474 Multiple combinational strategies of immunotherapy for esophageal squamous cell carcinoma: one institutional experience in Taiwan since 2016

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A505-A505
Author(s):  
Jo-Pai Chen ◽  
Wei-Chen Lu ◽  
Ruey-Long Hong
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clinical Benefit ◽  
Response Rate ◽  
University Hospital ◽  
List Type ◽  
Duration Of Response ◽  
Institutional Experience

BackgroundEsophageal squamous cell carcinoma is still a health burden in Taiwan. In R/M setting, the prognosis becomes worse. ESCC is still an immunogenic cancer. In randomized 2nd line ATTRACTION-3 study(nivolumab vs taxane after PF failure), median OS improved from 8.4 months in chemotherapy to 10.9 months in nivolumab(HR, 0.77; 95% CI, 0.62–0.96; p =0.019). The median duration of response was 3.9 months and 6.9 months. Nivolumab is a new 2nd line option for ESCC.MethodsFrom early 2016 to early 2020, 15 advanced ESCC patients had ever received immunotherapy-containing regimens in Yun-lin Branch of National Taiwan University Hospital and were analyzed.ResultsThe overall response to immunotherapy-containing regimens was 60%(9/15) and clinical benefit was 80%(12/15). 2nd line nivolumab was given in 3 cases; response rate was33% and clinical benefit was 67%. 2nd line afatinib combined with anti-PD1 was given in 9 case; response rate was 67% and clinical benefit was 78%. The response rate of 2nd line afatinib & pembrolizumab was 75%(3/4); however, Gr. III pneumonitis & Gr. II hepatitis were noted in the patient with progression. The response rate of 2nd line afatinib & nivolumab was 60%(3/5) and clinical benefit was 80%(4/5); skin rash and diarrhea were often found. 1st line afatinib combined with anti-PD1 was given in 3 patients; response rate was 67% and clinical benefit was 100%. The response rate of 1st line afatinib & nivolumab was 100%(2/2).ConclusionsEGFR TKIs have multiple immuno-modulatory effects and may increase immunotherapy benefits in ESCC. Anti-PD1 and anti-CTLA4, another possible rationale, could bring more benefits maybe in 1st line CheckMate649 study.AcknowledgementsNilTrial RegistrationN/AEthics ApprovalN/AConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferencesNil

scholarly journals Concurrent chemoradiotherapy with S-1 compared with concurrent chemoradiotherapy with docetaxel and cisplatin for locally advanced esophageal squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Grade 3

Abstract Background This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. Results A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). Conclusion CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

scholarly journals Concurrent Chemoradiotherapy with S-1 Compared with Concurrent Chemoradiotherapy with Docetaxel and Cisplatin for Locally Advanced Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Significant Difference

Abstract Background: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients who had locally advanced ESCC and received CCRT with S-1 (70mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25mg/m2) and cisplatin (25mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Treatment-related toxicities, response rate, and survival outcomes were compared between groups. Results: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than in the DP group (22.2% versus 45.6%, p = 0.002). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% versus 25.0%, p = 0.275). Conclusion: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

scholarly journals TP63, SOX2 and KLF5 Establish Core Regulatory Circuitry and Construct Cancer Specific Epigenome in Esophageal Squamous Cell Carcinoma

2019 ◽  
Author(s):  
Yan-Yi Jiang ◽  
Yuan Jiang ◽  
Chun-Quan Li ◽  
Ying Zhang ◽  
Pushkar Dakle ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
List Type ◽  
Circular Chromosome ◽  
Super Enhancer

