plus TQB2450 (1200mg, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 and iRECIST using CT scans every 2 cycles for the first 6 cycles, and every 3 cycles thereafter. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 46. The primary endpoint was ORR. Secondary endpoints included safety, PFS, DCR, DoR and OS. Results: From Mar 2022 to Sep 2022, a total of 46 patients were enrolled. At the data cut-off date (Dec, 2022), there were 1 CR (2.2%), 27 PR (58.7%), 14 SD (30.4%) and 4 NE (8.7%). Therefore, the preliminary ORR was 60.9% (95%CI: 45.4%~74.9%), DCR was 91.3% (95%CI: 79.2%~97.6%). The median PFS of the 46 pts was not yet available. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-related adverse events in 46 patients with the incidence &gt; 10% were hypertension (28%), hypothyroidism (20%), leukocytosis (20%), hyperthyroidism (17%), anemia (15%), fatigue (15%), neutrophil count decreased (11%), constipation (11%), sinus bradycardia (11%) and hand-foot syndrome (11%). The common grade ≥3 treatment-related adverse events were hypertension (4%), hand-foot syndrome (2%), hyponatremia (2%), platelet count decreased (2%) and lymphocyte count decreased (2%). Conclusions: Preliminary results suggested that anlotinib combined with TQB2450 as first-line therapy in advanced ESCC exhibited encouraging efficacy and manageable adverse events. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: NCT05038813 .

Cost-effectiveness of camrelizumab plus chemotherapy versus chemotherapy alone as first-line therapy in advanced or metastatic esophageal squamous cell carcinoma

ABSTRACT Objective Camrelizumab combination therapy for advanced or metastatic esophageal squamous cell carcinoma (ESCC) has considerable survival benefits. This study investigated the cost-effectiveness of camrelizumab combination therapy versus chemotherapy alone as a first-line treatment for patients with ESCC from the perspective of the Chinese healthcare system. Methods A three-state partitioned survival model was developed to estimate total costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) over a 20-year time horizon. Sensitivity and scenario analyses were also performed. Results Camrelizumab plus chemotherapy increased QALYs by 0.30 (0.43 LYs), with an incremental cost of $9,272. The ICERs for camrelizumab plus chemotherapy vs chemotherapy alone was $31,062/QALY ($21,599/LY), and the INHB was 0.05 QALY at the cost-effective threshold of $37,653/QALY (3 times China’s GDP per capita). One-way sensitivity analyses showed that the ICER was the most sensitive to utility values in the PFS state. Probabilistic sensitivity analyses suggested that camrelizumab combination therapy had a probability of 74.04% cost-effectiveness at a threshold of $37,653/QALY. Scenario analyses confirmed that the findings were robust. Conclusions Camrelizumab combination therapy is likely to have a cost-effectiveness advantage over chemotherapy alone for previously untreated advanced or metastatic ESCC in China.

Microbial and epidemiological factors in early detection of esophageal squamous cell carcinoma and precancerous lesions.

Microbial and epidemiological factors in early detection of esophageal squamous cell carcinoma and precancerous lesions.

Cost-effectiveness analysis of PD-1 inhibitors combined with chemotherapy as first-line therapy for advanced esophageal squamous-cell carcinoma in China.

Objective: This study was aimed to investigate the cost-effectiveness of all available programmed death 1 (PD-1) inhibitors combined with chemotherapy in the first-line treatment of advanced esophageal squamous-cell carcinoma (ESCC) from the Chinese healthcare system perspective. Methods: A partitioned survival model with a 3-week cycle and a 10-year time horizon was constructed based on a network meta-analysis. The survival data and utility values were derived from clinical trials, and the direct medical costs were collected from public drug bidding database and published literature. Total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. Scenario, one-way and probabilistic sensitivity analyses were performed to assess the uncertainty around model parameters. Results: Compared with mono-chemotherapy, toripalimab, sintilimab and camrelizumab plus chemotherapy were cost-effective treatment regimens, while serplulimab, pembrolizumab and nivolumab plus chemotherapy were not cost-effective options. Toripalimab plus chemotherapy provided the highest QALYs of 0.95 with the lower cost of $8,110.53 compared to other competing alternatives. The robustness of the base-case results was confirmed by scenario and one-way sensitivity analysis. At a willingness-to-pay threshold of three times per capita gross domestic product ($38,351.20) in 2021, the probability of toripalimab plus chemotherapy being the optimal option was 74.25% compared with other six competing alternatives. Conclusion: Toripalimab plus chemotherapy represented the most cost-effective option as the first-line therapy for advanced ESCC patients in China.

