Metastatic Esophageal Squamous Cell Cancer Research Articles

Efficacy and safety of surufatinib, toripalimab, nab-paclitaxel in combination with radiotherapy or surgery in the first-line treatment of esophageal squamous cell cancer: A single-centered prospective clinical trial.

e16047 Background: Chemotherapy(CT) plus immune checkpoint inhibitors (ICIs) has become the current standard of care in the first-line treatment of metastatic esophageal squamous cell cancer(ESCC). In locally advanced setting, radiochemotherapy with or without resection remains the standard of care. Surufatinib, a novel small-molecule kinase inhibitor targeting VEGFR1-3, FGFR and CSF-1R, in combination with PD-1 inhibitors have demonstrated synergistic anti-tumor activities in previous studies. This single-centered prospective clinical trial aims to evaluate the efficacy and safety of surufatinib(SUR), toripalimab(TOR), nab-paclitaxel(NAB) in combination with radiotherapy or surgery in the first-line treatment of locally advanced(LA) or metastatic(R/M) ESCC. Methods: Eligible patients(pts) with confirmed LA or R/M, ECOG PS 0-2 and no prior systematic treatment were enrolled in the trial. Pts would receive 260mg/m2 NAB and TOR 240mg on day 1 and SUR 250mg once daily in each 21-day cycle as induction therapy for two cycles, followed by surgery or another two cycles of concurrent chemoradiotherapy(CCRT) with NAB, SUR and radiotherapy, in which involved-field irradiation were conducted at the dose of 50-63 Gy/25-30F, 1.8-2 Gy per fraction, 5 fractions per week. As maintenance therapy, daily SUR and TOR every three week were administered until disease progression or unacceptable toxicities. Progression-free survival (PFS) was the primary endpoint. Results: As of Jan 7, 2024, 16 pts were enrolled, of whom 15 were evaluable. 14(87.5%) pts were male. The median age was 69.5 (range: 45-79). Tumor located in upper(18.8%), middle(25%) and lower(56.2%) thoracic. 1(6.2%) is Stage II disease, 12(75%) Stage III and 3(18.8%) Stage IV. 8 (50%) pts were with PD-L1 CPS greater than 1, 5 (31.25%) pts greater than 5, and 3 (18.75%) pts greater than 10. PD-L1 CPS of 6(37.50%) pts was unknown. With a median follow-up time of 5 (range: 1-12) months, despite the immatureness of PFS, the 12-month PFS rate was 77.14% (95% CI: 48.89%-100%). The objective response rate was 93.3% (14/15), and disease control rate was 100% (15/15). Five of the included pts met the resection criteria during treatment and underwent subsequent R0 resection. The most common adverse events (≥20%) of all grades were hypoesthesia (62.5%), nausea and vomiting (50%), and white blood cell decrease (43.75%). Conclusions: The combination ofsurufatinib, toripalimab, nab-paclitaxel with radiotherapy or surgery has demonstrated promising efficacy and a well-tolerated safety profile as a potential first-line treatment for LA or R/M ESCC. This ongoing trial merits further investigation and holds significant implications for clinical practice.

Tislelizumab (Tevimbra) for esophageal cancer.

The FDA has approved tislelizumab (Tevimbra – BeiGene), a programmed death receptor-1 (PD-1) blocking antibody, for treatment of unresectable or metastatic esophageal squamous cell cancer in adults who received prior systemic chemotherapy that did not include a programmed death ligand-1 (PD-L1) inhibitor.

Phase II multicenter trial: first-line immunochemotherapy with or without radiotherapy in metastatic esophageal squamous cell cancer (SCR-ESCC-01).

