Advanced Esophageal Cancer Research Articles

Radiotherapy improved the efficacy of immunotherapy for advanced esophageal cancer.

e16063 Background: The development of immunotherapy has changed treatment methods for advanced esophageal cancer (EC).However, the efficacy of ICIs in advanced EC is not ideal, and the clinical research on the combination of ICIs and Radiotherapy(RT) in advanced EC remains insufficient. This study aimed to evaluate the effectiveness and safety of radiation in first-line immunotherapy for advanced EC. Methods: We conducted 201 advanced EC patients who received first-line ICIs in West China Hospital. The enrolled patients were divided into 2 groups based on whether they received radiation therapy. Results: The analysis included data from 201 patients. The radiotherapy (RT) group had 103 patients (51.2%), whereas the non-radiotherapy (NRT) group included 98 individuals (48.8%). The RT sites include esophagus lesions (83, 80.6%), metastatic lymph nodes (11, 10.7%), liver metastases (4, 3.9%), bone metastases (2, 1.9%), brain metastases (2, 1.9%), lung metastases(1, 0.97%). The median radiation dose was 50.4 Gy (range, 12-68). The RT group had a median OS of 22.8 months (95% CI, 17.8-NA), which was longer than the NRT group's 14.6 months (95% CI, 12.8-26.5) (p = 0.038). And the median PFS was 12.9 months (95% CI, 11.2-14.0) in the RT group versus 7.3 months (95% CI, 6.3-9.7) in the NRT group (p = 0.006). Patients in the RT group had a higher disease control rate (DCR) (99.0% vs. 76.5%, P < 0.001). However, a higher proportion of patients in the RT group developed grade 3-4 myelosuppression (37.86% V.S. 20.20%, P = 0.006), and there was no significant difference in the other AEs. Conclusions: In the first-line immunotherapy for advanced esophageal cancer, radiotherapy has been attributed to improved survival with tolerable toxicity.

Impact of the gut microbiome on response and toxicity to chemotherapy in advanced esophageal cancer

ObjectiveTo identify the gut bacteria associated with chemotherapeutic outcomes, t characterized the gut microbiota in patients with esophageal squamous cell carcinoma (ESCC) in this prospective study. DesignThirty-one patients with ESCC were enrolled. Chemotherapy was performed with paclitaxel and cisplatin (TP). Fecal samples were collected before and after treatment and analyzed using 16S rRNA sequencing. ResultsThe species with differences in baseline abundance between partial response (PR) and non-PR groups was identified as Bacteroides plebeius (P = 0.043). The baseline abundance of B. plebeius was higher in the responder (R, PR + stable disease (SD)) group (P = 0.045) than in the non-responder (NR). The abundance of B. ovatus was identified as a predictor for distinguishing patients with PR from those without PR (sensitivity, 83.3 %; specificity, 69.6 %). The abundance of B. plebeius was positively associated with the response to PR + SD (R) in predicting responders in the receiver operating characteristic (ROC) curve analysis (area under the ROC curve = 0.865, P = 0.041). The abundance of B. plebeius and B.uniform was a predictor of grade (G) 3–4 chemotherapy toxicities. The sensitivity and specificity of the established multi-analyte microbial predictive model demonstrated a better predictive ability than a single parameter (B. uniform or B. plebeius). ConclusionThe abundance of gut microbiota B. plebeius and B. ovatus are associated with the efficacy of TP chemotherapy in patients with ESCC. The abundance of B. plebeius and B.uniform may related to the toxicity of TP chemotherapy.

Safety and efficacy of radiotherapy in combination with immunochemotherapy for advanced esophageal cancer: A retrospective analysis.

