Nivolumab in advanced esophageal squamous cell carcinoma (ATTRACTION-1/ONO-4538-07): Minimum of five-year follow-up.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 207-207
Author(s):  
Ken Kato ◽  
Yuichiro Doki ◽  
Takashi Ura ◽  
Yasuo Hamamoto ◽  
Takashi Kojima ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Squamous Cell ◽  
Group Performance ◽  
Objective Response

207 Background:ATTRACTION-1/ONO-4538-07 (AT-1), an open-label, single-arm, multicenter phase 2 clinical trial conducted in Japan, evaluated the clinical activity and safety of nivolumab in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory/intolerant to fluoropyrimidine-, platinum-, and taxane-based chemotherapy. We previously reported the 2-year follow-up findings of AT-1, in which nivolumab demonstrated antitumor activity with a manageable safety profile for these patients. Here we report the final findings from AT-1 at a minimum follow-up of 5 years. Methods:Patients aged ≥20 years with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 received 3 mg/kg nivolumab intravenously every 2 weeks in 6-week cycles until disease progression or unacceptable toxicity. The primary endpoint was centrally-assessed objective response rate (ORR), defined as the proportion of patients whose best overall response was either a complete or partial response. Secondary endpoints included overall survival (OS), investigator-assessed ORR, progression-free survival (PFS), change in tumor burden, time to response, time to disease progression, and duration of response. Results:Between February 25 and November 14, 2014, a total of 65 patients were enrolled. Sixty-four patients were evaluated for the efficacy, and all patients were evaluated for the safety. At the final database lock on August 6, 2020, 11 (17.2%, 95% confidence interval [CI] 9.9-28.2) of 64 patients had an objective response by central assessment. The median OS was 10.8 months (95% CI, 7.4-13.9), and the estimated 5-year OS rate was 6.3% (95% CI, 2.0-14.0). The median PFS was 1.5 months (95% CI, 1.4-2.8), and the estimated 5-year PFS rate was 6.8% (95% CI, 2.2-15.1). Treatment-related adverse events that occurred with a frequency of > 10% were diarrhea and rash. The presentation will include characteristics of long-term survivors as well as detailed efficacy and safety data of nivolumab. Conclusions:This final assessment represents the longest follow-up of patients with advanced ESCC treated with nivolumab. Nivolumab demonstrated continued long-term efficacy in these patients based on a minimum of 5-year long-term survival update of AT-1. Furthermore, no new safety signals with nivolumab were identified during long-term follow-up. These findings are consistent with those of nivolumab monotherapy for various types of cancer. Clinical trial information: No.142422.

Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR-1210), a novel anti-PD-1 antibody.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15559-e15559
Author(s):  
Xi Wang ◽  
Bo Zhang ◽  
Xuelian Chen ◽  
Hongnan Mo ◽  
Dawei Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Lactate Dehydrogenase ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Squamous Cell ◽  
Peripheral Blood ◽  
Group Performance ◽  
Blood Biomarkers

e15559 Background: A small proportion of patients with advanced esophageal squamous cell carcinoma (ESCC) could benefit from immune checkpoint inhibitors, and reliable peripheral blood biomarkers for outcomes of anti-PD-1 immunotherapy were not identified in ESCC. Methods: A total of 43 patients were retrospectively reviewed in the ESCC cohort of a phase I trial from our center. All patients received intravenous camrelizumab (SHR-1210), a novel anti-PD-1 antibody, at a dose of 60 mg, 200 mg or 400 mg (4-week interval after first dose followed by a 2-week schedule) and repeated every two weeks until disease progression or intolerable toxicity. The associations between lactate dehydrogenase (LDH) as well as other peripheral blood biomarkers at baseline and the efficacy of camrelizumab were also investigated. Results: With a median follow-up of 19.6 months, the overall response rate was 25.6% (11/43), including one complete response. Median progression-free survival (PFS) and overall survival were 2.0 months (95% CI: 0-4.1 months) and 8.0 months (95% CI: 7.2-8.8 months), respectively. Notably, four patients achieved a PFS exceeding 12 months, including three patients with a long-lasting duration of response over 1 year. Patients with an elevated baseline lactate dehydrogenase had lower tumor response rates (8.3% vs. 32.3%, p = 0.02) as well as shorter PFS (median: 1.8 vs. 4.0 months; HR 0.39, p = 0.002) and overall survival (median: 4.2 vs. 10.4 months; HR 0.22, p < 0.0001) compared with patients with normal levels. An increase of lactate dehydrogenase level during treatment was significantly associated with disease progression (p = 0.014). Multivariate Cox analysis identified LDH (HR = 0.18), C-reactive protein (HR = 0.27), number of involved organs (HR = 0.31), absolute monocyte count (HR = 0.33) and Eastern Cooperative Oncology Group performance status (HR = 0.36) as independent prognostic factors. Conclusions: Serum LDH, as is readily available in routine clinical practice, is a potential marker for response and a powerful independent factor for survival in advanced ESCC patients receiving anti-PD-1 treatment.