This randomized phase II trial (NCT05978193) combines low-dose radiotherapy (LDRT) and conventionally fractionated radiotherapy (CFRT) with immunochemotherapy for metastatic esophageal squamous cell carcinoma, aiming to assess the potential enhanced effect of radiotherapy on immunotherapy. Patients are administered a PD-1 inhibitor along with paclitaxel and platinum-based chemotherapy (arm B), or combined with LDRT and CFRT (arm A). Immunotherapy is given every 3 weeks with chemotherapy for 4 cycles, followed by immunotherapy maintenance therapy for up to 24months. In arm A, LDRT (2Gy, 2 fractions; delivered to the primary and all metastatic tumors) precedes each immunochemotherapy cycle for 4 cycles, followed by CFRT (40-50Gy, 20-25 fractions; delivered to the primary tumor) starting from the fifth immunotherapy cycle. The primary end point is median progression-free survival. Clinical Trial Registration: NCT05978193 (clinicaltrials.gov).

Local Ablative Treatment Improves Survival in ESCC Patients With Specific Metastases, 2010-2016: A Population-Based SEER Analysis.

BackgroundWe aimed to explore the role of local ablative treatment (LAT) in metastatic esophageal squamous cell cancer (ESCC) patients who received chemotherapy and identify patients who will most likely benefit.MethodsWe analyzed data of metastatic ESCC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The chi-square test was used to evaluate the unadjusted clinicopathological categorical variables between the two groups. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors of overall survival. Propensity score matching (PSM) was used to adjust the differences between the two groups.ResultsOverall, 720 metastatic ESCC patients treated with chemotherapy were analyzed in this study; 63.2% of patients (n = 455) received LAT, including radiotherapy (n = 444), primary site surgery (n = 12), or lymph node dissection (n = 27). Gender (HR = 1.220, 95% CI: 1.024–1.453, p = 0.026), bone metastases (HR = 1.559, 95% CI: 1.292–1.882, p < 0.001), and liver metastases (HR = 1.457, 95% CI: 1.237–1.716, p < 0.001) were independent prognostic factors in the entire population. However, LAT was not an independent prognostic factor. Further subgroup analyses showed that LAT improved OS from 8.0 months to 10.0 months in patients with metastases other than bone/liver (HR = 0.759, 95% CI: 0.600–0.961, p = 0.022). LAT was not a prognostic factor in patients with bone/liver metastases (HR = 0.995, 95% CI: 0.799–1.239, p = 0.961). After PSM, the median OS was 8.0 months (95% CI: 7.2–8.8 months) and patients who received LAT had a better OS than patients without LAT (HR = 0.796, 95% CI: 0.653–0.968, p = 0.023). Patients with metastases other than bone/liver could benefit from LAT compared with those with bone/liver metastases.ConclusionsOur study indicated that metastatic ESCC patients with metastases other than bone/liver could derive additional benefit from LAT with systemic chemotherapy.

Camrelizumab plus Chemotherapy for Metastatic Esophageal Squamous Cell Cancer

The immune checkpoint inhibitor pembrolizumab combined with chemotherapy was recently approved by the FDA for first-line treatment of esophageal and

LBA52 Sintilimab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced or metastatic esophageal squamous cell cancer: First results of the phase III ORIENT-15 study

ORIENT-15 is a global, randomized, double-blind study to evaluate the efficacy and safety of sintilimab + chemo (S+C) vs chemo (C) as first-line (1L) treatment in patients (pts) with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

Cost-Utility Analysis of Continuation Versus Discontinuation of First-Line Chemotherapy in Patients With Metastatic Squamous-Cell Esophageal Cancer: Economic Evaluation Alongside the E-DIS Trial