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma.

Toripalimab is an immune checkpoint inhibitor (ICI) against programmed death ligand 1 (PD-L1). It has been approved for advanced esophageal squamous cell carcinoma (ESCC) as the first-line treatment due to significantly improved progression-free survival (PFS) and overall survival (OS) in the JUPITER-06 trial. This study aimed to compare the cost-effectiveness between toripalimab plus chemotherapy and placebo plus chemotherapy from the perspective of the Chinese health system. The study developed a 3-year partitioned survival model to assess costs and outcomes in two treatment groups with or without toripalimab. The critical indicator was the incremental cost-effectiveness ratio (ICER). Scenario and sensitivity analyses were performed to evaluate the robustness of the findings and identify the parameters with the greatest impact on cost-effectiveness. In the base case analysis, the incremental effectiveness and cost of toripalimab plus chemotherapy versus placebo plus chemotherapy were 0.26 quality-adjusted life year (QALYs) and $11,254.84, respectively, resulting in an ICER of $43,405.09/QALY, higher than the 2021 willingness-to-pay threshold in China ($37,658.70/QALY). The results were sensitive to the utility of PFS, the incidence of neutropenia in the toripalimab group, and the cost of toripalimab. The toripalimab plus chemotherapy group was cost-effective only if the price of toripalimab decreased by more than 40%. Adding toripalimab to chemotherapy was not cost-effective in patients with advanced ESCC in China.

Anlotinib combined with paclitaxel and cisplatin as neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC).

409 Background: Preoperative chemoradiotherapy before esophagectomy in esophageal squamous cell carcinoma (ESCC) can obtain significant survival benefits for patients compared with surgery alone. The antiangiogenic drugs have shown efficacy in many cancers including esophageal cancer. The benefits of antiangiogenic drugs in neoadjuvant therapy for ESCC still worth exploring. Anlotinib was an effective second-line monotherapy for ESCC in China and the combination of anlotinib and chemotherapy might be a promising strategy as neoadjuvant treatment. Methods: This was a single-arm, non-interventional study. Patients diagnosed stage II-III ESCC confirmed by histopathology would be enrolled(N=30). Patients received neoadjuvant therapy with anlotinib (12 mg, po, d1-14, 21 days per cycle) combined with paclitaxel (135 mg/m2 iv d1, 21 days per cycle) and cisplatin (60-75mg/m2 iv d1, 21 days per cycle). The primary endpoints were pathologic complete response (pCR) rate, rate of R0 resection and disease-free survival (DFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety profile. Results: From July 2020 to September 2022, 20 pts (15 males and 5 females) were enrolled with a median age of 66 years (range: 48-75). 12 pts (60%) had ECOG PS 1, 8 pts had ECOG PS 2. 17/1/2 pts received 2/3/4 cycles of neoadjuvant treatment respectively. In best overall response assessment, ORR was 95% and DCR was 100%. Among them 18 pts underwent esophagectomy and all of them obtained R0 resection, as the rate of R0 resection was 90%. 6 pts (30%) were confirmed to be pCR. The median DFS was not yet available. The safety profile suggested that 3 (15%) pts occurred grade 1-2 treatment-related adverse events (TRAEs), including decreased leukocyte count (5%), diarrhea (5%), nausea and vomiting (5%). No grade ≥3 TRAEs were observed. Conclusions: The preliminary results of this study show promising efficacy and safety of anlotinib combined with paclitaxel and cisplatin as neoadjuvant therapy for patients with esophageal squamous cell carcinoma. More ESCC patients would be recruited in the future. Clinical trial information: ChiCTR2100054374 .

SHR-1701 plus chemotherapy as first-line treatment for unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