Neoadjuvant PD-1 blockade in combination with chemotherapy for patients with resectable esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 220-220
Author(s):  
Chao Cheng ◽  
Weixiong Yang ◽  
Wenfang Chen ◽  
Sai-Ching Jim Yeung ◽  
Xiangbin Xing ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Regression ◽  
Objective Response ◽  
Neoadjuvant Treatment ◽  
R0 Resection

220 Background: Programmed death-1 (PD-1) blockade may induce tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC), but little is known about the efficacy of PD-1 blockade in neoadjuvant therapy of resectable ESCC. Methods: Under an approved clinical trial protocol, a pilot study was conducted by enrolling patients with untreated, resectable (stage II or IIIA) ESCC. After written informed consent, each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab (200mg), albumin-paclitaxel (260mg/m2) and carboplatin (area under the curve = 5) followed by surgical resection about 6 weeks after the first dose. The primary end points were safety and feasibility. We also reported the objective response rate (ORR), disease control rate (DCR) and tumor pathological response. Results: Between January 19, 2020, and July 21, 2020, we assessed 35 patients for screening, of whom 20 patients were enrolled. Neoadjuvant combination of camrelizumab, carboplatin and albumin-paclitaxel had an acceptable side-effect profile, and was not associated with delays in surgery. The ORR was 85%, and the DCR was 100%. Eighteen (90%) patients were taken into the surgery, and all of them successfully underwent R0 resection. Five (5/18 = 27.8%) patients had a pathological complete response (pCR), and eight (44.4%) patients had major pathological responses (MPR).The most common treatment-related grade 1–2 adverse events were leukopenia (12, 60%), neutropenia (11, 55%) and nausea (8, 40%). Two (10%) patients suffered grade 3 neutropenia. There was no grade 4 adverse events and treatment-related deaths. Conclusions: Neoadjuvant camrelizumab plus carboplatin and albumin-paclitaxel had manageable treatment-related toxic effects, did not delay surgery. This regimen induced pCR or MPR in 72.2% of resected tumor, demonstrating its antitumor efficacy in resectable ESCC. Clinical trial information: ChiCTR2000028900.

Long-term Follow-up after Complete Ablation of Early Esophageal Squamous Cell Carcinoma with Argon Plasma Coagulation

2014 ◽  
Vol 65 (4) ◽  
pp. 314-321
Author(s):  
Kenro Kawada ◽  
Tatsuyuki Kawano ◽  
Yasuaki Nakajima ◽  
Toshihiro Matsui ◽  
Masafumi Okuda ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Argon Plasma Coagulation ◽  
Argon Plasma ◽  
Plasma Coagulation ◽  
Long Term Follow Up

Long-term results of salvage endoscopic treatment for patients with local failure after chemoradiotherapy for esophageal squamous cell carcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 207-207
Author(s):  
Ken Hatogai ◽  
Tomonori Yano ◽  
Takashi Kojima ◽  
Masakatsu Onozawa ◽  
Toshihiko Doi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Local Failure ◽  
Long Term Results ◽  
Long Term Outcome