ObjectivesContinuous chemotherapy has been used to treat patients with metastatic esophageal squamous cell carcinoma (mESCC), despite weak evidence supporting a clinical benefit, associated side effects for the patients, and unjustified medical costs. In the French setting, we conducted a cost-utility analysis alongside the randomized E-DIS trial (NCT01248299), which compared first-line fluorouracil/platinum-based chemotherapy continuation (CT-CONT) to CT discontinuation (CT-DISC) in progressive-free patients after an initial 6-week treatment phase. MethodsA partitioned survival analysis was performed using patient-level data collected during the trial for survival outcomes, quality of life (EQ-5D-3L), and medical costs. The mean quality-adjusted life-years (QALYs) and medical costs were estimated over an 18-month period to assess the incremental net monetary benefit and incremental cost-effectiveness ratio. Uncertainty was handled using the nonparametric bootstrap and univariate analysis. Sixty-seven patients with mESCC were randomized and included in the cost-utility analysis. ResultsOn average, CT-CONT slightly decreased the number of QALYs (-0.038) and increased the cost per patient (+ €1177). At a willingness-to-pay threshold of €50 000/QALY, the incremental net monetary benefit was negative (-€3077 [95% confidence interval: -6564; 4359]), and the incremental cost-effectiveness ratio was -30 958€/QALY (CT-CONT dominated). The probability of the CT-CONT treatment option being cost-effective at a willingness-to-pay threshold of €50 000/QALY, compared to CT-DISC, was 29%. ConclusionsCT-DISC may be considered as an alternative therapeutic option to CT-CONT in patients with mESCC who have stable disease after an initial chemotherapy treatment phase. A continuous chemotherapy could indeed reduce the number of QALYs because of the disutility associated with the continuous treatment.

Efficacy of Radiotherapy In Oligometastatic Esophageal Squamous Cell Cancer Patients: New Evidence From A Retrospective Study

The growing evidence suggests the survival outcomes of radiotherapy (RT) for metastatic esophageal squamous cell cancer (ESCC) patients. Compared to polymetastatic ESCC, oligometastatic ESCC has favorable prognosis due to its indolent property, and was more likely to get clinical benefit from RT. The purpose of the present study was to characterize survival outcomes associated with primary tumor- and metastases- directed RT (MDRT and PTDRT) in newly diagnosed oligometastatic esophageal cancer. Newly diagnosed oligometastatic ESCC patients, defined as the presence of 1-5 metastases and 1-3 lesions, were included in this study. Characteristic of patients were compared with c2 test. Overall survival (OS) and progression-free survival (PFS) after treatment with CT (chemotherapy) alone and CT+RT were compared by using Cox proportional hazards models and survival analysis. Further analysis was performed to compared the efficacy of CT+PTDRT, CT+MDRT or CT+PTDRT+MDRT among patients receiving CT+RT. A total of 239 oligometastatic ESCC patients were enrolled in this study, including 76 patients treated with CT alone and 163 patients treated with CT + RT (CT+PTDRT, n = 28; CT+MDRT, n = 7; CT+PTDRT+MDRT, n = 128). There was no significant difference between the groups with respect to age, sex, ECOG performance, smoking status, esophageal fistula and location. Patients receiving CT plus RT were associated with improved PFS (9.5 vs 3.8 months, P<0.001) and OS (21.3 vs 12.7 months, P<0.001) compared to CT alone. Compared to CT+PTDRT+MDRT, CT+PTDRT (9.8 vs 7.9 months, P = 0.066) and CT+MDRT (9.8 vs 7.1 months, P = 0.026) were associated with inferior PFS. On multivariable analysis, CT+PTDRT+MDRT, no smoking history and no fistula were associated with improved PFS. Additionally, there was no significance difference on OS between patients receiving CT+PTDRT+MDRT, CT+PTDRT and CT+MDRT (21.3 vs 20.3 vs 20.1 months, P = 0.29). CT plus RT improved PFS and OS in ESCC patients with oligometastases, and CT+PTDRT+MDRT resulted in the most favorable PFS suggesting the important role of aggressive local treatment.

