FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF therapy for locally advanced esophageal carcinoma (JCOG1804E)—The short-term results of cohort A and B.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 202-202
Author(s):  
Shun Yamamoto ◽  
Ken Kato ◽  
Hiroyuki Daiko ◽  
Takashi Kojima ◽  
Hiroki Hara ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Tnm Classification ◽  
Clinical Stage ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Cytotoxic Agents ◽  
Feasibility Trial ◽  
R0 Resection ◽  
Breast Cancers

202 Background: The standard neoadjuvant chemotherapy (NAC) in Japan for locally advanced esophageal squamous cell cancer (ESCC) is CDDP + 5-FU (CF). Immune checkpoint inhibitors (ICI) such as nivolumab provide a survival benefit in ESCC, and have potential as NAC agents in lung, skin, and breast cancers, amongst others. However, whether ICI are efficacious in combination with cytotoxic agents, and whether ICI impact the safety of subsequent surgery after they are used as NAC for ESCC patients (pts) is currently unclear. Methods: FRONTiER is a multi-cohort phase I study designed to evaluate the safety and efficacy of ICI combined with NAC in ESCC. Histologically proven ESCC pts with cT1N1-3M0 or cT2-3N0-3M0 (8th-UICC TNM classification), 20–75 years old, PS ≤ 1, no prior therapies against any cancer were eligible. The primary endpoint was the incidence of dose-limiting toxicities (DLT) from the initial dose to the 30th postoperative day. This study contained 4 experimental cohorts, the NAC regimen of cohort A consisted of 2 courses of CDDP at 80 mg/m2, nivolumab at 360 mg/body on day 1 and 5-FU at 800 mg/m2 on days 1–5, q3wks. The regimen of cohort B consisted of one administration of nivolumab at 240 mg/body 2 weeks before chemotherapy, followed by the same treatments as cohort A. Results: Thirteen pts were enrolled to cohort A (n = 6) and B (n = 7). Characteristics were follows; median age: 62 (range: 34–75), PS 0/1: 9/4 pts, clinical stage I/II/III: 2/1/10 pts. One pt in cohort B was excluded from safety evaluation due to R2 resection, no DLTs were observed in 12 pts. The most frequent adverse events (≥ grade 3) were neutropenia in 6 pts during NAC, lung infection in 1, hyperglycemia in 1, pleural effusion in 1, infection (right neck) in 1, anemia in 1, abdominal pain in 1, and anatomic leakage in 1 during the postoperative period. Within 30 days post-operation, grade 2 adrenal insufficiency was observed in 1 pt of cohort B. No grade 4 adverse events or treatment-related deaths were seen. All pts received two courses of NAC + nivolumab and R0 resection was achieved in 12 pts (92.3%) without interruption of treatment. A pathological complete response was achieved in 2 pts (33.3%) in cohort A. Conclusions: Neoadjuvant CF + nivolumab with/without prior administration of nivolumab followed by surgery for locally advanced ESCC was well tolerated and showed promising efficacy. Clinical trial information: NCT03914443.

624 A PHASE III STUDY ON NEOADJUVANT TORIPALIMAB PLUS CHEMOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY FOR LOCALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yan Zheng ◽  
Jiangong Zhang ◽  
Wenqun Xing
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
R0 Resection ◽  
Phase Iii Trial ◽  
Free Survival

Abstract   In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in our Hospital. Methods A two-arm phase III trial was launched in April 2020 in our Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Results Until Dec. 2021, one hundred and twenty ESCC patients recruited in the trial. The trial is ongoing. Conclusion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.

Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4050-4050
Author(s):  
Hongli Li ◽  
Jingyu Deng ◽  
Shaohua Ge ◽  
Fenglin Zang ◽  
Le Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Death Receptor ◽  
Disease Free Survival ◽  
Complete Response ◽  
R0 Resection ◽  
Combination Regimen

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

Phase I Trial of Capecitabine and Weekly Irinotecan in Combination With Radiotherapy for Neoadjuvant Therapy of Rectal Cancer

2005 ◽  
Vol 23 (7) ◽  
pp. 1350-1357 ◽  
Author(s):  
Ralf-Dieter Hofheinz ◽  
Bolko von Gerstenberg-Helldorf ◽  
Frederik Wenz ◽  
Ulrike Gnad ◽  
Uta Kraus-Tiefenbacher ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase I ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Residual Tumor ◽  
Advanced Rectal Cancer ◽  
R0 Resection ◽  
Phase Ii Trials ◽  
Grade 3