e16032 Background: Combining immune checkpoint inhibitors with chemotherapy has emerged as the standard treatment for advanced esophageal cancer. Radiotherapy could alleviate symptoms related to dysphagia. Additionally, it holds the potential to enhance the efficacy of immunotherapy, albeit with an associated risk of increased immunotoxicity. The combination of radiotherapy and immunochemotherapy for advanced esophageal cancer necessitates further investigation into its safety and efficacy. Methods: The medical records of consecutively treated patients with advanced esophageal cancer who underwent immunochemotherapy were retrospectively reviewed. The primary inclusion criteria were as follows: 1. Newly treated, imaging-confirmed stage IV esophageal carcinoma; 2. Radiotherapy administered within 6 cycles of immunochemotherapy; 3. Irradiation dose ≥ 30 Gy; 4. Target area must encompass esophageal neoplasms. The primary endpoints were overall survival (OS) and safety (RECIST 1.1). OS was defined as the time from initial treatment to the date of death. The secondary endpoint was progression-free survival (PFS), defined as the time from initial treatment to cancer progression or death. Median overall survival (mOS) time and median progression-free survival (mPFS) time were used to evaluate efficacy, while the incidence of adverse events (AEs) (CTCAE 5.0) was used to evaluate safety and feasibility. Kaplan-Meier survival analysis was conducted using SPSS25 software. Results: 122 patients were screened and 40 patients were finally included. The median age was 69. A total of 30 male patients were included. Three cases were stage IVa and 37 cases were stage IVb. Distant metastatic sites in these patients were lung (50%), liver (30%), bone (17.5%) and others. All cases were treated with immunochemotherapy as first-line treatment with median 4 cycles. Immunochemotherapy regimens are based on platinum and all treated with programmed death-1 inhibitors. Twenty-three cases were concurrent radiotherapy in combined with chemoimmunotherapy and 17 cases were sequential. For radiation therapy, the median dose was 50Gy in 25 fractions. The incidence of grade 3 and above AEs was shown in 20(50%) cases. Four (10%) patients showed treatment-related grade 5 toxicity (immune pneumonia, myocarditis, hepatitis and myocarditis complicated with hepatitis) which all occurred within 1-4 months after radiotherapy. With a median follow-up of 22.0 months, 26 (65%) cases experienced tumor progression (loco-regional progression only in 3, systemic progression only in 18, and both loco-regional and systemic progression in 5 patients), while 27 patients (67.5%) died. mOS and mPFS were 18.0 months and 6.2 months, respectively. Conclusions: Radiotherapy combined with immunochemotherapy for advanced esophageal cancer showed potential efficacy but relatively high toxicities.

A phase III trial comparing 5-FU plus cisplatin (CF) versus CF plus docetaxel or radiotherapy as neoadjuvant treatment for locally advanced esophageal cancer: 5-year follow-up from JCOG1109.

4082 Background: Triplet chemotherapy with CF plus docetaxel (DCF) improved survival compared to CF as a neoadjuvant treatment for locally advanced esophageal squamous cell cancer (ESCC) based on the result from JCOG1109 (jRCTs031180202). Here we report results with 5 years minimum follow-up. Methods: Eligible patients (pts) with ESCC of clinical stage IB, II, III (excluding T4) (UICC 7th) from 44 institutions were randomized 1:1:1 to neoadjuvant CF (cisplatin 80 mg/m2 on day1 plus 5-FU 800 mg/m2 on days 1-5 Q3W/2 course), DCF (docetaxel 70 mg/m2 on day 1, cisplatin 70 mg/m2 on day1, plus 5-FU 750 mg/m2 on days 1-5 Q3W/3 course), or CF-RT (cisplatin 75 mg/m2 on day 1 plus 5-FU 1000 mg/m2 on days 1-4 Q4W/2 course, radiation 41.4 Gy/23 fr). Primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), and safety. Differences in OS was assessed in the ITT using the stratified log-rank test. The data cutoff date for the analysis was July 20, 2023. Results: Of 601 pts 199 CF, 202 DCF, and 200 CF-RT were enrolled from December 5, 2012 to July 20, 2018. Among 601 pts, 88.2% were male, median (range) age was 65 (30-75), clinical stage III (nonT4) pts were 62.6%. Median follow-up time (range) was 5.5 years (y) (0-10.6). Median OS in CF, DCF, and CF-RT arm were 5.8 y, 10.2 y, and 8.2 y, and 5-year OS was 51.9%, 65.1%, and 60.2%, respectively (stratified log-rank test: one-sided p = 0.004 for CF vs. DCF and one-sided p = 0.15 for CF vs. CF-RT). By the stratified Cox regression analysis for OS, hazard ratios (HR) [95% CI] with DCF vs. CF was 0.68 [0.51–0.91] and that with CF-RT vs. CF was 0.86 [0.66–1.13]. The HR for OS in exploratory comparison between DCF vs. CF-RT was 0.78 [0.59-1.05]. Median PFS in CF, DCF, and CF-RT arm were 2.7 y, 9.5 y, and 5.8 y, and 5-year PFS was 42.6%, 55.7%, and 53.5%, respectively. In the CF arm, there were initially 4 treatment-related and 15 other deaths, with 1 additional treatment-related and 2 other deaths over two more years. The DCF arm reported 4 and 10 deaths respectively, with 3 additional deaths from other causes. In the CF-RT arm, there were 4 treatment-related and 27 other deaths, followed by 2 more treatment-related and 4 other deaths in the extended period. Conclusions: After 5 years follow-up, neoadjuvant DCF continued to demonstrate clinically meaningful improvements in OS and PFS compared to CF in patients with locally advanced ESCC. Clinical trial information: jRCTs031180202 .