1458P Real-world treatment patterns of unresectable advanced or synchronous metastatic esophageal squamous cell cancer in a Western population

1458P Real-world treatment patterns of unresectable advanced or synchronous metastatic esophageal squamous cell cancer in a Western population

PCN9 TREATMENT PATTERNS AND SURVIVAL IN UNRESECTABLE ADVANCED ESOPHAGEAL SQUAMOUS CELL CANCER IN THE SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS (SEER) MEDICARE LINKED DATA

Esophageal squamous cell cancer (ESCC) is a leading cause of cancer death worldwide. Treatment options are limited for patients who cannot undergo surgery. The study objective was to understand patterns of care, overall survival, and duration of treatment (DoT) in Medicare patients with unresectable ESCC in the United States. This was a retrospective cohort study using SEER data linked with Medicare claims. Patients aged ≥66 years with a primary, pathologically confirmed diagnosis of unresectable advanced or metastatic ESCC between 2010–2015 were included, and were followed through 2016. Outpatient systemic treatment was identified using Medicare claims. First-line, second-line, and third-line therapies were inferred based on changes and gaps in treatment. Patients were followed until death, end of follow-up, second primary cancer, or switch to managed care. The Kaplan-Meier estimator was used to estimate unadjusted median survival and DoT. This study identified 756 ESCC patients. Mean age was 75 years, 64% were male, 71% white, 52% had TNM Stage T4b or M1, and 79% had no mobility limitation indicators at diagnosis. Mean follow-up time from diagnosis was 15.6 months and 75% of patients died during follow-up. Of all diagnosed patients, 459 (61%) received first-line treatment, 104 (14%) received second-line, and 26 (3.4%) received third-line. Median survival was 11.5 months (95% CI 10.3-14.1) for first-line, 5.7 months (95% CI 5.0-8.5) for second-line, and 5.3 months (95% CI 2.5-19.0) for third-line patients. DoT (first to last dose) by line was 1.4, 1.6, and 1.4 months. Paclitaxel plus carboplatin (n=206, 45%) was the most common first-line regimen; docetaxel or paclitaxel monotherapy (n=21, 20%) was the most common second-line regimen. Patients with ESCC have poor overall survival, and few receive second- or third-line treatment. These results highlight the need for more effective treatment options in second-line and later lines of treatment.

Prognostic significance of sarcopenia in metastatic esophageal squamous cell carcinoma.

4068 Background: Sarcopenia is defined as low skeletal muscle mass and represents a quantifiable marker of frailty. Disease related symptoms of anorexia, nausea and dysphagia, in addition to reduced physical activity contribute to muscle wasting in metastatic esophageal squamous cell cancer (MESCC) patients. This study set out to evaluate the prognostic utility of sarcopenia and its association with nutritional indices. Methods: MESCC patients (pts) with available abdominal CT imaging, attending Princess Margaret Cancer Centre between 2011 and 2016, were identified from the institutional database. Skeletal muscle index (SMI), normalized by height, was calculated at the third lumbar (L3) vertebra using SliceOMatic software. SMI cutoffs for sarcopenia were 34.4cm2/m2 in females and 45.4cm2/m2 in males based on previously established consensus. Nutritional risk index (NRI) was calculated using weight and albumin with malnutrition defined as &lt; 97.5. Results: Of the 58 pts analyzed, 26 presented with de novo MESCC, median age was 64 (range 48-85), 30 pts were ECOG PS ≤1 and 45% received systemic therapy. 93% of pts experienced weight loss &gt; 5% in the 3 months preceding diagnosis and median BMI was 20.4 (range 16.3-34.9). Twenty-four (41%) pts were sarcopenic (SP) with differences in BMI and NRI (p &lt; 0.05) compared to non-sarcopenic (NSP) pts. Median BMI in SP pts was 18.9 (16.3-25.6), 46% had a BMI &lt; 18.5 and none were obese (BMI ≥ 30). By NRI, 58% of SP pts were malnourished. Males comprised 71% of SP pts (p = 0.03) but no difference from NSP MESCC pts was identified with age, race, ECOG PS or smoking status with univariate analysis. Median overall survival (OS) was 6 months; 4.2 in SP pts and 6.2 in NSP pts. Significant difference was identified with NRI (p = .0.009) but not sarcopenia (p = 0.247) or BMI (p = 0.393). With a multi-variate Cox model for NRI and sarcopenia, including age, sex, race, and ECOG PS, only ECOG PS was a significant predictor of mortality, HR for 2-3 vs 0-1 of 5.4 (2.5-11.9) p &lt; 0.001. Conclusions: Sarcopenia at diagnosis was not associated with OS. NRI was superior to BMI alone with respect to discriminating pt outcomes, however ECOG PS was the only measure significantly associated with survival.

