Perioperative chemotherapy alone versus preoperative chemoradiotherapy for locally advanced distal esophageal and gastroesophageal junction cancer: A 10-year review of the British Columbia (BC) Cancer Registry.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4028-4028
Author(s):  
Shiru Lucy Liu ◽  
Irene S. Yu ◽  
Sally CM Lau ◽  
Yizhou Zhao ◽  
Devin Schellenberg ◽  
...  
Keyword(s):  
Cancer Registry ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy ◽  
Pathologic Response ◽  
R0 Resection ◽  
Perioperative Chemotherapy ◽  
Cancer Specific Survival ◽  
Significant Difference

4028 Background: The optimal treatment strategy for resectable cancer of the distal esophagus (ESOPH) and gastroesophageal junction (GEJ) remains controversial. This study evaluates patterns of practice in BC, rates of complete surgical resection, and survival outcomes of patients treated with perioperative chemotherapy alone (CA), per MAGIC or FLOT4 protocol, versus preoperative chemoradiotherapy (CRT), per CROSS protocol. Methods: We undertook a provincial analysis of initially resectable, locally advanced, cancer of the ESOPH and/or GEJ who underwent surgery in BC, from 2008 to 2018. Baseline patient, tumor, treatment, and clinical outcome data were collected from the BC Cancer Registry. Kaplan-Meier survival and multivariate regression analyses were conducted. Results: Among 575 patients, 468 underwent surgery and were included (Table). More surgeries were aborted intraoperatively in the CA cohort compared to CRT (12% vs 2%, p<0.001). There was no difference in age, sex, or ECOG performance status among the cohorts, and 83% were adenocarcinoma. While 82% of ESOPH involving GEJ (N = 251, 54%) is treated with CRT, only 53% of GEJ alone (N=217, 46%) is treated with CRT (p<0.001). CRT is associated with a higher rate of complete or partial pathologic response compared to CA (59% vs 39%, p=0.002). R0 resection rate was 90% and 94% in the CA and CRT cohort, respectively (p=0.383). There is no statistically significant difference in overall survival, with medians of 29.6 and 26.0 months for patients treated with CA and CRT, respectively (p=0.723). Cancer-specific survival is also not significantly different (p=0.565). In the CA cohort, 37% of patients complete all 8 cycles of FLOT and 52% of patients complete all 6 cycles of MAGIC (p=0.396). Conclusions: Patients treated with CRT have higher rates of complete resection and pathologic response, but their survival is not significantly different compared to those treated with CA. [Table: see text]

scholarly journals Duration of Perioperative Chemotherapy in Locally Advanced Gastric Cancer: A “Less Is More” Question When ypN0 Is Achieved

2021 ◽  
Vol 11 ◽  
Author(s):  
Zining Liu ◽  
Yinkui Wang ◽  
Fei Shan ◽  
Xiangji Ying ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Cox Regression ◽  
Locally Advanced ◽  
R0 Resection ◽  
Perioperative Chemotherapy ◽  
Tree Model ◽  
Less Is More ◽  
Locally Advanced Gastric Cancer ◽  
Significant Difference

BackgroundsPerioperative chemotherapy (PEC) and neoadjuvant chemotherapy (NAC) have become a vital part of locally advanced gastric cancer (LAGC) treatment, but the optimal duration of PEC has not been studied. The aim of this study was to demonstrate the possibility of duration reduction in PEC in the adjuvant chemotherapy (AC) phase for ypN0 patients.MethodsWe included LAGC patients who achieved ypN0 after NAC in our institution from 2005 to 2018. The risk/benefit of AC and other covariates were majorly measured by overall survival (OS) and progression-free survival (PFS). We developed a survival-tree-based model to determine the optimal PEC duration for ypN0 patients in different classes.ResultsA total of 267 R0 resection patients were included. There were 55 patients who did not receive AC. The 5-year OS was 74.34% in the non-AC group and 83.64% in the AC group with a significant difference (p = 0.012). Multivariate Cox regression revealed that both AC (AC vs. non-AC: HR, 0.49; 95%CI, 0.27–0.88; p = 0.018) and ypT stages (ypT3-4 vs. ypT0-2: HR, 2.00; 95%CI, 1.11–3.59; p = 0.021) were significant protective/risk factors on patients OS and PFS. A decision tree model for OS indicated an optimal four to six cycles of PEC, which was recommended for ypT0-2N0 patients, while a minimum of five PEC cycles was recommended for ypT3-4N0 patients.ConclusionAC treatment is still necessary for ypN0. The duration reduction could be applied for the ypT0-2N0 stage patients but may not be suitable for higher ypT stages and beyond. A multicenter-based study is required.

