1381P Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): 14-month follow-up of CheckMate 577

2021 ◽  
Vol 32 ◽  
pp. S1045-S1046
Author(s):  
M. Moehler ◽  
J.A. Ajani ◽  
J. Kuzdzal ◽  
T. Zander ◽  
E. Van Cutsem ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Gastroesophageal Junction Cancer

scholarly journals Chemoradiotherapy Using Carboplatin plus Paclitaxel versus Cisplatin plus Fluorouracil for Esophageal or Gastroesophageal Junction Cancer

Oncology ◽  
2020 ◽  
Vol 99 (1) ◽  
pp. 49-56
Author(s):  
Di Maria Jiang ◽  
Hao-Wen Sim ◽  
Osvaldo Espin-Garcia ◽  
Bryan A. Chan ◽  
Akina Natori ◽  
...  
Keyword(s):  
Cox Regression ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Sensitivity Analyses ◽  
Trimodality Therapy ◽  
Gastroesophageal Junction Cancer ◽  
Kaplan Meier

<b><i>Background:</i></b> Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. <b><i>Methods:</i></b> A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. <b><i>Results:</i></b> Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (<i>n</i> = 67; 72%) or dCRT (<i>n</i> = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; <i>p</i> = 0.001; HR 3.1; 95% CI: 1.2–7.7) and DFS (0 vs. 41%; <i>p</i> = 0.004; HR 3.6; 95% CI: 1.4–8.9) on multivariable and IPTW sensitivity analyses. <b><i>Conclusions:</i></b> TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.

scholarly journals A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data

2019 ◽  
Vol 23 (3) ◽  
pp. 510-519 ◽  
Author(s):  
Li-Tzong Chen ◽  
Taroh Satoh ◽  
Min-Hee Ryu ◽  
Yee Chao ◽  
Ken Kato ◽  
...  
Keyword(s):  
Placebo Group ◽  
Gastroesophageal Junction ◽  
Phase 3 ◽  
Double Blind ◽  
Term Survival ◽  
Gastroesophageal Junction Cancer ◽  
Programmed Death ◽  
Previously Treated

Abstract Background Nivolumab showed improvement in overall survival (OS) in ATTRACTION-2, the first phase 3 study in patients with gastric/gastroesophageal junction (G/GEJ) cancer treated with ≥ 2 chemotherapy regimens. The 2-year follow-up results of ATTRACTION-2 are presented herein. Methods ATTRACTION-2 was a randomized, double-blind, placebo-controlled, phase 3 trial (49 sites; Japan, South Korea, and Taiwan). The median (min–max) follow-up period was 27.3 (24.1–36.3) months. The primary endpoint was OS. A subanalysis of OS was performed based on best overall response and tumor-programmed death ligand-1 (PD-L1) expression status. Results Overall, 493 of 601 screened patients were randomized (2:1) to receive nivolumab (330) or placebo (163). OS (median [95% confidence interval; CI]) was significantly longer in the nivolumab group (5.26 [4.60–6.37] vs 4.14 [3.42–4.86] months in placebo group) at the 2-year follow-up (hazard ratio [95% CI], 0.62 [0.51–0.76]; P < 0.0001). A higher OS rate was observed in the nivolumab vs placebo group at 1 (27.3% vs 11.6%) and 2 years (10.6% vs 3.2%). The OS benefit was observed regardless of tumor PD-L1 expression. Among patients with a complete or partial response (CR or PR) in the nivolumab group, the median OS (95% CI) was 26.6 (21.65—not applicable) months; the OS rates at 1 and 2 years were 87.1% and 61.3%, respectively. No new safety signals were identified. Conclusions Nivolumab treatment resulted in clinically meaningful long-term improvements in OS in patients with previously treated G/GEJ cancer. The long-term survival benefit of nivolumab was most evident in patients with a CR or PR.

Pattern of local-regional relapse and survival after bimodality therapy for esophageal cancer: Implications for the surveillance strategy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4083-4083 ◽  
Author(s):  
Kazuki Sudo ◽  
Lianchun Xiao ◽  
Roopma Wadhwa ◽  
Takashi Taketa ◽  
Mariela A. Blum ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Distant Metastases ◽  
Rank Test ◽  
Evidence Based ◽  
Test Results ◽  
Surveillance Strategy ◽  
Gastroesophageal Junction Cancer ◽  
Kaplan Meier ◽  
Regional Disease