Cisplatin and 5-Fluorouracil with or Without Epidermal Growth Factor Receptor Inhibition Panitumumab for Patients with Non-Resectable, Advanced or Metastatic Esophageal Squamous Cell Cancer: A Prospective, Open-Label, Randomised Phase 3 AIO/EORTC Trial (Power)

Background: Advanced unresectable esophageal squamous cell cancer (ESCC) is treated with palliative chemotherapy of cisplatin and 5-fluorouracil (CF). Targeting epidermal growth factor receptor (EGFR) with antibodies panitumumab (P) or cetuximab with chemotherapy enhanced overall survival (OS) in metastatic colorectal cancer or squamous cell cancer of head and neck. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in confirmed advanced ESCC. Methods: 146 patients, not curatively resectable and not qualified for definitive radio-chemotherapy were randomised 1:1 to CF (cisplatin [100 mg/m² i.v., day 1] and 5-fluorouracil [1000 mg/m²/day i.v., days 1-4]), versus CF plus P [9 mg/kg, i.v., day 1], each q3-week cycle) until progressive disease or inacceptable toxicity. Safety was reviewed by a pre-planned Monitoring Board after 40, 70 and 100 patients completing at least one cycle. After 53 patients enrolled, cisplatin was amended from 100 to 80 mg/m². Findings: The academic phase 3 trial was terminated early for futility on an interim efficacy analysis: median OS favoured CF over CFP, regardless of cisplatin dose (HR 1·77, 95%CI 1·06-2·98; p=0·028). In the final analysis, median OS was 10·2 vs 9·4 months for CF vs CFP, respectively (HR 1·17, 95%CI 0·79-1·75; p=0·43). Most deaths were related to disease progression, 44 (56·4%) in CF and 34 (43·6%) in CFP. Objective responses (27/73 [37·0%]) were identical in both arms. Most common severe adverse events were kidney injury (3 [4·3%] vs 7 [9·7%]), general deterioration (5 [7·1%] vs 5 [6·9%]), and dysphagia (4 [5·7%] vs 4 [5·6%]) in CF vs CFP, respectively. High levels of soluble (s)EGFR were associated with worse PFS. sEGFR was induced under CFP. Interpretation: Cisplatin/5-fluorouracil is an established palliative regimen in unselected advanced or metastatic ESCC patients. EGFR inhibition added to CF did not improve survival. Biomarker results support further liquid biomarker studies. Trial Registration Number: The study is registered with ClinicalTrials.gov (NCT01627379) and EudraCT (2010-020606-15). Funding: The trial was funded by AIO-Studien-gGmbH. Partial financial support and panitumumab were provided by Amgen Inc. Declaration of Interest: MM has travel support and advisory role for Amgen. FL reports personal fees from Amgen. All other authors declare that they have no conflicts of interest during the conduct of the study. Ethical Approval: The clinical study protocol was reviewed and approved by the responsible ethics committees of all participating sites. The trial was conducted in accordance with the principles of the International Conference on Harmonisation on Good Clinical Practice. All patients gave written informed consent before enrolment and any trial-specific procedures.