Unanswered Questions in the Management of Gastroesophageal Junction Adenocarcinoma: An Overview from the Medical Oncologist's Perspective

2013 ◽  
pp. e155-e159
Author(s):  
Manish A. Shah
Keyword(s):  
Gastric Cancer ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy ◽  
Phase Iii ◽  
Perioperative Chemotherapy ◽  
Two Phase ◽  
Multiple Treatment ◽  
Gastroesophageal Junction Adenocarcinoma

Patients with gastroesophageal junction (GEJ) adenocarcinoma have multiple treatment options; however, are victims of lack of consensus and wide variation in treatment, sometimes within the same hospital. While there is a consensus that surgery alone is inadequate for locally advanced disease, locoregional treatment has become the point for debate. Only in 2010 was the reclassification of GEJ cancers as esophageal cancers. Treatment options remain as varied as the classification of GEJ cancers: preoperative chemoradiotherapy, definitive chemoradiation, perioperative chemotherapy, and resection followed by postoperative chemoradiation. Several studies have examined the varying treatment paradigms; however, many fall short due to methodology or sample size. The MAGIC study determined perioperative chemotherapy to be an acceptable standard treatment option for patients with gastric cancer, althouth a significant portion of enrolled patients had distal esophageal and GEJ adenocarcinoma. The CROSS study concluded combination chemotherapy and radiation before resection beneficial. Preoperative therapy in cases of GEJ is beneficial for survival, but not as much impact is seen as in esophageal SCC, which exhibits an increased sensitivity to CRT. There is concurrence with two phase III studies from Japan and Korea on the role of adjuvant chemotherapy for gastric cancer. However, the applicability of these studies to GEJ adenocarcinoma remains a question, especially with the significantly different epidemiology of increased proximal and GEJ tumors in the West compared to Asia. To move forward with this increasingly prevalent disease, we will need to do more than understand the multiple treatment paradigms—we will need to select a strategy and examine it.

scholarly journals Prognoses in Pathologically Confirmed T1 Lower Rectal Cancer Patients with or without Preoperative Therapy: An Analysis Using the Surveillance, Epidemiology, and End Results Database

Oncology ◽  
2021 ◽  
Author(s):  
Tetsuro Taira ◽  
Hiroaki Nozawa ◽  
Kazushige Kawai ◽  
Kazuhito Sasaki ◽  
Koji Murono ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy ◽  
Preoperative Therapy ◽  
Lower Rectal Cancer ◽  
Cancer Specific Survival ◽  
Factors Associated ◽  
Significant Difference ◽  
Significant Factors ◽  
End Results

Introduction Preoperative chemoradiotherapy (CRT) is the standard therapy for downstaging in locally advanced lower rectal cancer. However, it remains unclear whether rectal cancers down-staged by preoperative therapy show similar prognoses to those of the same stage without preoperative therapy. We previously demonstrated that preoperative CRT did not affect prognosis of rectal cancer with pathological T1N0 (pT1N0) stage in a single institute. Here, using a larger dataset, we compared prognoses of (y)pT1 rectal cancer stratified by the use of preoperative therapy and analyzed prognostic factors. Methods Cases of pT1N0 rectal cancer, registered between 2004 and 2016, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized as the ‘ypT1 group’ if they had undergone preoperative therapy before surgery or as the ‘pT1 group’ if they had undergone surgery alone. overall survival (OS) and cancer-specific survival (CSS) between these groups of patients was compared. Factors associated with CSS and OS were identified by univariate and multivariate analyses. Results Among 3,757 eligible patients, ypT1 and pT1 groups comprised 720 and 3,037 patients, respectively. While ypT1 patients showed poorer CSS than ypT1 patients, there was no significant difference in OS. Preoperative therapy was not an independent prognostic factor for CSS or OS. Multivariate analysis identified age and histological type as significant factors associated with CSS. Sex, age, race, and number of lymph nodes dissected were identified as significant factors associated with OS. Conclusions Prognosis among patients with (y)p T1N0 rectal cancer was similar irrespective of whether they underwent preoperative therapy, which is consistent with our previous observations.