207 Background: Local failure is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC), and salvage surgery presents high morbidity and mortality rates. We have introduced photodynamic therapy (PDT) and endoscopic resection (ER) for local failures to develop a less invasive salvage treatment.The aim of this retrospective study was to clarify the long-term outcome of salvage endoscopic treatments (SET). Methods: Between 1998 and 2008, 716 patients with ESCC were treated with definitive CRT in our institution. There were 314 patients with incomplete response and 103 with local recurrence after achieving complete response (CR) once. The indication criteria of SET were as follows: 1) absence of lymph node and distant metastasis and 2) local failures limited within T2. ER was performed for local failures limited to T1b (SM1), and PDT was performed for lesions invading T1b (SM2) or T2, in patients who could not tolerate or who refused surgery. We assessed overall survival (OS), relapse-free survival (RFS), and also prognostic factors. This study was approved by an institutional review board. Results: A total of 164 patients with local failure underwent SET (ER: 58, PDT: 106). The characteristics before CRT were as follows: T1/2/3/4, 44/25/75/20; N0/1, 85/79; stage I/II/III/IV, 35/59/57/13; and those of before SET were as follows: T1/2, 126/38; residue/recurrence, 76/88. ER achieved curative resection in 51 (87.9%), and PDT achieved CR in 61 (57.5%) patients. With a median follow up period of 73 months, the OS and RFS rates at 5 years from SET were 38.6% (95% CI 31.0–46.2) and 28.1% (95% CI 21.0–35.2). Multivariate analysis revealed 2 preferable prognostic factors in common for OS and RFS, N0 before CRT (OS HR: 0.47 [95% CI 0.32–0.69], RFS HR: 0.61 [95%CI 0.43–0.87]) and a period from initiation of CRT to SET longer than 6 months (OS HR: 0.57 [95%CI 0.39–0.84], RFS HR: 0.67 [0.47–0.95]). After 5 years of follow up, 58 patients (35.4%) were alive without any metastasis under esophagus preservation. Conclusions: SET demonstrated a favorable outcome in an analysis of a large number of patients with local failure after definitive CRT for ESCC.

Management decision based on lymphovascular involvement leads to favorable outcomes after endoscopic treatment of esophageal squamous cell carcinoma

Endoscopy ◽  
2017 ◽  
Vol 50 (07) ◽  
pp. 662-670 ◽  
Author(s):  
Kazuya Takahashi ◽  
Satoru Hashimoto ◽  
Ken-ichi Mizuno ◽  
Takamasa Kobayashi ◽  
Kentaro Tominaga ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Management Decision ◽  
Prophylactic Therapy ◽  
Term Outcome ◽  
Long Term Outcome

Abstract Background Esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (MM) and submucosa up to 200 µm (SM1) has a risk of metastasis. The aims of this study were to investigate the long-term outcome of endoscopic submucosal dissection (ESD) for MM/SM1 ESCC and to assess the management after ESD in our hospital. Methods This was a retrospective cohort study conducted at a single institution. Patients with MM or SM1 ESCC who were treated with ESD were included. Additional prophylactic therapy was added if lymphovascular involvement (LVI) was noted in the ESD specimens. Results A total of 102 patients were analyzed. The median length of follow-up was 71.5 months (range 9 – 144 months) and the median number of CTs was 6 (range 0 – 24). LVI was found in 21 patients (20.6 %), and 12 patients underwent additional prophylactic therapy. The 5-year overall survival, disease-specific survival, and tumor-free survival rates were 84.1 %, 97.5 %, and 82.1 %, respectively. A total of 26 patients died, but only 2 of them died from ESCC. The cumulative metastasis rate was 11.8 %, and LVI was a significant predictor of metastasis (hazard ratio 5.42, 95 % confidence interval 1.39 – 21.18; P = 0.02). There were no differences between patients with MM ESCC and those with SM1 ESCC. Conclusions The long-term outcome after ESD for MM/SM1 ESCC was favorable with additional prophylactic therapy and strict adherence to follow-up. These results indicate that our management decision based on LVI is a valid approach and that ESD can be offered as a therapeutic option to MM/SM1 ESCCs.

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