scholarly journals Neoadjuvant camrelizumab plus chemotherapy in treating locally advanced esophageal squamous cell carcinoma patients: a pilot study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peng Yang ◽  
Xiao Zhou ◽  
Xuefeng Yang ◽  
Yuefeng Wang ◽  
Tao Sun ◽  
...  

Abstract Background Camrelizumab (a PD-1 inhibitor) has been used as a potential therapy in unresectable advanced esophageal squamous cell carcinoma (ESCC) along with adjuvant treatment in locally advanced ESCC, exhibiting an acceptable efficacy and safety profile. This pilot study was designed to further investigate the clinical value and tolerance of neoadjuvant camrelizumab plus chemotherapy in locally advanced ESCC. Methods A total of 16 patients with locally advanced ESCC were recruited. Patients received 2 cycles of neoadjuvant therapy including 2 doses of camrelizumab concurrent with 2 cycles of paclitaxel plus carboplatin followed by surgery 4 weeks afterward. Then, the treatment response after neoadjuvant therapy, R0 resection rate, tumor regression grade (TRG), and pathological complete remission (pCR) rate were measured. Besides, adverse events were documented. At last, progression-free survival (PFS) and overall survival (OS) were assessed. Results Generally, objective remission rate (ORR) was 81.3% whereas disease control rate (DCR) was 100% after neoadjuvant therapy. Concerning TRG grade, 31.3, 37.5, 18.8, and 12.5% patients reached TRG0, TRG1, TRG2, and TRG3, respectively. Then, pCR rate and R0 resection rate were 31.3 and 93.8%, respectively. Besides, mean PFS and OS were 18.3 months (95%CI: (16.2–20.5) months) and 19.2 months (95%CI: (17.7–20.7) months), respectively, with a 1-year PFS of 83% and OS of 90.9%. Adverse events included white blood cell decrease (37.5%), neutrophil decrease (31.3%), reactive cutaneous capillary endothelial proliferation (37.5%), and nausea or vomiting (25.0%), which were relatively mild and manageable. Conclusion Neoadjuvant camrelizumab plus chemotherapy exhibits good efficacy and acceptable tolerance in patients with locally advanced ESCC.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  

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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16029-e16029
Author(s):  
Delin Liu ◽  
Qin Zhang ◽  
Jinghua Zhu ◽  
Ting Qian ◽  
Rong Yin ◽  
...  

e16029 Background: Compared with neoadjuvant chemotherapy alone,Neoadjuvant radiochemotherapy can significantly increase pCR rate in esophageal squamous cell carcinoma and improve patient overall survival. However, the addition of radiotherapy increases the risk of adverse reactions and surgery. Neoadjuvant radiochemotherapy is currently used in < 5% of Chinese patients.The purpose of this phase II study is to assess the efficacy and safety of toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma(clinical trial registration number: ChiCTR1900025318). Methods: Patients 18–75 years old with esophageal squamous cell carcinoma confirmed by endoscopic biopsy, assessed to be locally advanced esophageal squamous cell carcinoma (cT1–cT2, N+; cT3–cT4 a, any N), and expected to be resectable were given toripalimab (240 mg d1 + PTX 175 mg/m2 + PDD 75 mg/m2 q3w) before surgery for two treatment cycles, followed by efficacy assessment. A consultation meeting with thoracic surgeons was held to assess radical surgery for patients with resectable lesions 4–6 weeks after neoadjuvant therapy was completed. pCR and postoperative-stage statistical analysis were conducted based on postoperative pathology test results. These results were used to determine the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal cancer. Results: By December 2020, 23 subjects were enrolled. Of the subjects, five withdrew without undergoing surgery (three subjects refused surgery and switched to radical radiochemotherapy, one subject progressed to PD after two cycles of neoadjuvant therapy and switched to palliative treatment, and one subject could not undergo surgery after neoadjuvant treatment and gave up the treatment) and 18 evaluable patients underwent surgery. The R0 resection rate was 100%, and T0–Tis 33.3% (6/18) achieved pCR. Among these patients, 61.1% (11/18) achieved T0–T1 after surgery, and 72.2% (13/18) achieved N0. Moreover, stage reduction effects were significant compared with preoperative TN staging. Common side-effects include nausea, vomiting, neutropenia, thrombocytopenia, rash, asthenia, constipation, and muscle soreness. Most adverse events were grades 1–2, and grades 3/4 adverse events include one case of grade 3 neutropenia and one case of grade 3 diarrhea (suspected immune-related colitis), which improved after symptomatic treatment. Conclusions: Toripalimab combined with the TP scheme showed preliminary efficacy and controllable safety in the treatment of resectable locally advanced esophageal squamous cell carcinoma and is worthy of further exploration. Clinical trial information: ChiCTR1900025318.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16033-e16033
Author(s):  
Jianqun Ma ◽  
Jinfeng Zhang ◽  
Yingnan Yang ◽  
Dayong Zheng ◽  
Xiaoyuan Wang ◽  
...  