493TiP A phase II study of mFOLFOX6 plus nivolumab as initial therapy for patients with advanced esophageal squamous-cell cancer: FLONTALE trial

493TiP A phase II study of mFOLFOX6 plus nivolumab as initial therapy for patients with advanced esophageal squamous-cell cancer: FLONTALE trial

425P Updated results of induction FOLFOX prior to CROSS chemoradiotherapy and surgery in patients with locally advanced esophageal and gastroesophageal junction cancer: A phase II study

425P Updated results of induction FOLFOX prior to CROSS chemoradiotherapy and surgery in patients with locally advanced esophageal and gastroesophageal junction cancer: A phase II study

Interplay of cachexia progression on the efficacy and toxicity of immune checkpoint inhibitors in patients with esophageal squamous cell cancer (ESCC): A longitudinal perspective.

e14629 Background: Immune checkpoint inhibitors (ICIs) have significantly improved the survival of patients with advanced esophageal squamous cell cancer (ESCC), however, the benefit of ICIs was limited to a few patients. It is vital to comprehend the factors influencing the response in order to identify patients who might benefit from ICIs. Cachexia, an intricate multifaceted syndrome characterized by the loss of skeletal muscle and substantial weight reduction, might impact on the immune response and efficacy of ICIs in cancer patients. The purpose of this study is to explore the impact of longitudinal dynamics of cachexia on the efficacy and adverse effect of ICIs for advanced ESCC patients. Methods: Advanced ESCC patients received at least two cycles of ICIs were enrolled from 2017 to 2021. The baseline and longitudinal changes of cachexia during ICI treatment were collected. Based on the longitudinal weight changes during ICI treatment, patients exhibiting cachexia at baseline were categorized into "reversible cachexia" and "irreversible cachexia" group, and patients without cachexia at baseline were also divided into "latent cachexia" and "cachexia-free" group. Kaplan-Meier curves and Cox regression analysis were performed to explore the impact of cachexia on the efficacy ICIs for ESCC patients. And chi-square test was used to evaluate the correlation between cachexia and immune-related adverse effects (irAEs). Results: A total of 278 individuals who had either received or were presently undergoing ICI treatment were enrolled, with the median progression free survival (PFS) of 5.8 months and overall survival (OS) of 8.3 months. Patients with cachexia before treatment had notably poorer outcomes, with median PFS of 7.9 vs 5.3 months (P=0.001), median time to progression (TTP) of 10.9 vs 6.1 months (P<0.001), and median OS of 14.3 vs 9.2 months (P=0.001). In terms of the longitudinal dynamics of cachexia, significantly inferior outcomes were observed for patients in irreversible cachexia compared to reversible cachexia, with the PFS of 4.4 months and 9 months (P<0.001), the TTP of 4.9 months and 9 months (P=0.006), and the OS of 7.8 months and 15 months, respectively (P=0.003). Although patients in latent cachexia group had inferior survival compared to cachexia-free group, no statistical difference was observed, with the PFS of 10.0 and 7.9 months and OS of 13.9 and 16.2 months. Besides, neither baseline nor longitudinal changes of cachexia was associated with irAEs for ESCC patients. Conclusions: This study indicated the impact of baseline and longitudinal cachexia on the efficacy of ICIs for advanced ESCC patients with ICIs. Dynamic monitoring and management of cachexia was recommended during the ICI treatment of ESCC patients.

Efficacy and safety of immunotherapy in patients with liver metastases in patients with esophageal cancer: A retrospective, real-world study.

e16033 Background: Advanced or metastatic esophageal cancer patients tend to have a poor prognosis. The liver is the most common organ of distant metastasis in esophageal cancer. The liver metastases associated with a higher risk of survival. Developing the optimal treatment modalities is especially important for those patients. The efficacy of programmed cell death protein 1 (PD-1) or its ligand (PD-L1) inhibitors have not been clearly clarified in liver metastasis of esophageal cancer. Methods: This is a single-center, retrospective, real-world study. We collected general information and clinical data from patients with liver metastasis of esophageal cancer who admitted to Luoyang Central Hospital between April 2020 and October 2023. All patients were first diagnosed esophageal cancer with liver metastasis and received PD-1 or PD-L1 inhibitor regimen or chemotherapy regimen for the first time. Patients treated with interventional therapy or who had received PD-1 or PD-L1 inhibitors were excluded. The efficacy and safety of patients receiving immunotherapy were evaluated, including overall survival (OS), objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), grade 3-5 treatment-related adverse events (TRAE), and immune-related adverse events (irAE). We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 61 patients with a median age of 61 (44-88) years, 63.9% males; 37 in the immunotherapy group (23 in the first-line group, 62.2%) and 24 in the chemotherapy group (19 in the first-line group, 79.2%). Median OS was 14.1 (95% CI 11.4-16.8) months in the immunotherapy group and 9.2 (95% CI 8.5-9.9, p < 0.01) months in the chemotherapy group; In first-line treatment, the median OS in the two groups was 19.4 (95%CI 15.0-22.2) months and 9.6 (95%CI 8.9-10.3, p < 0.01) months. In all patients, Median PFS was 7.2 (95% CI 6.4 – 8.0) months in the immunotherapy group and 4.6 (95% CI 3.8 – 5.4) months in the chemotherapy group, p = 0.174. The ORR of immunotherapy and chemotherapy was 56.8% and 33.3%; DCR was 78.4% and 62.5%. Univariate and multivariate analysis showed that N stage and treatment regimen were significant factors related with OS. Grade 3 TRAE in immunotherapy group and chemotherapy group were 29.7% and 29.2%, respectively. The incidence of irAEs was 10.8%. No treatment-related deaths occurred. Conclusions: This real-world data showed PD-1 or PD-L1 inhibitors might have good efficacy and manageable safety in EC patients with liver metastases, especially in first-line patients. [Table: see text]

9MW2821, a nectin-4 antibody-drug conjugate (ADC), in patients with advanced solid tumor: Results from a phase 1/2a study.