Preoperative chemotherapy plus bevacizumab with early salvage therapy based on FDG-PET response in locally advanced gastroesophageal junction and gastric adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4101-4101
Author(s):  
Geoffrey Yuyat Ku ◽  
David Paul Kelsen ◽  
Vivian E. Strong ◽  
Heiko Schöder ◽  
Yelena Yuriy Janjigian ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Preoperative Chemotherapy ◽  
Salvage Therapy ◽  
Fdg Pet ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Salvage Chemotherapy ◽  
Pet Scan ◽  
R0 Resection ◽  
Significant Difference

4101 Background: Response on FDG-PET scan during preoperative chemotherapy has prognostic significance. We performed a phase II trial to examine the effectiveness of FDG-PET directed early switching to salvage chemotherapy measured by 2-year disease free survival (DFS). Methods: Pts with PET avid, endoscopic ultrasound and laparoscopically staged T3 or N+ resectable gastric or GEJ adenocarcinoma received induction epirubicin 50mg/m2, cisplatin 60mg/m2 Day 1, capecitabine 625mg/m2 BID Days 1-21 (ECX) and bevacizumab 15mg/kg Day 1. PET scan was repeated at Week 3. PET responders (≥35% decline in SUV) continued with ECX for 2 more cycles. PET non-responders were switched to 2 cycles of salvage therapy: docetaxel 30mg/m2 and irinotecan 50mg/m2Days 1 and 8 q21 days and bevacizumab 15mg/kg Day 1. All pts went to surgery 4 weeks after Cycle 3. Results: Twenty of planned 60 pts were enrolled before the study closed for poor accrual. Eleven (55%) had a PET response after induction. Ten of 11 underwent R0 resection: 1/10 path complete response, 3/10 path partial response. Nine PET non-responders were switched to the salvage regimen. Seven of 9 non-responders had R0 resection, none achieved a pathological response. The median DFS for PET responders was 27.8 mos (95% CI 10.3-27.8) and DFS in salvage group has not been reached. There was no significant difference in DFS between the two groups (p= 0.4). Follow up for overall survival is ongoing. Conclusions: Response on PET scan during induction chemotherapy can identify early treatment failures. The results for therapy cross-over indicate a potentially improved DFS with salvage chemotherapy. Results from this trial are hypothesis generating and merit evaluation in a larger clinical trial. Updated survival data will be presented. Clinical trial information: NCT00737438.

Single-institution experience of preoperative chemoradiotherapy for locally advanced gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 99-99
Author(s):  
J. M. Pepek ◽  
J. P. Chino ◽  
C. G. Willett ◽  
D. S. Tyler ◽  
H. E. Uronis ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Radiation Treatment ◽  
Performance Status ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Preoperative Chemoradiotherapy ◽  
Poor Performance Status ◽  
R0 Resection ◽  
Hematologic Toxicity