Phase II Study of S-1 plus Cisplatin as First-Line Therapy in Patients with Metastatic Esophageal Carcinoma

Background: Patients with metastatic esophageal squamous cell cancer (ESCC) need safer and more efficacious treatments. The aim of this phase II study was to investigate the efficacy and safety of S-1 plus cisplatin as first-line therapy in metastatic ESCC. Patients and Methods: 50 patients with metastatic ESCC who had not received prior systemic chemotherapy for metastatic disease were enrolled. Patients received S-1 at 40 mg/m² divided into 2 daily doses for 14 days and cisplatin at 75 mg/m² on day 1 or 25 mg/m² on days 1-3 intravenously, repeated every 21 days with a maximum of 6 cycles. Results: 47 patients were assessable for response and 18 patients achieved a partial response, giving an overall response rate of 38.3%. Among those who had objective responses, a large percentage (72.2%) quickly showed remarkable tumor shrinkage during the first 2 cycles. 18 (38.3%) patients had stable disease. The median progression-free survival was 5.6 months, and the median overall survival was 12.0 months. Toxicity was mild to moderate and generally tolerable. Conclusion: The combination of S-1 plus cisplatin was a well-tolerated and convenient chemotherapy regimen with promising efficacy.

Prognostic significance of malnutrition in metastatic esophageal squamous cell carcinoma.

171 Background: Disease related symptoms including anorexia, nausea and dysphagia lead patients with esophageal cancer to become malnourished. Malnourishment can result in systemic inflammation, reduced treatment tolerance, poorer quality of life and decreased overall survival. Currently weight loss is the main clinical measure of malnutrition, and thus we set out to evaluate the prognostic utility of alternative screening tools of malnutrition. Methods: Patients with metastatic esophageal squamous cell cancer (MESCC) attending the Princess Margaret Cancer Centre, between January 2011 and December 2016, were identified from the institutional gastroesophageal database. Nutritional Risk Score (NRS), Nutritional Risk Index (NRI) and Neutrophil Lymphocyte Ratio (NLR) were calculated and correlated with clinical-pathological variables and survival. Malnutrition was defined as NRS ≥ 3, NRI &lt; 97.5 and NLR ≥ 3. Results: Of the 64 consecutive patients, 30 (47%) presented with de novo metastatic disease and 34 (53%) with recurrence. The median age was 62 years (range 40-85), 47 patients were ECOG PS ≤ 2 and 29 (45%) received systemic chemotherapy. 90% of patients experienced weight loss &gt; 5% prior to diagnosis and median BMI was 20.1 (range 14.3-34.9). NRI identified 37 (58%) and NRS 45 (70%) patients as malnourished. Both were associated with poorer ECOG PS (p = 0.012 and p = 0.027 respectively). No difference was identified with sex, smoking status or albumin with univariate analysis. NRI did not associate significantly with age. Median overall survival was 5months; 8.1-9 months with normal nutrition and 2.8-3.2 months in malnourished patients. Kaplan Meier analysis revealed significant difference in overall survival (malnutrition vs. normal nutrition) using NRS (p = 0.029) and NRI (p = 0.001) but not weight (p = 0.509) or NLR (p = 0.69). Conclusions: Patients with MESCC identified as malnourished at the time of diagnosis have inferior survival outcomes. Malnutrition tools are superior to weight alone with respect to discriminating outcomes in this patient population. Further investigation is needed in larger patient cohorts; to identify those at risk, initiate early supportive interventions and improve patient outcomes.

O-010 - Cisplatin/5-fluorouracil +/- panitumumab for patients with non-resectable, advanced or metastatic esophageal squamous cell cancer: A randomized phase III AIO/EORTC trial with an extensive biomarker program

O-010 - Cisplatin/5-fluorouracil +/- panitumumab for patients with non-resectable, advanced or metastatic esophageal squamous cell cancer: A randomized phase III AIO/EORTC trial with an extensive biomarker program

Nutritional parameters for nutritional intervention as predictive factors in patients with metastatic esophageal squamous cell cancer.

e22185Background: Proper nutritional support affects the treatment outcome in cancer. However, the role of nutritional intervention (NI) in patients (pts) with metastatic esophageal squamous cell c...

Prognostic significance of nutritional risk index in patients with metastatic esophageal squamous cell cancer.