4083 Background: Evidence for definitive chemoradiotherapy (bimodality therapy [BMT]) has been established for patients with esophageal and gastroesophageal junction cancer (EGEJC) who do not qualify for surgery. Surveillance for these patients is often recommended but the literature lacks guidance for an evidence-based surveillance strategy after BMT. Methods: We analyzed 276 patients with EGEJC who underwent BMT and had pre- and postchemoradiation endoscopic biopsies and imaging studies available for review. Patients who underwent planned surgery or salvage surgery (SS) within 6 months from BMT were excluded. We reviewed the pattern of relapse over time. Local-regional disease (LRD) after BMT was classified as regional disease (RD) or luminal-only disease (LD). Overall survival (OS) probabilities were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: For 276 patients, the median follow-up time was 53.0 months (95% confidence interval [CI], 47.3-58.7). A total of 184 (66.7%) patients had a persistent disease or relapse after BMT: 120 distant metastases (43.5% of 276) and 64 LRD (23.2% of 276). Of 64 LRD, 58 (91%) were diagnosed within 2 years of BMT and 63 (98%) were diagnosed within 3 years (see Table). Twenty-three of 64 LRD patients underwent SS. For patients with SS, the median OS time from diagnosis of LRD was 58.0 months (95% CI, not reached), and that for patients without SS was 9.0 months (95% CI, 7.3-10.7); this difference was highly significant (p < 0.001). Conclusions: Our data suggest that 91% of LRD occurred within 2 years after BMT and the OS with SS for LRD was better than that without SS. These data can contribute to the development of an evidence-based surveillance strategy. [Table: see text]

Adjuvant chemoradiotherapy in patients (pts) with resectable gastric (GC) or gastroesophageal junction cancer (GEJC): A monoinstitutional experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14711-e14711
Author(s):  
Barbara Soini ◽  
Giuseppe Pani ◽  
Orazio Caffo ◽  
Michela Frisinghelli ◽  
Antonello Veccia ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Adjuvant Chemoradiotherapy ◽  
Consecutive Series ◽  
Gastroesophageal Junction Cancer ◽  
Chemotherapy Side Effects ◽  
Grade 3

e14711 Background: Several studies have investigated the role of adjuvant chemotherapy ± radiotherapy showing conflicting results. In this retrospective study we report our monoinstitutional experience in pts with resectable GC or GEJC, treated with adjuvant chemoradiotherapy. Methods: Between January 2004 and August 2010 a consecutive series of 48 pts (34 male and 14 female) with a median age of 61 years (range 45-76) underwent a curative resection for GC or GEJC. All pts were treated with adjuvant chemoradiotherapy according to Mc Donald protocol (NEJM 2001;345:725-30). Thirty-three tumors (69%) were localized at the antrum or corpus level and 9 (19%) at the cardias. Thirty-one patients (64 %) had a T3-T4 tumor and 46 (95%) had nodal metastases.Treatment consisted of fluorouracil (5FU) 425 mg/m2 per day plus leucovorin (L) 20 mg/m2 per day, for 5 days, followed by radiotherapy 4500 cGy at 180 cGy per day, given 5 days per week for 5 weeks, with 5FU (400 mg/m2 per day) and L (20 mg/m2 per day) during the first four and the last three days of radiotherapy. One month after the completion of RT, two five-day cycles of 5FU (425 mg/m2 per day) plus L (20 mg/m2 per day) were given one month apart. Results: The treatment was completed in all but 4 pts: 2 pts stopped treatment due to chemotherapy side effects, 1 pt died due to intestinal perforation, and 1 pt declined radiotherapy. Major toxicities consisted of: grade 3/4 neutropenia in 6 pts (12%) and grade 3/4 gastrointestinal toxicity in 8 pts (16 %). At a median follow-up of 25.5 months (range 7 - 68), the median disease free-survival (DFS) was 41 months (2-y DFS 59%, 3-y DFS 53%) and the median overall survival (OS) was 57 months (2-y OS 77%, 3-y OS 68%). Conclusions: Concomitant chemo-radiotherapy appears in our experience a feasible adjuvant regimen in curatively resected node positive gastric cancer. Despite the short follow-up, local control and survival rates seem promising and comparable to those reported in the literature.