99 Background: To examine acute toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. Methods: Patients with gastroesophageal (GE) junction (Siewert type II and III) or stomach adenocarcinoma who underwent curative intent CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Tumors were staged according to AJCC 6th edition. Local recurrence was defined as radiographic or biopsy- proven disease within the radiation treatment field. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to CTCAE v4.0. Results: Forty-eight patients (60% stage III, 8% stage IV) were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Thirty-five percent had signet ring histology, 52% had poorly differentiated tumors and 10% had linitis plastica. Median age was 60 years and median RT dose was 45 Gy. All patients received concurrent chemotherapy (CT) with 40 (83%) receiving 5-FU-based CT. Rates of acute > grade 2 hematologic and non-hematologic toxicity were 38% and 10%, respectively. Six patients (13%) required treatment break and two (4%) were unable to complete the prescribed treatment course. Thirty-six patients (75%) underwent surgery. Patients did not undergo surgery due to distant metastases at laparotomy or restaging (n=9), patient refusal (n=2) or poor performance status (n=1). Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS for all patients was 40%. For those undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Conclusions: Preoperative CRT for gastric cancer is reasonably well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with advanced disease, LC, DFS and OS rates in resected patients are comparable to similarly staged, adjuvantly treated historic controls. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated. No significant financial relationships to disclose.

Perioperative chemotherapy in locally advanced gastric cancer in Chile: From evidence to daily practice.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 92-92
Author(s):  
Bettina G. Müller ◽  
Carlos Garcia ◽  
Jose Antonio Sola ◽  
Carlos Benavides ◽  
Patrick Werner ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Public Hospitals ◽  
R0 Resection ◽  
Perioperative Chemotherapy ◽  
Locally Advanced Gastric Cancer ◽  
Informed Consent Form ◽  
Preoperative Ct

92 Background: Gastric cancer is the leading cause of cancer death in Chile, with mortality rate of 26.7/100.000 in men, placing the country among the highest mortality rates worldwide. For locally advanced gastric cancer, a multimodality treatment is recommended, but in Chile, the treatment covered by the public health insurance, which assists more than 70% of the patients, is surgery alone. We conducted an observational study to assess efficacy and toxicity of perioperative chemotherapy (CT) in public hospitals in Chile (NCT01633203). Methods: Patients with locally advanced, operable gastric carcinoma, defined as presence of invasion of serosa or beyond (cT > 3 AJCC 2002) and/or lymph node metastasis (cN+) without distant metastasis (M0), were offered to receive preoperative CT with Epirubicin+Cisplatin+Capecitabine (ECX) regimen for 3 cycles followed by curative surgery with D2 lymphadenectomy. Staging abdominal CT scan was mandatory, laparoscopy was recommended. Patients with gastric retention, severe dysphagia or contraindications for CT were excluded. All patients signed the IRB approved informed consent form prior to enrolment. Data were collected using the OpenClinica platform. Results: Between August 2010 and March 2013, 110 patients were screened and 61 enrolled. Median age was 62 years (23-76 years) and most patients had good performance status at baseline (ECOG 0: 42, ECOG 1: 19). Tumor site was proximal in 24 (39%), medial in 16 (26%) and distal in 10 patients (16%). All but 4 patients (n = 57, 93%) completed three cycles of preoperative CT as planned. Fifty-five patients were operated and 54 (89%) had curative R0 resection. Of these, 36 (67%) had pT0-2, and 15 (28%) had pN0 tumors. A complete pathological response was found in 2 patients. Two patients were not operated for other reasons (one patient refused surgery and one patient presented a cerebrovascular accident during preoperative CT and died), and 5 patients (8%) progressed. As of September 1, 2015, 32 patients died. Three-year survival rate was 49%. Conclusions: Perioperative CT is feasible in public hospitals in Chile and should be offered as an alternative to primary surgery for patients with locally advanced gastric cancer.