363 Background: Platinum-based chemotherapy is the standard first-line treatment for advanced or metastatic ESCC. Recently, the combination of PD-(L)1 pathway blockade with chemotherapy has shown synergistic efficacy in a few clinical trials. SHR-1701 is a novel bifunctional fusion protein composed of a mAb against PD-L1 fused with the extracellular domain of TGF-β receptor II. The purpose of this ongoing phase II trial (ChiCTR2000039909) was to evaluate the efficacy and safety of SHR-1701 combined with chemotherapy for unresectable locally advanced, recurrent or metastatic ESCC in China. Methods: This trial enrolled systemic treatment-naive patients(pts) with histologically or cytologically confirmed unresectable locally advanced, recurrent or metastatic ESCC who had ECOG PS of 0-1. Eligible pts received SHR-1701 (30mg/kg, iv, d1, q3w) combined with up to 6 cycles of albumin-bound paclitaxel (125mg/m2, iv, d1, d8, q3w) and cisplatin (75mg/m2, iv, d1, q3w). For those without progressive disease, maintenance treatment was administrated with SHR-1701 monotherapy until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR), safety and biomarkers. Results: As of September 21, 2022, 18 pts were enrolled. The median age was 67.5 years (range: 46–75 years) and 16 (88.9%) were male. 10 of the pts (55.6%) presented with distant metastasis. 14 pts were included in the efficacy analysis and 17 were in the safety analysis. The ORR and DCR were 85.7% and 100.0%, respectively. One patient achieved a complete response (CR) which will reach confirmation at next visit. 11 pts had partial response (PR), including 9 confirmed PR, one pending confirmation PR, and one unconfirmed PR. In addition, one PR patient got a CR target lesion. Grade 3-4 treatment-related adverse events (AEs) were observed in 23.5% of pts, including neutropenia (11.8%), leukopenia (5.9%), anemia (5.9%), emesis (5.9%) and rash (5.9%). Immune-related AEs (irAEs) were observed in 52.9%, and only one grade 3 irAE of rash occurred. Conclusions: SHR-1701 plus chemotherapy showed potential clinical benefits with acceptable toxicity as first-line treatment, and it might be a favorable option for pts with advanced ESCC. Clinical trial information: ChiCTR2000039909 .

Penpulimab plus chemotherapy with or without anlotinib as first-line treatment for patients with advanced esophageal squamous cell carcinoma (ANSWER): A randomized, two-arm, clinical trial in progress.

TPS482 Background: For patients with advanced esophageal squamous cell carcinoma (ESCC), the combination of immune checkpoint inhibitors with chemotherapy has demonstrated synergistic antitumor activity and manageable safety profile. Anti-angiogenic targeted drugs for ESCC patients are still being explored. Penpulimab is a humanized high-affinity IgG1 anti-programmed cell death 1 (PD-1) monoclonal antibody engineered to completely eliminate Fcγ receptor binding and Fc-mediated effector functions that can compromise antitumor activity. Anlotinib, an oral small molecule tyrosine kinases inhibitor, targeting VEGFR 1/2/3, FGFR 1-4, PDGFR α/β and c-kit, have been recommended by the guidelines for advanced ESCC in China because of its good efficacy and tolerance. The purpose of the study was to investigate the efficacy and safety of penpulimab plus chemotherapy with or without anlotinib as first-line treatment for patients with advanced ESCC. Methods: This is a multi-center, two-arm, phase II study which enrolled patients with advanced ESCC. Eligible patients are aged 18-75 years, ECOG performance status 0~1. Approximately 100 patients will be randomly assigned 1:1 to induction with penpulimab (200mg, iv, d1, q3w) plus chemotherapy (TP: cisplatin [60-75mg/m2, iv, d1-d3, q3w] plus paclitaxel [135-175mg/m2, iv, d1, q3w] or albumin-bound paclitaxel [200-260mg/m2, iv, d1, q3w]) for 4-6 cycles followed by consolidation with penpulimab (200mg, iv, d1, q3w) (arm 1) or induction with penpulimab (200mg, iv, d1, q3w) plus anlotinib (10mg/d [&lt;60kg] / 12mg/d [≥60kg], p.o., d1~14, q3w) plus chemotherapy (TP: cisplatin [60-75mg/m2, iv, d1-d3, q3w] plus paclitaxel [135-175mg/m2, iv, d1, q3w] or albumin-bound paclitaxel [200-260mg/m2, iv, d1, q3w]) for 4-6 cycles followed by consolidation with penpulimab (200mg, iv, d1, q3w) and anlotinib (10mg/d [&lt;60kg)/12mg/d [≥60kg], p.o., d1~14, q3w) (arm 2). Randomization will be stratified by gender (male or female), age (&lt;65, &gt;65), PD-L1 combined positive score (CPS; &lt;1, ≥1, ≥5, ≥10), metastatic site, history of surgery and disease. Patients in arm 1 were treated with second-line anlotinib combined with penpulimab after progression until further disease progression. Patients in arm 2 will continue treated with first-line anlotinib combined with penpulimab until disease progression. Tumor imaging assessment will be performed q6w for 1-6 cycle and q9w thereafter. The primary endpoint was objective response rate (per RECIST v1.1 assessed by investigator). Secondary endpoints included disease control rate, progression-free survival (per RECIST v1.1 assessed by investigator), overall survival, safety and quality of life score. Enrollment in this trial is ongoing. Clinical trial information: NCT05214222 .