Purpose To establish the feasibility and efficacy of capecitabine in combination with weekly irinotecan (CAPIRI) with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer. Patients and Methods Nineteen patients with rectal cancer clinical stage T3-4, Nx received weekly irinotecan 50 mg/m2 (days 1, 8, 15, 22, 29) and two doses of capecitabine (days 1 through 38; dose level [DL] I, 500 mg/m2 bid; DL II, 625 mg/m2 bid) according to phase I methodology. Three-dimensional conformal RT was given to a dose of 50.4 Gy (45 Gy + 5.4 Gy). Results On DL I, no dose-limiting toxicities occurred, whereas diarrhea grade 3 affected three of seven patients on DL II. Twelve patients were treated on DL I and received a median relative dose-intensity of 100% for both drugs. Grade 3 or 4 adverse events were observed in only one of these patients (asthenia grade 3). All patients underwent surgery and R0 resection was achieved in all patients. Pathologic complete remission was observed in four patients and another five patients had only microfoci of residual tumor. Conclusion Preoperative chemoradiotherapy with CAPIRI is feasible and well tolerated. The preliminary efficacy is good, and the tolerability is at least comparable with data for fluorouracil plus irinotecan chemoradiotherapy. Larger phase II trials of the CAPIRI-RT schedule clearly are warranted.

scholarly journals Recent progress in multidisciplinary treatment for patients with esophageal cancer

Surgery Today ◽  
2019 ◽  
Vol 50 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Masayuki Watanabe ◽  
Reiko Otake ◽  
Ryotaro Kozuki ◽  
Tasuku Toihata ◽  
Keita Takahashi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Checkpoint Inhibitors ◽  
Minimally Invasive Esophagectomy ◽  
Clinical Stage ◽  
Multidisciplinary Treatment ◽  
Locally Advanced ◽  
Early Esophageal Cancer ◽  
Long Term Outcome ◽  
Invasive Esophagectomy ◽  
Less Invasive

Abstract Esophageal cancer is one of the most aggressive gastrointestinal cancers. This review focuses on eight topics within the multidisciplinary approach for esophageal cancer. As esophagectomy is highly invasive and likely to impair quality of life, the development of less invasive strategies is expected. Endoscopic resection (ER) of early esophageal cancer is a less invasive treatment for early esophageal cancer. A recent phase II trial revealed that combined ER and chemoradiotherapy (CRT) is efficacious as an esophagus-preserving treatment for cT1bN0 squamous cell carcinoma (SCC). Esophagectomy and definitive CRT are equally effective for patients with clinical stage I SCC in terms of long-term outcome. For locally advanced resectable cancers, multidisciplinary treatment strategies have been established through several clinical trials of neoadjuvant or perioperative treatment. Minimally invasive esophagectomy may improve the outcomes of patients and CRT is a curative-intent alternative to esophagectomy. CRT with 50.4 Gy radiotherapy combined with salvage surgery is a promising option to preserve the esophagus. Induction chemotherapy followed by esophagectomy may improve the outcomes of patients with locally advanced unresectable tumors. Immune checkpoint inhibitors are effective for esophageal cancer, and their introduction to clinical practice is awaited.

Phase I trial of neoadjuvant concurrent chemoradiotherapy with S-1 and weekly irinotecan in locally advanced rectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14543-14543
Author(s):  
J. Ahn ◽  
H. Choi ◽  
S. Cheon ◽  
S. Shin ◽  
K. Keum ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase I ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
R0 Resection ◽  
Dose Levels

14543 Background: S-1 is a novel, orally administered 5-FU analogue and is known of radiosensitizer. The aim of this study was to establish the feasibility and efficacy of S-1 in combination with weekly irionotecan with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer. Methods: Clinical stage T3–4 or N+(on MRI) rectal adenocarcinoma patients received weekly irinotecan 40mg/m2(day1,8,15,22,29) and S-1 at dose levels of 40, 50, 60 and 70mg/m2 (5days a week from day 1 to 38) according to phase I methodology. Concurrently conventional RT was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 50.4 (45 + 5.4)Gy. Surgery was performed 4–8 weeks following completion of chemoradiation. Results: A total 16 patients (10M/7F, median age 46 years, ECOG PS0–1) were enrolled between August 2005 and July 2006. One pt withdrew the consent during CCRT. Dose-limiting toxicity (DLT) occurred at 50mg/m2 of S-1 in one of six pts (G4 cerebral infarction). At dose of 60, 70mg/m2 of S-1, no DLT occurred. G3/4 toxicties were rare. Fifthteen pts underwent surgery and R0 resection was achieved in 13 pts. Four pts (25.0%) had a pathological complete response. Conclusions: The recommended dose (RD) for further study is S-1 70mg/m2 with irinotecan and radiotherapy. Neoadjuvant S-1/irinotecan/RT is feasible and well tolerated. Phase II trial is being conducted. No significant financial relationships to disclose.