Gastric and gastroesophageal adenocarcinoma survival outcomes relative to completion of perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT): A single-center retrospective analysis.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 224-224
Author(s):  
Michael J Allen ◽  
Osvaldo Espin-Garcia ◽  
Elan David Panov ◽  
Lucy Xiaolu Ma ◽  
Chihiro Suzuki ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Performance Status ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Median Number ◽  
Small Population ◽  
Tumour Regression ◽  
World Population ◽  
Perioperative Chemotherapy ◽  
Significant Difference

224 Background: Perioperative FLOT is standard-of-care for locally advanced resectable gastric and gastroesophageal (GEJ) adenocarcinoma. Completion of perioperative chemotherapy (8 cycles) is potentially jeopardised by significant toxicity and intolerance. Only 46% of patients completed all cycles in the initial phase 2/3 trial (FLOT-AIO). We sought to determine the rate of treatment completion in a real-world population and any subsequent impact on survival of incomplete treatment. Methods: A retrospective analysis of gastric and GEJ adenocarcinoma patients treated with perioperative FLOT at Princess Margaret Cancer Centre, Toronto between September 2017 and July 2020 was performed. The rate of perioperative FLOT administration, disease-free survival (DFS) and overall survival (OS) was analysed, with outcomes compared between patients that completed perioperative FLOT and those that didn’t. Results: 32 patients were identified as receiving neoadjuvant FLOT. Mean age was 61.5y, 26 (81%) were male and 29 (91%) were non-Asian. All patients were ECOG 0-1. The median number of neoadjuvant cycles was 4. 29 (91%) had surgery (2 = disease progression; 1 = declined surgery). 10 (34%) patients had minimal/nil response upon resection (College of American Pathologists Tumour Regression Grading (TRG) Score 3), 5 of whom received adjuvant FLOT whilst 5 did not (p0.28). 10 (34%) patients did not receive adjuvant FLOT, 18 (62%) did and 1 received 8 cycles of neoadjuvant chemotherapy. Nil demographic differences were observed between ‘yes’ and ‘no’ adjuvant FLOT groups. The reasons for not having adjuvant chemotherapy were: metastatic disease diagnosed post-operatively (n = 2), TRG Score 3 (n = 4), patient declined further chemotherapy (n = 1), reduced performance status and/or toxicity (n = 2), and the patient requiring treatment for a second malignancy (n = 2). 10 (34%) patients completed perioperative chemotherapy. Median DFS was 12.5m (95% CI 7.9-12.5) for ‘no’ FLOT’ and was not-reached for ‘yes’ FLOT (p = 0.29). 18m DFS was 50% (95% CI 27-93) v 81% (95% CI 64-100) respectively. The median OS for ‘no’ adjuvant FLOT was 16.7m (95% CI 11.5-16.7) with 5 deaths. Zero deaths due to malignancy had occurred at 23.3m in those who received adjuvant FLOT (p0.00164). 1 death in the ‘yes’ group occurred due to interstitial lung disease. Conclusions: In our small population size 34% of patients completed perioperative FLOT. Whilst nil statistically significant difference was observed in mDFS, an improved mOS was observed in those that received adjuvant FLOT suggesting an importance in receiving the maximum number of cycles of chemotherapy. Given the challenges of administering adjuvant FLOT future trials into the feasibility and efficacy of 8 cycles of neoadjuvant FLOT should be considered.

scholarly journals Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer

2015 ◽  
Vol 49 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Ivica Ratosa ◽  
Irena Oblak ◽  
Franc Anderluh ◽  
Vaneja Velenik ◽  
Jasna But-Hadzic ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
External Beam Radiotherapy ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Poor Performance Status ◽  
R0 Resection ◽  
Treatment Schedule ◽  
Preoperative Treatment ◽  
Preoperative Radiochemotherapy

Abstract Background. To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution. Patients and methods. Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4-6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival. Results. Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five patients (5.6% of all treated patients or 8.8% of all operated patients). Down-staging was recorded in 49 patients (86%), in one patient (1.8%) the stage after radiochemotherapy was unchanged while in seven patients (12.3%) the pathological stage was higher than clinical, mainly due to higher pN stage. No death was recorded during preoperative radiochemotherapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression (granulocytopenia). Twentysix (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free at the time of analysis, while 29 patients (50.9%) developed the recurrence, mostly as distant metastases. At two years, locoregional control, diseasefree survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively. Conclusions. Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achieved down-staging, allowing greater proportion of radical resections (R0), which are essential for patients’ cure.