e16033 Background: Camrelizumab has been approved as a standard therapy in the second-line treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the efficacy and safety of camrelizumab combined with commonly used neoadjuvant chemotherapy (paclitaxel and platinum) in neoadjuvant treatment of ESCC. Methods: In this single-arm, phase Ⅱ study, patients with advanced ESCC who were expected to receive neoadjuvant therapy followed by radical surgery were recruited. The patients received 2-4 cycles of camrelizumab (200mg, iv, q3w) in combination with paclitaxel (155mg/m2, iv, q3w) and nedaplatin (80mg/m2, iv, q3w) as neoadjuvant therapy, and the therapeutic effects were determined every 2 cycles. The radical surgery was performed on patients whose tumors were evaluated as resectable. The primary endpoint was pCR, and the secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Results: From May 2020 to January 2021, 24 patients with a median age of 60.5 years (50-73) were enrolled. Among them, 21 patients were available for efficacy analysis, of which 1 achieved complete response (CR), 7 achieved partial response (PR), and 13 had stable disease (SD). The ORR was 38.1% and DCR was 100%. The tumor in 10 patients shrank significantly after neoadjuvant therapy and these patients preferred radiotherapy instead of surgery as the radical therapeutic method. 2 patients abandoned surgery because of personal reasons. 2 patients were in the process of neoadjuvant therapy and had not undergone surgery yet. The remaining 7 patients underwent radical surgery and 4 patients (57.14%) achieved pCR (pT0N0M0). The main treatment-related grade 3/4 adverse event (AE) was neutropenia (1/21). All the AEs were manageable. The average intraoperative blood loss was 221mL and the average hospitalization time after operation was 12.7 days (range 8-19 days). No anastomotic leakage and treatment-related death occurred. Conclusions: Camrelizumab in combination with paclitaxel and platinum as a neoadjuvant therapy was well tolerated. The pCR rate of 57.14% was higher than the expected 40%. This encouraging result promoted us to continue this phase Ⅱ study. Clinical trial information: ChiCTR2000033761.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 220-220
Author(s):  
Chao Cheng ◽  
Weixiong Yang ◽  
Wenfang Chen ◽  
Sai-Ching Jim Yeung ◽  
Xiangbin Xing ◽  
...  

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.


2020 ◽  
Vol 62 (1) ◽  
pp. 142-148
Author(s):  
Masanori Ochi ◽  
Yuji Murakami ◽  
Ikuno Nishibuchi ◽  
Katsumaro Kubo ◽  
Nobuki Imano ◽  
...  

Abstract Purpose The present study aimed to evaluate the long-term results of definitive chemoradiotherapy (CRT) for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). Materials and methods We analyzed eighty patients with unresectable LA-ESCC, who underwent definitive CRT between 2001 and 2014. The 5-year overall survival (OS), cause-specific survival (CSS), and progression-free survival (PFS) rates were calculated, and we investigated the prognostic factors and adverse events. Results The median age was 66 years (range, 41–83 years). Histologically, all patients had squamous cell carcinoma. The most common tumor site was the middle thoracic esophagus in 43 (54%) patients. According to the eighth edition of the Union for International Cancer Control TNM classification, sixty-six patients (83%) had T4 disease, 59 (74%) had regional lymph node (LN) metastases, and 35 (44%) had distant LN metastases beyond the regional LN (M1 LYM) disease. Forty-five (56%) and 35 (44%) patients belong to clinical stages IVA and IVB, respectively. The median follow-up period for survivors was 86 months. The 5-year OS, CSS, and PFS rates were 20.2%, 25.7%, and 18.4%, respectively. On univariate analysis, only the performance status score was significantly associated with better overall survival (p = 0.026). Grade 3 or higher late adverse events were observed in 12 (15%) patients, and these included cardiopulmonary adverse events in 6 (8%) patients. Treatment-related death occurred in 3 (4%) patients. Conclusion We showed the long-term results of definitive CRT for unresectable LA-ESCC. The survivals are still poor and new treatment strategies need to be developed.


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