Adjuvant nivolumab (NIVO) in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): Expanded efficacy and safety analyses from CheckMate 577.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4003-4003
Author(s):  
Ronan Joseph Kelly ◽  
Jaffer A. Ajani ◽  
Jaroslaw Kuzdzal ◽  
Thomas Zander ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Distant Recurrence ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer

4003 Background: In CheckMate 577 (NCT02743494), NIVO demonstrated a significant and clinically meaningful improvement in disease-free survival (DFS; primary endpoint) vs placebo (PBO) and was well tolerated in patients (pts) with resected (R0) stage II/III EC/GEJC who received neoadjuvant CRT and had residual pathologic disease. Median DFS doubled with NIVO vs PBO (22.4 vs 11.0 months; HR 0.69; 96.4% CI 0.56–0.86; P = 0.0003). Serious treatment-related adverse events (TRAEs) and TRAEs leading to discontinuation were reported for < 10% of pts with NIVO and 3% with PBO. Methods: Pts were randomized 2:1 to NIVO 240 mg or PBO Q2W for 16 weeks, followed by NIVO 480 mg or PBO Q4W. Here, we present additional efficacy, safety, and quality-of-life (QoL) data from CheckMate 577. Results: 794 pts were randomized (NIVO, 532; PBO, 262). Distant recurrence was reported for 29% vs 39% and locoregional recurrence for 12% vs 17% of pts in the NIVO vs PBO groups, respectively. Median distant metastasis-free survival was 28.3 vs 17.6 months with NIVO vs PBO (HR 0.74; 95% CI 0.60–0.92). Median progression-free survival 2 (PFS2; time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death, whichever is earlier) was not reached with NIVO vs 32.1 months with PBO (HR 0.77; 95% CI 0.60–0.99). TRAEs with potential immunologic etiology (select TRAEs; sTRAEs) reported for NIVO are presented in the table. Results for the FACT-ECS and FACT-G7 showed similar trends for QoL improvement from baseline for NIVO and PBO during treatment and maintained benefit post-treatment. Conclusions: Adjuvant NIVO demonstrated clinically meaningful efficacy, an acceptable safety profile, and maintained QoL, providing further support for its use as a new standard of care for pts with resected EC/GEJC who received neoadjuvant CRT with residual pathologic disease. Clinical trial information: NCT02743494. [Table: see text]

RA03.06: IMPROVED SURVIVAL AFTER ESOPHAGECTOMY FOR ESOPHAGEAL OR GASTROESOPHAGEAL CANCER IN THE LAST 25 YEARS

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 24-24
Author(s):  
Annelijn Slaman ◽  
Giovanni Pirozollo ◽  
Wietse Eshuis ◽  
Suzanne Gisbertz ◽  
Mark I Van Berge Henegouwen
Keyword(s):  
Conflicts Of Interest ◽  
Minimally Invasive Esophagectomy ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Rank Tests ◽  
Tertiary Referral Center ◽  
Invasive Esophagectomy ◽  
Kaplan Meier ◽  
Esophagectomy For Cancer

Abstract Background Many things have changed in treatment for patients who underwent esophagectomy for cancer in the last decades, such as neoadjuvant chemoradiotherapy and minimally invasive esophagectomy. This study was performed to evaluate developments in survival after esophagectomy for cancer over the last 25 years. Methods Patients who underwent esophagectomy for esophageal or gastroesophageal junction (GEJ) carcinoma between January 1993 and February 2017 were selected from a prospectively maintained database of a tertiary referral center, guaranteeing minimum follow-up of 12 months at time of the analyses. Patients were divided in different groups according to year of esophagectomy: A) 1993–1997, B) 1998–2002, C) 2003–2007, D) 2008–2012, and E) 2013–2017. Follow-up was truncated at a maximum of 60 months. Survival outcomes were assessed by Kaplan Meier estimate, using log-rank tests to compare survival curves between groups. Results A total of 1503 patients were included. Median follow-up was 55.8 months (IQR 31.5–60.0). Median estimated overall survival for all patients was 36.4 months (95% CI 31.8–40.9) and improved from 26.1 months (95% CI 19.3–32.8, period A) to 46.1 months (95% CI 36.9–55.3) in period E (P = 0.001). Cumulative 1- and 3-years survival increased from 69.3% and 42.4% (period A) to 79.2% and 54.6% (period E, P < 0.05) respectively. The cumulative 5-years survival improved from 30.5% (period A) to 43.4% in period D (P = 0.007). Conclusion Survival after esophagectomy for cancer improved significantly in the last 25 years. Additional investigations should be performed to assess predictive factors for survival, in order to further improve survival. Disclosure All authors have declared no conflicts of interest.

scholarly journals Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 400 ◽  
Author(s):  
Seiichiro Mitani ◽  
Hisato Kawakami
Keyword(s):  
Gastroesophageal Junction ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Drug Conjugates ◽  
Gastroesophageal Junction Cancer ◽  
Development Of Resistance ◽  
Epidermal Growth ◽  
Antibody Drug

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies.

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