SUMMARYTranscriptional network is controlled by master transcription factors (TFs) and cis-regulatory elements through interacting with target sequences and recruiting epigenetic regulators. By integration of enhancer profiling and chromatin accessibility, we establish super-enhancer (SE) mediated core regulatory circuitry (CRC) for esophageal squamous cell carcinoma (ESCC) and identify tumor cells-dependent CRC TFs-TP63, SOX2 and KLF5. They preferentially co-occupy SE loci and form a positive interconnected auto-regulatory loop through SEs to orchestrate chromatin and transcriptional programming. SE-associated oncogene-ALDH3A1 is identified as a novel CRC target contributing to ESCC viability. Using circular chromosome conformation capture sequencing (4C-seq) and CRISPR/Cas9 genome editing, the direct interaction between TP63 promoter and functional enhancers which is mediated by CRC TFs is identified. Deletion of each enhancer decreases expression of CRC TFs and impairs cell viability, phenocopying the knockdown of each CRC TF. Targeting epigenetic regulation by inhibition of either the BET bromodomain or HDAC disrupts the CRC program and its dependent global epigenetic modification, consequently suppressing ESCC tumor growth. Importantly, combination of both compounds result in synergistic anti-tumor effect.Graphical AbstractHIGHLIGHTSSuper-enhancers mediated transcriptional regulatory circuitry is established for ESCCTP63, SOX2 and KLF5 as CRC TFs co-localize super-enhancer loci to orchestrate chromatin accessibility and transcriptional dysregulationComplex interaction between functional enhancers and TP63 promoter is mediated by CRC TFsALDH3A1 is a key downstream target of ESCC CRC and is essential for ESCC cell survivalBET degrader-ARV-771 and HDAC inhibitor-Romidepsin synergistically inhibit ESCC tumor growth

Camrelizumab plus apatinib successfully treated a patient with advanced esophageal squamous cell carcinoma

Immunotherapy ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1161-1166 ◽  
Author(s):  
Zheng Yan ◽  
Zhi-Hua Yao ◽  
Shu-Na Yao ◽  
Hai-Ying Wang ◽  
Jun-Feng Chu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Poor Response ◽  
Complete Response ◽  
Combination Regimen ◽  
Pet Ct ◽  
Duration Of Response ◽  
Mild Toxicity

Aim: Advanced esophageal squamous cell carcinoma (ESCC) is a lethal disease with poor response to conventional chemotherapy. Immunotherapy showed better activity than chemotherapy in late-line treatment. However, the rate and duration of response are far from satisfactory. The efficacy of an anti-angiogenic agent combined with immunotherapy for ESCC is unknown. Results: A patient with ESCC experienced disease relapse after chemo-radiotherapy. The disease progressed after combined chemotherapy. A combination regimen of the PD-1 inhibitor camrelizumab and the anti-angiogenic agent apatinib was administered. The patient achieved a PET/CT-confirmed durable complete response with mild toxicity. Conclusion: The PD-1 inhibitor combined with the anti-angiogenic agent is effective and safe for the treatment of ESCC. This regimen is worth investigation in clinical trials.

Phase II trial of irinotecan and cisplatin combination as first-line chemotherapy in patients with advanced esophageal squamous-cell carcinoma: An interim report.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 137-137
Author(s):  
X. Zhang ◽  
L. Shen ◽  
J. Li ◽  
Y. Li ◽  
J. Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Response Rate ◽  
Objective Response ◽  
Complete Response ◽  
Carcinoma Of The Esophagus ◽  
Metastatic Squamous Cell Carcinoma ◽  
Grade 3