156 Background: It has been suggested that nutritional indicators predict the prognosis of esophageal cancer. Nutritional risk (NR) as prognostic factor evaluated by NR index (NRI) in metastatic esophageal squamous cell cancer (ESCC) has not been clarified. Methods: We retrospectively reviewed the data of consecutive patients (pts) with metastatic ESCC who received chemotherapy (CTx) as initial treatment at Shizuoka Cancer Center between April 2008 and December 2015. The selection criteria were as follows: histologically confirmed squamous cell carcinoma; no indication for curative resection or definitive chemoradiotherapy (dCRT); adequate organ function; no prior CTx, radiotherapy (RT) or chemoradiotherapy; no other advanced malignancies. NR was calculated by following formula: NRI = (1.489*serum albumin) + (41.7*present body weight [BW] / ideal BW). NR was classified into 4 groups according to NRI: major (NRI &lt; 83.5), moderate (NRI = 83.5-97.5), mild (NRI = 97.5-100), none (NRI &gt; 100). Multivariate analysis was carried out using cox proportional hazard to estimate the hazard ratio for overall survival (OS). Results: The patients’ characteristics of 138 pts who met the selection criteria were as follows: median age (range), 67 (33-86) years; male/female, 123/15; performance status (PS) 0/1/2, 62/68/8; number of metastatic sites 1/2/3/4, 55/56/23/4; smoking history -/+, 19/119; previous esophagectomy -/+, 118/20; median skeletal muscle index (range), 44.5 (27.8-63.2); median body mass index (range), 20.3 (14.3-27.4); NR major/moderate/mild/none 22/37/26/53; median serum C-reactive protein (CRP) level (range), 0.75 (0.01-20.48) mg/dL. The most common chemotherapy regimen used was fluoropyrimidine plus cisplatin (93%), and 70 patients (50%) received concomitant RT. Median OS was 4.6 months in pts with major NR and 11.8 months in others (p &lt; 0.001). Multivariate analysis for OS identified PS 2, female sex, metastatic sites &gt; 2, CRP ≥ 1mg/dL, and major NR independently associated with poor survival. Conclusions: Major NR calculated by NRI formula associated with poor survival in pts with metastatic ESCC.

CheckMate 648: A randomized phase 3 study of nivolumab plus ipilimumab or nivolumab combined with fluorouracil plus cisplatin versus fluorouracil plus cisplatin in patients with unresectable advanced, recurrent, or metastatic previously untreated esophageal squamous cell carcinoma.

TPS193 Background: Esophageal cancer (EC) is the sixth most common cause of cancer-related death worldwide, with a 5-y survival rate of 5%–8% in pts with metastatic disease. First–line platinum-based doublet chemotherapy (CTX) provides a modest survival benefit in pts with metastatic squamous cell EC (mESCC), with a median OS of 7.6 months. Over 40% of pts with EC have PD-L1+ tumors, which are associated with worse OS outcomes. Nivolumab (NIVO), an anti–PD-1 mAb, demonstrated efficacy and a manageable safety profile in pts with ESCC. In the phase 2 ATTRACTION-1 trial, NIVO 3 mg/kg produced an ORR of 17% and median OS of 10.8 months in heavily pretreated pts with ESCC (Kudo T et al Lancet Oncol 2017). NIVO + ipilimumab (IPI) yielded enhanced responses with a manageable safety profile in multiple tumor types. Similarly, NIVO + platinum-based CTX resulted in encouraging clinical activity and an acceptable safety profile in pts with metastatic gastric cancer and SCC NSCLC. This randomized phase 3 study will evaluate the efficacy and safety of NIVO + IPI or NIVO + fluorouracil (5-FU)/cisplatin (Cis) vs 5-FU/Cis as first-line treatment (Tx) in pts with advanced (adv) or mESCC (CheckMate 648; NCT03143153). Methods: 939 pts aged ≥ 18 y with histologically confirmed unresectable advanced, recurrent or mESCC, not amenable to curative approaches, and no prior systemic therapy for advanced/metastatic disease, with adequate organ function and ECOG PS 0 or 1 will be randomized 1:1:1 to NIVO + IPI, NIVO + 5-FU/Cis or 5-FU/Cis. Pts with autoimmune diseases, serious or uncontrolled medical disorders; active infections or positive for HIV, AIDS, or hepatitis B/C, indicating acute or chronic infection and/or detectable virus; and previous Tx with other therapy targeting T-cell co-stimulation or immune checkpoint pathways are excluded. Primary endpoints are OS and PFS by central assessment in pts with a PD-L1+ tumor (defined as PD-L1 expression on ≥ 1% of tumor cells). Secondary endpoints include ORR, PFS, and OS in all pts, as well as ORR in pts with PD-L1+ tumors. Clinical trial information: NCT03143153.