3013 Background: 9MW2821 is a monoclonal ADC that delivers monomethyl auristatin E to cells expressing Nectin-4. Nectin-4 is an adhesion molecule that highly expressed in variety of solid tumors, especially urothelial cancer (UC), cervical cancer (CC), esophageal cancer (EC) and breast cancer. Here we report the updated safety and efficacy data of 9MW2821. Methods: 9MW2821 was administered by intravenous infusion at doses of 0.33-1.5mg/kg on days 1, 8 and 15 of each 28-day cycle. The study included dose escalation, dose expansion and cohort expansion period which included UC, CC, EC, triple negative breast cancer (TNBC) and other Nectin-4 positive solid tumors that progressed after ≥1 systemic treatments (Tx). Primary objectives were assessment of safety and preliminary efficacy. Results: As of Jan 15, 2024, 260 patients (pts) were enrolled with doses ranging from 0.33 to 1.5mg/kg. Only 1 out of 6 pts in 1.5mg/kg group had dose limiting toxicity (grade 4 neutropenia lasted more than 5 days). The maximum tolerated dose was not reached up to 1.5mg/kg and the RP2D was selected as 1.25mg/kg for tolerance. 240 pts were enrolled at dose of 1.25mg/kg. The most common TRAEs of 1.25mg/kg dose group (≥20%, all grade/≥5%, ≥G3) were white blood cell (WBC) count decreased (50.8%, 23.3%), neutrophil count decreased (46.3%, 27.9%), anemia (43.8%, 8.3%), aspartate aminotransferase increased (42.1%, 2.9%), alanine aminotransferase increased (35.4%, 2.1%), asthenia (32.1%, 2.9%), rash (30.0%, 5.0%), decreased appetite (28.8%, 1.3%), nausea (26.7%, 0%), hyperglycemia (25.4%, 2.1%), platelet count decreased (24.2%, 4.6%), alopecia (24.2%, 0%), hypoaesthesia (22.5%, 1.7%), constipation (21.3%, 0%), vomiting (20.9%, 1.3%), hypertriglyceridemia (20.4%, 2.1%), gamma-glutamyltransferase increased (15.8%, 5.4%). Among 190 pts treated with 9MW2821 at 1.25mg/kg or above and reached tumor assessment, objective response rate (ORR) and disease control rate (DCR) was 35.3% and 78.4%, respectively. 37 UC pts, 45 CC pts, 27 EC pts and 16 TNBC pts were enrolled at 1.25mg/kg and evaluable for tumor assessment. Median prior lines of Tx were 2 (range, 1-4). All UC, 51% CC and 93% EC pts progressed after platinum-based chemotherapy and immune checkpoint inhibitors, respectively. Objective responses were also observed in pts with other solid tumor types. Conclusions: The data indicated encouraging efficacy of 9MW2821 in advanced UC, CC, EC and TNBC. 9MW2821 is the first Nectin-4 targeting ADC showed antitumor activity in patients with CC, EC and TNBC. The safety profile showed adequate tolerability. Clinical trial information: NCT05216965 . [Table: see text]

401P Vibostolimab coformulated with pembrolizumab (vibo/pembro) + chemotherapy (chemo) as first-line treatment for advanced esophageal cancer (ec): Results from cohort E of the phase II KEYVIBE-005 study

401P Vibostolimab coformulated with pembrolizumab (vibo/pembro) + chemotherapy (chemo) as first-line treatment for advanced esophageal cancer (ec): Results from cohort E of the phase II KEYVIBE-005 study

A single-arm, open-label phase II clinical trial of SHR-1210 (camrelizumab) in combination with nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma.

e16007 Background: The prognosis of advanced esophageal cancer is bleak, and the current first-line regimen based on paclitaxel, cisplatin and fluorouracil (TPF) with an effective rate is about 30%. The second-line treatment regimen based on anti-PD-1/PD-L1 monoclonal antibodies obtained median overall survival (mOS) 10.8 months in phase I-II clinical trials, but a large proportion of patients (pts) still do not respond to this therapy. Additionally, nimotuzumab in the previous Cuba phase 2 study had a good disease control rate (DCR) combined with PF regimen. So, we conducted the study to evaluate the new combination modality efficacy and treatment-related adverse events (safety). The primary endpoints was ORR, and the secondary endpoints included overall survival (OS), DCR, progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the second-line treatment for ORR is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha=0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached CR/PR. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase 2 study, a total of 41 pts were administered. One case was lost to follow-up. The mean age was 45 years (range, 42-77). The results of the intention-to-treat analysis showed that the ORR was 36% (15/42). The mOS was 12.62 months with median follow-up 8.28 months. The 9-month and 12-month survival rates were 84% and 51%, respectively. The DCR was 81% (34/42). Median PFS was 9.89 months with median follow-up 9.17 months. In terms of safety, the incidence of TEAEs was 60% (25/42), of which 71% (30/42) had adverse events below grade 3 and 26% (11/42) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 10% (4/42), of which 0 case related to nimotuzumab and 4 cases related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma showed a trend benefit for ORR and OS with a controllable toxicity.