137 Background: Although the irinotecan and cisplatin combination has been used in esophageal cancer treatment, we tested the combination specifically in unresectable or metastatic esophageal squamous cell carcinoma with different doses to decrease the toxicity and keep the efficacy. Methods: Patients were eligible if they had histologic proof of unresectable or metastatic squamous cell carcinoma of the esophagus, between 18-75 years of age with a Karnofsky performance status ≥ 80. No prior chemotherapy was allowed. Patients were treated with irinotecan 130 mg/m2 and cisplatin 60 mg/m2 repeated 3 weeks. Response was evaluated every two cycles of treatment by using RECIST criteria. The sample size was calculated using Simon's 2-stage design. The primary end point of the study was objective response rate. The second end points are PFS and toxicity. Accrual was planned to a total of 46 patients with the targeted response rate of 50%. The first stage requires at least 7 or more out of 16 patients to have a confirmed partial or complete response before proceeding to the second stage. Results: Twenty one patients have been enrolled so far, of which 16 patients were assessable for response. The overall response rate was 43.8%(7/16), including one complete response (6.3%) and six partial response (37.5%). Among 13 patients who presented with dysphagia at baseline, 10 (62.5%) had the symptom either completely resolved or significantly improved. The most common toxicities were neutropenia, diarrhea and alopecia. Seven patients (33.3%) developed grade 3 neutropenia and one had (4.8%) with febrile neutropenia. One patient (4.8%) had grade 3 diarrhea. There were no treatment-related deaths. Conclusions: The combination of irinotecan plus cisplatin with lower doses showed equivalent efficacy and less toxicity in patients with unresectable or metastatic squamous-cell carcinoma of the esophagus. The study is ongoing. No significant financial relationships to disclose.

TROPiCS–03: A phase II open-label study of sacituzumab govitecan (SG) in patients with metastatic solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS3648-TPS3648
Author(s):  
Ashish Saxena ◽  
Loren S. Michel ◽  
Quan Hong ◽  
Karrie Hilsinger ◽  
Charu Kanwal ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Endometrial Cancer ◽  
Cell Carcinoma ◽  
Solid Tumors ◽  
Squamous Cell ◽  
Clinical Benefit ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Open Label

TPS3648 Background: Trophoblast cell surface antigen (Trop-2) is highly expressed in many epithelial cancers (non–small-cell lung cancer [NSCLC], endometrial cancer, urothelial carcinoma [UC], and triple-negative breast cancer [TNBC]) and has been linked to aggressive disease and poor prognosis. SG is a Trop-2–directed antibody drug conjugate containing SN-38 (active metabolite of irinotecan) with a 7.5:1 drug-to-antibody ratio and unique hydrolyzable linker that allows for extracellular bystander effect. The phase 1/2 IMMU-132-01 basket study reported clinical activity with SG in patients with multiple tumor types not selected for Trop-2 expression including NSCLC (objective response rate [ORR]: 17%), TNBC (ORR: 33%), and UC (ORR: 31%).1-3 Results from the overall safety population (N=420) from this study found that SG was tolerable, with a predictable and manageable safety profile, and low discontinuation rates due to AEs. Methods: To test a biomarker-enrichment strategy with Trop-2, the TROPiCS-03 (TROP-2 Investigations in Cancer with SG) study was initiated. TROPiCS-03 (NCT03964727) is a multi-cohort, open-label, phase 2 study in patients with metastatic solid tumors - presently NSCLC (adenocarcinoma and squamous cell carcinoma), head and neck squamous cell carcinoma, and endometrial cancer - selected based on elevated Trop-2 expression by a validated IHC assay. Patients receive SG (10 mg/kg IV, days 1 and 8 every 21 days) and continue treatment until lack of clinical benefit or unacceptable toxicity. The primary endpoint is objective response rate (local assessment) and additional endpoints include clinical benefit rate, duration of response, progression-free survival, and safety. Females or males ≥18 years old who are histologically documented to have locally advanced or metastatic (M1, stage 4) solid tumors of the above types are eligible. Patients must have ECOG 0 or 1 and adequate clinical laboratory results to be enrolled. All subjects will have progressed after prior platinum-based chemotherapy and programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1) directed therapy. Patients who have previously received topoisomerase I inhibitors and those with known active CNS metastases are excluded. Approximately 160 patients will be enrolled in the trial overall; enrollment in the NSCLC cohort is currently in progress. References: Heist RS et al. J Clin Oncol. 2017;35:2790-7, Bardia A et al., NEJM. 2019;380:741-51.,Tagawa ST et al., Oral presentation; ASCO-GU 2019, San Francisco, CA. Clinical trial information: NCT03964727 .

Sign in / Sign up

Export Citation Format

Share Document