Neoadjuvant treatment of primary inoperable or local recurrent thymoma with octreotide LAR to improve tumor resectability.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7105-7105 ◽  
Author(s):  
Berthold Schalke ◽  
Sandra Boy ◽  
Hans-Stefan Hofmann ◽  
Philipp Stroebel ◽  
Joerg Marienhagen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Multiple Testing ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Radical Resection ◽  
R0 Resection ◽  
Open Label ◽  
Multiple Testing Procedure ◽  
Term Survival ◽  
Octreotide Lar

7105 Background: The therapeutic outcome for unresectable, locally advanced, malignant thymoma is poor. Most important factor for long-term survival in thymoma patients is complete resection (R0) of the tumor. The study was performed to evaluate the efficacy of octreotide LAR plus prednisone in patients with primary inoperable or local recurrent thymoma to reduce tumor size. Methods: This was an open label, single-arm study in patients with inoperable or local recurrent thymoma. Patients were considered unlikely to achieve R0 resection at enrollment. Octreotide LAR was administered once every 2 weeks in combination with prednisone. Two stages were planned according to Fleming’s one sample multiple testing procedure for phase II clinical trials. The objective of the study was to show that octreotide LAR is effective in this patient population with respect to tumor shrinkage. Response was defined as decrease in tumor volume of at least 20% at month 3 as compared to baseline. Results: 17 thymoma patients at Masaoka stage III were recruited. Octreotide LAR showed a response in 15 of 17 patients (88.24%) at week 12. Two patients had discontinued the study before week 12 due to unsatisfactory therapeutic effect or adverse events. At Week 12, 5 patients (29.41%) operable for radical resection. 10 patients (58.82%) were not operable for radical resection. 16 of 17 patients (94.12%) experienced adverse events (AEs). The most frequent AEs were gastrointestinal disorders (70.59%), infections and infestations (64.71%), and blood/lymphatic system disorders (41.18%). Conclusions: Octreotide LAR was shown to be effective in patients with inoperable thymoma with respect to tumor shrinkage.Octreotide LAR was generally well tolerated. The reported AEs are in accordance with the known safety profile.

Safety and efficacy of durvalumab following multimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Results from Big Ten Cancer Research Consortium study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4058-4058 ◽  
Author(s):  
Hirva Mamdani ◽  
Bryan J. Schneider ◽  
Laith I. Abushahin ◽  
Thomas J Birdas ◽  
Kenneth Kesler ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Median Number ◽  
R0 Resection ◽  
Big Ten ◽  
Trimodality Therapy ◽  
Surgical Specimen ◽  
Safety And Efficacy ◽  
Distant Relapse

4058 Background: Concurrent chemoradiation (CRT) followed by esophagectomy is a standard of care for locally advanced esophageal (LA-EAC) and GEJ adenocarcinoma. Approximately 50% of patients (pts) experience disease relapse within the 1st yr after treatment(tx) completion. No adjuvant tx has been shown to improve survival in these pts. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown upregulation of PD-1/PD-L1 pathway with RT +/- chemotherapy. Methods: We conducted a phase II trial evaluating safety and efficacy of durvalumab (durva), a monoclonal antibody against PD-L1, in pts with LA-EAC and GEJ adenocarcinoma who have viable tumor in surgical specimen after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1yr. Results: 24 pts were enrolled from 4/2016-1/2018 (median age: 60yrs (range, 43-70). 18 received carbo/paclitaxel and 6 received cis/5-FU concurrently with radiation. Staging at diagnosis: T2N0 (n=3, 12.5%), T2N2 (n=3, 12.5%),T3N0 (n=6, 25%), T3N1 (n=6, 25%), T3N2 (n=4, 17%), T3N3 (n=1, 4%), T3Nx (n=1, 4%).19 pts (79%) had positive lymph nodes (LNs) at the time of surgery following CRT. 12 pts completed 1yr of tx, 12 came off tx before 1yr because of relapse(6), AEs(5), and consent withdrawal (1). Median number of tx cycles was 12.5 (range, 2-13). Most common AEs were fatigue (n=8, 33.3%) and nausea (n=6, 25%). 3pts (12.5%) developed grade 3 irAEs: pneumonitis (1), hepatitis (1), colitis (1). At median follow up of 14.5 mo (range, 1.7-24mo), 17 are disease free (including 5 who came off tx before 1yr). 7pts (29%) have relapsed (3 alive, 4 died). 6/7pts had distant relapse (lung, brain, bone, cervical LNs) and 1 had locoregional relapse. 1-yr RFS and OS were 79.2% and 95.5%, respectively. 2-yr OS was 59.2%. RFS probability at 26 mo was 67.9%. Median survival after relapse was 11.1 mo (range, 0.1-11.3mo). Conclusions: Adjuvant durvalumab following trimodality therapy for LA-EAC and GEJ adenocarcinoma was safe and feasible with improvement in 1-yr RFS to 79.2% compared to historical rate of 50%. OS results are encouraging in this high risk pt population. Clinical trial information: NCT02639065.