Prediction for major pathologic response after neoadjuvant tislelizumab combined with chemotherapy in patients with locally advanced esophageal squamous cell carcinoma by RNA sequencing: A single-arm, phase II trial.

4078 Background: Although neoadjuvant chemoradiotherapy is evolved into standard-of-care treatment in locally advanced esophageal cancer (EC) patients (pts), nearly half of pts experience relapse and death within 5 years. It is therefore important to establish novel and effective treatment strategies for further improve survival. With successful treatment of unresectable esophageal squamous cell carcinoma (ESCC) with PD-1/PD-L1 inhibitors, which are expected to provide better benefits in resectable ESCC preoperatively. However, owing to lack effective predictors in MPR in neoadjuvant immunotherapy, efficacy of treatment is unsatisfactory. In this study we sought to explore potential biomarkers in treatment of locally advanced ESCC with tislelizumab combined with chemotherapy preoperatively. Methods: In this single centre, perspective, single arm study, 62 locally advanced (stage II-IVA) ESCC pts were enrolled from January 2023 to December. Pts received tislelizumab (200mg/ d1 Q3W) and chemotherapy (Albumin Paclitaxel 240 mg/m2, Carboplatin: AUC=5 Q3W, d1 or Nedaplatin: 70mg d1 Q3W). Minimally invasive esophagectomy was performed within 4-6 weeks after preoperative therapy. The primary endpoint was MPR rate and secondary endpoints were R0 resection rates and adverse events (AEs). Exploratory biomarker analysis was performed on tumor biopsy before neoadjuvant therapy. Results: 62 pts were enrolled who received all cycles of tislelizumab plus chemotherapy and 84% (52/62) of whom proceeded to surgery. Grade I AEs were observed in 57 (91.3%) pts and most common of which was anemia (49/62, 79%). 19 (30.6%) pts had grade II and 4 (6.4%) had grade III AEs. No higher AEs was observed. Reasons for not undergoing surgery was patient refusal (10/62, 16.1%). No perioperative death was observed. MPR, pCR and R0 resection rate were (55.8%), (23.1%) and (100%), respectively. The mediate follow-up time was 7.4 (1.7-12.6) months and no relapse was found before the last follow-up.10 pts underwent RNA-sequencing, of which 5 achieved MPR and 5 were not. Compared to MPR pts, 393 upregulated and 1950 downregulated genes were found in non-MPR patients. Additionally, it was indicated that immunomodulatory, keratinocyte differentiation and calcium signaling pathway may correlate with MPR status by GSEA, GO and KEGG analysis. Moreover, some hub genes, such as IL6, MMP1, SPPR3, CRNN, were identified to be associate with non-MPR after neoadjuvant therapy. Conclusions: Our results indicated that tislelizumab combined with chemotherapy is a feasibility and effective neoadjuvant treatment option for locally advanced ESCC. In addition, some hub genes were found to be associated with non-MPR after neoadjuvant therapy. Further experimental studies are needed to investigate these findings. Clinical trial information: NCT05880082 .

Immune checkpoint inhibitor retreatment in second-line treatment of esophageal cancer: A real-world study.