Phase II trial of perioperative chemotherapy + avelumab in locally advanced gastroesophageal adenocarcinoma: Preliminary results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4046-4046
Author(s):  
Thierry Alcindor ◽  
Touhid Opu ◽  
Arielle Elkrief ◽  
Farzin Khosrow-Khavar ◽  
Carmen L. Mueller ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Regression ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Daily Intake ◽  
Disease Free Survival ◽  
Type I ◽  
Perioperative Chemotherapy ◽  
Preliminary Results ◽  
Gastroesophageal Adenocarcinoma

4046 Background: Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of avelumab to perioperative chemotherapy will increase the major pathologic response (MPR) rate in comparison with historical controls. Methods: Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, M0, WHO PS 0-1. Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II gastroesophageal junction (GEJ) tumors. Aim of the study: MPR as defined as tumor regression grades 0-1 (modified Ryan scheme); as per hypothesis, this experimental regimen will result in a 20% rate of MPR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 MPR are seen in the first 16 patients, the study will be closed. The study hypothesis cannot be rejected if at least 6 MPR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle. Survival rates are calculated with Kaplan-Meier method. Preliminary results are presented since the study has met its primary endpoint. Results: Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: GEJ (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Biomarkers expression: mismatch repair (MMR) protein loss (3/28); PD-L1(clone 73-10) expression in 1% (TPS) or more of tumor cells seen in 12/28 samples, and >10% in 6 patients. Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show MPR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions. No correlation was seen between MMR proteins or PD-L1 expression and tumor regression. With a median follow-up of 1.5 years (range 0.4-2.5), the disease-free survival rate is projected to be 0.92 (95% CI 0.83-1.00) at 12 months and 0.77 (95% CI 0.58-1.00) at 24 months. Conclusions: The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment. Clinical trial information: NCT03288350.

740 CAMRELIZUMAB IN COMBINATION WITH PREOPERATIVE CHEMOTHERAPY FOR LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A SINGLE-ARM, OPEN-LABEL, PHASE II STUDY

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Yu Qi ◽  
Xiangrui Meng ◽  
Qingxia Fan
Keyword(s):  
Phase Ii ◽  
Preoperative Chemotherapy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Reduction Rate ◽  
Complete Response ◽  
Pathologic Response ◽  
R0 Resection ◽  
Efficacy And Safety

Abstract   At present, ESCC has a dismal prognosis with huge unmet clinical needs. With the potential benefit of combining PD-1 inhibitor with nCT, we conducted a phase II trial to assess the efficacy and safety of Camrelizumab plus nCT for locally advanced ESCC. Methods 45 patients (pts) with histologically confirmed stage II/III/IVa(cT2-4aN0-3 M0) ESCC were enrolled from February 2020 to March 2021.The study was divided into two stages, stage1: we administered 1 cycle of Camrelizumab for induction therapy (200 mg q2 weeks); stage2: pts received 2 cycle of Camrelizumab (200 mg every 3 weeks) plus docetaxel and nedaplatin, followed by surgery within 4 ~ 6 weeks after neoadjuvant therapy completion. Primary endpoint was major pathologic response (MPR). Secondary endpoints included pathologic complete response (pCR), R0 resection rate, disease-free survival (DFS) and overall survival (OS). Results At the cutoff date of Mar 9, 2021, 45 eligible pts were enrolled, neoadjuvant treatment was completed in 39 pts. Thus far 32 pts were resected, all patients underwent an R0 resection. Postoperative pathology showed that TNM stage decreased in 28 pts with 87.5% reduction rate. 19 pts (59.38%) reached major pathologic response, 9 pts (28.13%) reached pathologic complete response (no surgery related mortality). A total of 75.56% had AEs with 13.33% of grade ≥ 3 AEs. Date for median DFS and OS were not matured. Conclusion Camrelizumab in combination with preoperative chemotherapy followed by surgery for locally advanced ESCC showed promising downstaging effect and MPR with good tolerance, and its efficacy and safety could be further studied in later trials. Clinical trial information: NCT03917966.

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