A phase I study evaluating COM701 in patients with advanced solid tumors.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. TPS40-TPS40
Author(s):  
Drew W. Rasco ◽  
Kyriakos P. Papadopoulos ◽  
Adeboye H. Adewoye ◽  
John Hunter ◽  
Denise Ramsey ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Adverse Events ◽  
Solid Tumors ◽  
Outcome Measures ◽  
Standard Therapy ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Secondary Outcome ◽  
Tumor Growth Inhibition ◽  
Single Subject

TPS40 Background: Novel checkpoint therapies are needed for the treatment of patients who relapse/refractory to treatment with checkpoint inhibitors. COM701 is a novel first-in-class humanized IgG4 monoclonal antibody that binds with high affinity to poliovirus receptor related immunoglobulin domain containing (PVRIG) blocking its interaction with it's ligand, PVRL2. We have demonstrated in preclinical experiments that inhibition of PVRIG leads to activation of T cells in the tumor microenvironment generating an anti-tumor immune response leading to tumor growth inhibition. We hypothesize that COM701 will be safe and tolerable and demonstrate antitumor activity in pts with R/R solid tumors. Methods: NCT03667716 is an ongoing open-label first-in-human phase 1 study in pts with R/R solid tumors. The initial part of this study will evaluate the safety and tolerability of escalating doses of COM701 monotherapy IV Q3 weekly. Key Inclusion Criteria: Age ≥18 yrs, histologically or cytologically confirmed, locally advanced or metastatic solid malignancy and has exhausted all the available standard therapy or is not a candidate for the available standard therapy, ECOG performance status 0-1, prior anti-PD-1, anti-PD-L1, anti-CTLA-4, OX-40, CD137. Key Exclusion Criteria: Active autoimmune disease requiring systemic therapy in the last 2 years prior to the first dose of COM701, symptomatic interstitial lung disease or inflammatory pneumonitis, untreated or symptomatic central nervous system metastases. Primary outcome measures are the incidence of adverse events and dose-limiting toxicities (21-day DLT window), pharmacokinetics of COM701 and to identify the maximum tolerated dose and/or the recommended dose for expansion. Secondary outcome measures are to characterize the immunogenicity and preliminary antitumor activity of COM701. Study Design: Accelerated titration design consisting of single subject cohorts has been implemented for the initial cohorts. Statistical Considerations: Adverse events graded as per CTCAE v4.03, responses as per RECIST v1.1. The analyses of all study objectives will be descriptive and hypothesis generating. As of the date of this submission a third single subject dose cohort has been filled.

Safety and efficacy of durvalumab following trimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Early efficacy results from Big Ten Cancer Research Consortium study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Hirva Mamdani ◽  
Bryan J. Schneider ◽  
Laith I. Abushahin ◽  
Thomas J Birdas ◽  
Kenneth Kesler ◽  
...  
Keyword(s):  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Primary Objective ◽  
R0 Resection ◽  
Big Ten ◽  
Trimodality Therapy ◽  
Safety And Efficacy ◽  
Research Consortium