Cisplatin/5-FU (CF) +/- panitumumab (P) for patients (pts) with non-resectable, advanced, or metastatic esophageal squamous cell cancer (ESCC): An open-label, randomized AIO/TTD/BDGO/EORTC phase III trial (POWER).

4011 Background: Most ESCC pts have advanced disease at time of diagnosis. Chemotherapy (CTX) is used to improve quality of life (QoL) and overall survival (OS), but still with limited impact. Prior studies suggested increased efficacy of EGFR antibodies (AB) combined with CF (Lorenzen, Ann Oncol 2009). Methods: This open-label, randomized (1:1), multicenter, multinational phase III included pts with non-resectable, advanced or metastatic ESCC (RECIST1.1), not radiochemotherapy (RCTX) eligible and ECOG 0-1. Previous CTX in metastatic setting, concurrent RCTX and exposure to EGFR-AB were excluded. Pts received CF (C 100 mg/m² d1 + F 1000 mg/m²/d, d1-4) or CFP (9 mg/kg d1) q3 weeks until disease progression. Due to more Gr3-4 SAEs in the first 60 Pts with CFP, C was reduced to 80mg/m²d1 Tumor assessment was performed q9 weeks. Primary objective was OS: superiority of CFP (9 months [mo]) over CF (6 mo) with 300 pts (90% power). Results: Between 6.2012-5.2015, 146/155 pts were randomized. After interim analysis for futility, the trial was stopped. 60(83%) of CFP and 55(79%) of CF pts had any AE, mostly diarrhea, hypokalemia, hypomagnesaemia, rash, and hand-foot syndrome. Main Gr≥3 AEs were low neutrophils 21/ 24% and anemia 13/16 % for CFP vs CF, respectively. Gr 3-4 skin reactions and rash were higher in CFP (10%) vs CF (0%). Overall, 51/72 (71%) of CFP and 36/70 (51%) of CF had SAE. Main SAE were dysphagia, acute kidney injury, diarrhea, fevers and febrile neutropenia in 6/6%, 7/4%, 7/3%, 3/6% and 6/1% for CFP vs CF, respectively. For all CFP vs CF pts, median OS was 9.4 vs. 10.2 mo (hazard ratio (HR) 1.17, 95%CI 0.79-1.75; P=0.43). For 56 pts treated with cisplatin 100mg/m²d1, OS was 9.4 vs. 12.9 mo (HR 1.83, 95 % CI 0.98-3.42; P=0.06). After C was reduced (80mg/m²), OS (85 pts) favored CFP vs CF, with 9.8 vs. 8.3 mo (HR 0.84, 95%CI 0.49-1.43; P=0.51). Median PFS for all CFP vs CF pts, was 5.3 vs. 5.8 mo. (HR 1.21, 95%CI 0.85-1.73; P=0.29) respectively. Conclusions: Addition of Panitumumab to CF provided no additional benefit to chemotherapy alone as first-line treatment of ESCC. Biomarker program is going on for further analyses. Clinical trial information: NCT1627379.

LBA-04The E-DIS study, a randomized discontinuation trial of first-line chemotherapy (CT) in patients with metastatic squamous-cell esophageal cancer (MSEC): efficacy and quality of life results

LBA-04The E-DIS study, a randomized discontinuation trial of first-line chemotherapy (CT) in patients with metastatic squamous-cell esophageal cancer (MSEC): efficacy and quality of life results