e16034 Background: Immunotherapy combined with chemotherapy has been recommended in several guidelines and consensus for the first-line treatment of advanced esophageal cancer(EC), but it is controversial whether to continue immune checkpoint inhibitors (ICIs) after the progress of first-line immunotherapy. Methods: This was a single-center, retrospective, observational, real-world study to collect general conditions and clinical data of EC patients hospitalized in the First Affiliated Hospital of Henan University of Science and Technology between February 2020 and December 2023. All patients received programmed cell death protein 1 (PD-1) or its ligand (PD-L1) inhibitor combination therapy in the first-line and received at least two cycles of PD-1/PD-L1 inhibitor-based therapy in the second-line setting after progression. We evaluated the efficacy and safety including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), grade 3-5 treatment-related adverse effects (TRAE) and immune-related adverse events (irAEs). We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 214 patients, with a median age 67.9 (47 – 87) years, male sex 66.8%, 201(93.9%) ESCC and 11(5.1%) EAC. In all patients, the mOS and mPFS were 9.6 (95%CI 9.1-10.1) months and 4.4 (95%CI 4.1-4.7) months; The ORR was 33.2%, DCR was 65.9%. 162 (75.7%) patients treated with immunochemotherapy(I+C), 37 (17.3%) patients received immunotherapy combined with anti-angiogenic drugs(I+A) and 15 (7.0%) patients treated with immunotherapy combined with chemotherapy and anti-angiogenic drugs(I+C+A). The mOS were 9.1 (95% CI 8.4 – 9.8) months, 10.0 (95% CI 8.7 – 11.3) months and 11.5 (95% CI 10.7 – 12.3) months, respectively. The mPFS were 4.3m (95%CI 4.0-4.6) months, 4.3 (95%CI 4.0-14.6) months and 6.0 (95%CI 4.2-6.4) months. mPFS and mOS did not have significant difference between these groups. Univariate and multivariate analyses showed that PFS more than 6 months on first-line therapy was an independent prognostic factor for PFS and OS in second-line therapy. The incidence of grade ≥ 3 TRAEs and irAEs were 25.7% and 5.6%. No treatment-related deaths occurred. Conclusions: This real-world data showed PD-1 or PD-L1 inhibitors retreatment might have good efficacy and manageable safety in EC patients who progress after first-line immunochemotherapy. [Table: see text]

Efficacy and safety of the combination of tisleizumab with chemoradiotherapy in oligorecurrence esophageal squamous cell carcinoma: A prospective phase II study.

4057 Background: The postoperative recurrence and metastasis rate of esophageal squamous cell carcinoma (ESCC) remains high and prognosis is poor. PD-1 immune checkpoint inhibitors have shown efficacy in targeting advanced esophageal cancer. This phase II study aims to explore the efficacy and safety of concurrent chemoradiotherapy and immunotherapy for ESCC patients with oligometastatic recurrence after radical surgery. Methods: This phase II study enrolled ESCC patients from 3 hospitals in China, diagnosed oligometastatic recurrence after radical surgery. The 1st stage, with 10 patients enrolled, was designed to explore the safety level and the 2nd stage was to explore efficacy. The oligorecurrence is defined as progression occurring three months after the operation with no more than three metastatic regions. The local recurrence was defined as tumor bed or anastomotic recurrence. The regional lymph node recurrences were regarded as mediastinal region and celiac lymph, respectively. The distal recurrences were considered as supraclavicular, retroperitoneal region and other distal organs. All of the positive regional lymph nodes were collectively counted as one lesion if regional lymph node recurrences existed. Tisleizumab was delivered on D1,22. Nab-paclitaxel 150mg/m2 (starting on D2,23) and cisplatin, 75mg/m2(starting on D2-4,22-24) were administered for two cycles. The radiotherapy was delivered with 50.4-60Gy, 1.8-2Gy per fraction. After CRT, patients received Tisleizumab every 3 weeks for 3-6 months and 2-4 cycle consolidation chemotherapy. The primary endpoint was 1-year OS, the second endpoints were 1-year PFS, ORR and toxicities. Results: Between Jan 2021 and May 2023,50 patients were screened for enrolment and 44 patients met the eligibility criteria. The metastatic regions were made up by the local (15.9%),regional (47.7%), distal (13.6%) and mixed recurrence (22.7%). In the 1st stage, one patient had a grade-3 Immune-related erythra out of ten patients. All patients were delivered chemoradiotherapy, 36(81.8%) patients had completed two cycles of immunotherapy. The ORR rate was 84.1%. During concurrent chemoradiotherapy, the incidence of grade≥3 treatment-related adverse events was nausea (9.1%), vomit (4.5%), anorexia (4.5%), leukopenia (13.6%), hepatitis (2.3%), radiation esophagitis (1.4%), erythra (4.5%). There were 5 cases of Immune-related adverse, including 2 cases of erythra, 1 case of hypothyroidism, hepatitis, gastroenteritis, respectively. With the median follow-up time of 19 months (range:4-30 months), 1-year OS and PFS was 83.2% and 79.2%. The median OS and the median PFS were not reached. Conclusions: Concurrent chemoradiotherapy and immunotherapy yielded satisfactory 1-year OS rate and manageable toxicities in oligometastatic recurrence patients with ESCC after radical surgery. Clinical trial information: NCT04821765 .

