Neoadjuvant Therapy With Nab-paclitaxel and Cisplatin for Locally Advanced Esophageal Squamous Cell Carcinoma

2019 ◽  
Author(s):  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Locally Advanced

Phase-II study of toripalimab combined with neoadjuvant chemotherapy for the treatment of resectable esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16029-e16029
Author(s):  
Delin Liu ◽  
Qin Zhang ◽  
Jinghua Zhu ◽  
Ting Qian ◽  
Rong Yin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Radiochemotherapy ◽  
Grade 3

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.

Camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESPRIT): A phase Ⅱ, single-arm, exploratory research.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16033-e16033
Author(s):  
Jianqun Ma ◽  
Jinfeng Zhang ◽  
Yingnan Yang ◽  
Dayong Zheng ◽  
Xiaoyuan Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Radical Surgery ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Therapeutic Effects

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.

Molecular characterization of amplification of 11q13 region in patients with operable esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16053-e16053
Author(s):  
Shuoyan Liu ◽  
Feng Wang ◽  
Peiyuan Wang ◽  
Yujie Chen ◽  
Peng Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Molecular Characterization ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Genomic Amplification ◽  
11Q13 Amplification

e16053 Background: The efficacy of programmed cell death 1 (PD-1) targeted therapy had showed effective treatment in patients (pts) with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). Meanwhile some studies have shown that PD-1 as neoadjuvant therapy showed promising anti-tumor activity with acceptable tolerance for locally advanced ESCC. Previous studies have shown genomic amplification of 11q13 region may serve as a negative predictive marker for ESCC patients receiving anti-PD-1 based immunotherapy. However, related molecular characterization study of amplification of 11q13 region in patients with operable ESCC is rare reported. Methods: The study recruited pts with operable ESCC whose tissues were send to perform target-capture deep sequencing with the pan-cancer panel and immunohistochemistry of PD-L1 with 22C3 assay. Pair-wise comparison of TMB and PD-L1 was analyzed in pts with 11q13 amplification and pts without 11q13 amplification. Results: 58 operable ESCC pts (cT1-T3N0) were enrolled, median age at diagnosis was 63 years(yrs) (45-73). Copy number analysis identified 30 out of 58 (52%) patients with amplifications of four genes located in chromosome 11q13 region, including CCND1(Cyclin D1) and fibroblast growth factor family members ( FGF3/4/19). Among the 11q13 amplification cohort, four genes amplified together were occurred in 27(90%) pts, 1(3%) patient had amplification of three genes ( CCND1 and FGF3/4), 2 (7%) pts had amplification of one gene that are FGF3 and CCND1 respectively. The prevalence rate of 11q13 amplification was not significantly different between older age (≥ 63 yrs) and young age ( < 63 yrs). Among 58 pts with TMB evaluated, median TMB was 5.76 muts/Mb (range: 0 - 20.16 muts/Mb). The prevalence of TMB-H and microsatellite instability was 12% (7/58) and 0% (0/58). TMB and expression of PD-L1 showed no significantly difference between 11q13 amplification cohort and 11q13 wild cohort. The most frequently mutated genes were TP53 (96.7%, 29/30 pts), NOTCH1 (33.3%, 10/30 pts), CDKN2A (23.3%, 7/30 pts) and MLL2 (20%, 6/30 pts) in 11q13 amplification cohort, while TP53 (89.3%, 25/28), NOTCH1 (39.3%,11/28), MLL2 (28.6%, 8/28), FAT1 (25%,7/28) were the most frequently mutated genes in 11q13 wild cohort. Conclusions: Amplification of 11q13 region was a high prevalence event in operable ESCC and there was show no age bias. Molecular characterization of amplification of 11q13 region in patients receiving PD-1 as neoadjuvant therapy before surgery may be meaningful.

Neoadjuvant camrelizumab combined with chemotherapy and apatinib for locally advanced thoracic esophageal squamous cell carcinoma (ESCC): A single-arm, open-label, phase Ib study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4047-4047
Author(s):  
Zhen Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
End Points ◽  
Grade 3

4047 Background: Neoadjuvant therapy with PD-1 blockade plus chemotherapy has been found to be effective in the first-line treatment of advanced esophageal cancer. However, evidence of PD-1 blockade combined with chemotherapy as neoadjuvant treatment is limited. This study was designed to investigate the safety and efficacy of camrelizumab, a PD-1 blockade combined with chemotherapy and apatinib as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: A regiment of 2–4 cycles of neoadjuvant camrelizumab (200 mg, intravenous, day 1), nab-paclitaxel (150 mg/m2, intravenous, day 1), nedaplatin (50 mg/m2, intravenous, day 1), and apatinib (250 mg, orally, day 2–4) was given to the treatment-naive patients with resectable locally advanced ESCC. The treatments were repeated every 14 days. In this study, six patients were planned to receive two cycles of neoadjuvant therapy as safety assessment, and then 24 patients received four cycles of neoadjuvant therapy, followed by esophagectomy after 4–8 weeks. The primary end points were safety and feasibility. The secondary end points were the rate of major pathologic response (MPR) and pathologic complete response rate (pCR). Results: A total of 30 patients were enrolled, among them, five patients received two planned cycles of neoadjuvant therapy, and one patient missed the second cycle of therapy due to grade 3 ALT elevations. Further, all other 24 patients received four planned cycles of neoadjuvant therapy. A total of 11 patients (11/30, 36.7%) experienced grade 3 neoadjuvant treatment-related adverse events (TRAEs). No grade 4 and grade 5 TRAEs were reported. The most frequent grade 3 TRAEs was neutropenia (7/30, 23.3%). Twenty-nine patients underwent minimally invasive esophagectomy (McKeown procedure) after neoadjuvant therapy. The reason for not undergoing surgery was due to bone metastasis. There were five treatment-related surgical delays that were caused by adverse reactions (hyperglycemia, arthritis, anemia, leukopenia, capillary endothelial proliferation in oral mucosa). Among the 29 patients undergoing esophagectomy, 15 patients (15/29, 51.7%) achieved MPR, including 7 patients with pCR (7/29, 24.1%). Among the 24 patients who received four cycles of neoadjuvant treatment, there were 7 patients with pCR (7/24, 29.2%), and 14 patients with MPR (14/24, 58.3%). No surgery related mortality was documented. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy plus apatinib is a safe and tolerable treatment for patients with locally advanced ESCC, and the MPR and pCR rate are promising. Clinical trial information: ChiCTR1900023880.

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 ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Pilot Study ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Locally Advanced ◽  
R0 Resection ◽  
Resection Rate

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.

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