5 Background: The standard of care for locally advanced esophageal adenocarcinoma(LA-EAC) is concurrent chemoradiation (CRT) followed by esophagectomy. Approximately 30% of patients (pts) achieve complete pathologic response (pCR) with this approach. The risk of relapse in the remaining 70% of pts is high, with 1-yr relapse free survival (RFS) of 50%. No adjuvant therapies have been shown to improve survival. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown upregulation of PD-1 pathway with radiation +/- chemotherapy. Methods: We conducted a phase II study evaluating safety and efficacy of durvalumab (durva), a monoclonal antibody against PD-L1, in pts with LA-EAC and GE junction (GEJ) adenocarcinoma who do not achieve pCR after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1 yr after surgery. Primary objective was 1-yr RFS. Secondary objectives were incidence and severity of treatment related adverse events (AEs). Results: Twenty-four pts were enrolled from Apr 2016 to Jan 2018 (median age: 60yrs (range, 43-74)). Fourteen pts had GEJ adenocarcinoma and 10 had distal EAC. Eighteen received carboplatin/paclitaxel and six received cisplatin/5-FU concurrently with 50-50.4Gy radiation. Nineteen pts (79%) had positive lymph nodes at the time of surgery after neoadjuvant CRT, including three (12.5%) with N3, nine (37.5%) with N2, and seven (29%) with N1 disease. Among N0 pts, two had T3N0, one had T2N0, and two had T1N0 disease. At median follow-up of 11.7 mo (range 1.7-23.9 mo), seven pts (29%) have relapsed (five alive, two died); 17(67%) are disease free (six on treatment, seven completed treatment, three off-treatment); 1-yr and projected 26 mo RFS are 78.6% and 62.9%, respectively. Five pts (20.8%) developed grade 3 AEs: diarrhea (n = 1), hepatitis (n = 1), encephalopathy (n = 1), hyperglycemia (n = 1), hypoglycemia (n = 1). Most common grade 1 and 2 AEs were fatigue (33.3%), nausea (25.0%), and cough (20.8%). Conclusions: Adjuvant durva in pts with residual disease following trimodality therapy for EAC and GEJ adenocarcinoma is safe and feasible with 1-yr RFS of 78.6% compared to historical rate of 50%. Clinical trial information: NCT02639065.

Camrelizumab combined with FOLFOX as neoadjuvant therapy for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4536-4536
Author(s):  
Ying Liu ◽  
Guangsen Han ◽  
Hongle Li ◽  
Yuzhou Zhao ◽  
Jing Zhuang ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Complete Response ◽  
R0 Resection ◽  
Radical Gastrectomy ◽  
Imaging Evaluation ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Ecog Ps

4536 Background: Neoadjuvant chemotherapy has been demonstrated to improve the pathological complete response(pCR) and 5-year survival rate of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC). Immunotherapy has become a new promising treatment for advanced GC/GEJC. Therefore, we intended to evaluate the safety and efficacy of Camrelizumab (anti-PD-1 antibody) combined with FOLFOX as the neoadjuvant therapy for patients with locally advanced GC/GEJC. Methods: Eligiblepatients were locally advanced GC/GEJC with clinical stage≥T2 and/or positive lymphoglandula confirmed by endoscopic ultrasonography (EUS) and imaging. They received 4 cycles neoadjuvant therapy which including Camrelizumab(200mg ivgtt D1), FOLFOX(Oxaliplatin 85mg/m2 ivgtt D1, 5-Fu 400mg/m2 iv D1, LV 200mg/m2 ivgtt D1, 5-Fu 2.4mg/m2 CIV 46 hours) every 14 days. Imaging evaluation was performed in 2-4 weeks after neoadjuvant therapy. Patients without progression disease (PD) received D2 radical gastrectomy. The primary endpoint was pCR, the secondary endpoints were R0 resection rate and safety. Results: From July 24 2019 to January 31 2020, 16 patients were eligible. The median age was 57 years (29-72 years). A total of 11(69%) males and 5(31%) females, ECOG PS 0 (n=9, 56%), ECOG PS 1 (n=7, 44%). All the patients completed 4 cycles treatment and none of them was confirmed PD by image. One of the patients refused gastrectomy and withdraw from the study. The other 15 patients underwent operation. Unfortunately, intraperitoneal metastases were confirmed in 2 patients during operation. 13 patients received D2 radical gastrectomy and all of them experienced R0 resection. Among the 13 evaluable patients, 1 patient (8%) was observed pCR, 3 patients (23%) experienced TRG1, 10 patients (77%) achieved stage reduction. Notably, 8 patients (62%) had lymphonodus pCR. The grade 3-4 treatment-related AEs were neutropenia (n=3, 19%), leukopenia (n=2, 13%) and anorexia (n=1, 6%). No serious AEs resulted in termination of treatment. Either severe immune-related AEs or treatment-related death was not observed. Conclusions: Camrelizumab combined with FOLFOX as neoadjuvant regimen in patients with locally advanced GC/GEJC showed promising pCR with good tolerance. Clinical trial information: NCT03939962 . [Table: see text]

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