Analysis of ctDNA assay as a strategy for watchful waiting in locally advanced esophageal cancer.

e16126 Background: Standard treatment for locally advanced esophagogastric (EG) cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. The treatment goal is curative in order to control the tumor in the thorax, prevent regional recurrence, and to help prevent or delay metastatic progression. Despite achieving pathologic complete response (pCR) after surgery, patients with supposed local control may have recurrence up to a third of the time. Circulating tumor DNA (ctDNA) is an evolving tool in the field of oncology used as an informative biomarker. We provide longitudinal, real world observation of ctDNA minimal residual disease (MRD) to predict pCR and risk of recurrence. Methods: 22 participants with newly diagnosed locoregional EG cancer were enrolled under single institution approved protocol [IRB#1864127-7]. CtDNA-based MRD levels were obtained by Natera SignateraTM bespoke mPCR-NGS assay. Additionally, Natera Altera TM was used as a non-invasive biopsy to provide the comprehensive tumor-specific genomic profile. We evaluated thirteen participants who underwent definitive surgery and those who did not. Non-invasive plasma samples were surveilled at various timepoints which included the time of diagnosis, during neoadjuvant CRT, after definitive surgery. The primary outcome is a comparison of assay recurrence (AR) to disease recurrence (DR) defined as radiologic or clinical disease recurrence in participants with locoregional disease. Exploratory endpoints examine the profile of tumor. Results: Baseline levels were detected (n = 22) at new diagnoses. Longitudinal results demonstrated ctDNA clearance in eight participants while undergoing neoadjuvant chemoradiaton. Residual ctDNA were found in five participants for which two had clinical disease recurrence. Esophagectomy was done in three participants achieving pCR. Post procedural ctDNA were detected in one participant. Conclusions: The clearance of ctDNA favors less clinical disease recurrence in this study. This may indicate that ctDNA clearance confers lower risk of relapase. However, a larger cohort prospective study will be needed to validate the application of ctDNA as an early biomarker. The future application of ctDNA can be used to identify patients who may benefit from a watchful waiting adjuvant strategy instead of proceeding with invasive esophagectomy.

Age and body composition of patients receiving treatment for locally advanced esophageal cancer.

e16094 Background: Standard of care for locally advanced esophageal cancer consists of chemoradiation (chemoRT) followed by esophagectomy. Fewer patients in older populations with locally advanced esophageal cancer undergo esophagectomy when compared to their younger counterparts. Furthermore, frail patients frequently forgo surgery after chemoRT. The current study examined the relationship between age, body composition, and treatment decision-making in locally advanced esophageal cancer. Methods: Patients with clinical stage T2-4, N0-2, and M0 adenocarcinoma or squamous cell carcinoma of the mid or distal esophagus diagnosed between 2010-2021 were included from 11 hospitals across our healthcare system. Treatment decision-points included receipt of chemoRT versus non-curative therapy, unresectable disease after chemoRT defined by metastatic disease or upper mediastinal lymphadenopathy, and receipt of surgery stratified by histology. Sociodemographic data including age, race, sex, insurance status, socioeconomic status, body composition data from CT imaging (skeletal muscle gauge [SMG]), and outcome data were collected. Skeletal Muscle Gauge was calculated as the product of skeletal muscle cross-sectional area at L3 normalized for height and muscle density. Fisher's exact test was used for categorical variables and Kruskal-Wallis for continuous variables. Results: 513 patients were included in the analysis, of which 399 (78%) had adenocarcinoma and 114 (22%) had squamous cell carcinoma. Median age was 66. Of the 513 patients, 472 (92%) underwent chemoRT (366 [78%] adenocarcinoma, 106 [22%] squamous cell carcinoma). Patients who were over the age of 75 were less likely to undergo chemoRT when compared to their younger counterparts (85% vs. 94%, p = 0.002). After the completion of chemoRT, 419 (89%) patients were deemed resectable, 330 adenocarcinoma and 89 with squamous cell carcinoma. Among resectable patients with adenocarcinoma, those > 75 years old and lower SMG were less likely to receive surgery (p < 0.001 and p =0.001). Age and body composition associated with lower receipt of surgery in locally advanced esophageal cancer patients was significant on both univariate and multivariate analyses. Conclusions: Patients over 75 are less likely to undergo chemoRT and surgical resection for locally advanced esophageal cancer. Among patients with resectable disease who have completed chemoRT, those with unfavorable body composition as measured by low SMG on CT imaging are also less likely to undergo surgical resection. These measures may be helpful in surgical decision-making in patients with locally-advanced esophageal cancer. Further study is warranted to more precisely define the relationship between age, body composition, and risk of surgery in esophageal cancer.

Social factors in the receipt of treatment for locally advanced esophageal cancer.

e16093 Background: Treatment for locally advanced esophageal cancer consists of chemoradiation (chemoRT) followed by esophagectomy. Studies have suggested Black patients were less likely to undergo surgery for esophageal cancer with inferior survival rates, attributing this to differences in access to surgery. These studies have not always accounted for differences in the natural history of adenocarcinoma and squamous cell carcinoma, which have strong racial correlations and different rates of surgical resection. The current study examined outcomes and patterns of care for patients with locally advanced esophageal cancer, both adenocarcinoma and squamous cell carcinoma, in relation to their sociodemographic characteristics. Methods: Patients with clinical stage T2-4, N0-2, and M0 adenocarcinoma or squamous cell carcinoma of the mid or distal esophagus diagnosed between 2010-2021 were included from 11 hospitals across our healthcare system. Treatment decision-points included receipt of chemoRT, unresectable disease after chemoRT defined by metastatic disease or upper mediastinal lymphadenopathy, and receipt of surgery stratified by histology. Age, race, sex, insurance status, socioeconomic status measured by social deprivation index (SDI), and outcome data were collected. Chi-squared test was used for categorical variables and Kruskal-Wallis for continuous variables. Results: 513 patients were included, of whom 472 patients underwent chemoRT (366 adenocarcinoma, 106 squamous cell). Female patients (n =97) were less likely to undergo chemoRT (84% vs. 94%, p = 0.003). Patients without insurance were less likely to undergo chemoRT (86% vs 93%, p = 0.023). After completing chemoRT, 419 patients (82%) were resectable. Surgery was performed in 262/330 patients (79%) with adenocarcinoma and 38/89 patients (43%) with squamous cell carcinoma, reflecting the differences in natural history by histology. Among 330 patients with resectable adenocarcinoma, higher SDI was associated with a lower rate of surgery, while there was no difference in the receipt of surgery based on sex, race or insurance status. There were no detectable social factors associated with receipt of surgery for squamous cell carcinoma. Conclusions: Within our healthcare system, female and Medicaid/uninsured patients are less likely to undergo chemoRT for locally advanced esophageal cancer. Further studies are needed to evaluate whether sex-specific bias plays a role in the receipt of chemoRT. Among patients with resectable locally advanced esophageal adenocarcinoma treated with chemoRT, those with high SDI are less likely to undergo surgery. Further studies are needed to assess which component factors of socioeconomic status most impact the receipt of surgery so they can be targeted. The previous findings that race impacts treatment of locally advanced esophageal cancer are not seen in our healthcare system when accounting for histology.

411P Time-to-treatment initiation and survival in patients with locally advanced esophageal cancer

411P Time-to-treatment initiation and survival in patients with locally advanced esophageal cancer

Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer.

In the KEYNOTE-590 study, first-line pembrolizumab plus chemotherapy provided statistically significant improvement in overall survival, progression-free survival, and objective response rate compared with chemotherapy, with a manageable safety profile in patients with advanced esophageal cancer. Prespecified health-related quality-of-life (HRQoL) outcomes are reported. Change from baseline to week 18 in the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/QoL (GHS/QoL) and QLQ-Esophageal cancer module (OES18) dysphagia, pain, and reflux scales were evaluated. The HRQoL analysis included 730 patients who received treatment and completed ≥1 HRQoL assessment. Least squares mean (LSM) change from baseline to week 18 was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 reflux scales. The QLQ-OES18 dysphagia (LSM difference, -5.54; 95% CI, -10.93 to -0.16) and pain (LSM difference, -2.94; 95% CI, -5.86 to -0.02) scales favored pembrolizumab plus chemotherapy over placebo plus chemotherapy. Median time to confirmed deterioration (TTD) was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 dysphagia and reflux scales. Compared with chemotherapy, pembrolizumab plus chemotherapy prolonged median TTD, as seen on the QLQ-OES18 pain scale (HR, 0.69; 95% CI, 0.51 to 0.95). The use of pembrolizumab plus chemotherapy maintained HRQoL at week 18 relative to baseline and was comparable with placebo plus chemotherapy. These HRQoL results together with published reports of efficacy, support the use of pembrolizumab plus chemotherapy as first-line therapy for advanced/metastatic esophageal cancer. NCT03189719.

Survival Outcomes of Patients with Esophageal Cancer and Post-chemoradiotherapy Surgical T4b Disease: Is Palliative Resection Justified?

In patients with locally advanced esophageal cancer who had undergone chemoradiotherapy (CRT), the limitations of radiological evaluation may necessitate surgical exploration to ascertain disease resectability. Upon intraoperative confirmation of T4b disease (sT4b), the optimal management strategy remains unclear. While some surgeons may opt against resection, others advocate for palliative esophagectomy (PE). Regrettably, the current literature does not provide a consensus on the most effective approach for managing these intricate cases. The study cohort consisted of 68 patients with esophageal squamous cell carcinoma (ESCC) who presented with sT4b disease following CRT. The perioperative outcomes and overall survival (OS) were compared between patients who underwent PE (n=56) and those who received an open-close (OC) procedure (n=12). Patients who underwent an OC procedure experienced a shorter hospital stay (16.5 vs. 28.8 days; p=0.052) and showed a non-significant reduction in the rate of major complications (33.9% vs. 25%; p=0.549) and in-hospital mortality (0% vs. 5.4%; p=0.412) than those who received PE; however, PE was associated with a superior 2-year OS rate than OC (9.6% vs. 0%; p=0.009). In multivariable analysis, a pretreatment clinical stage of II/III (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.31-0.87; p=0.013) and PE with retrosternal reconstruction (HR 0.38, 95% CI 0.15-0.49; p=0.010) were independently associated with a more favorable OS. PE with retrosternal reconstruction may be a feasible approach for patients with ESCC exhibiting sT4b disease after CRT.