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]

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 The Efficacy of Ramucirumab in the Treatment of Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis of RCTs

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hongqiong Yang ◽  
Yaojun Zhou ◽  
Liangzhi Wang ◽  
Tianyi Gu ◽  
Mengjia Lv ◽  
...  
Keyword(s):  
Response Rate ◽  
Meta Analysis ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer ◽  
Line Chemotherapy

Five electronic databases were searched for eligible records. Outcomes were presented and analyzed according to the objective response rate (ORR), progression-free survival (PFS) rate, and overall survival (OS) rate. Five records involving 2,024 participants were included in the study. The pooled analysis of OS and PFS were longer with ramucirumab (RAM) therapy than without RAM for OS (odds ratio OR = 0.90 , 95% confidence interval CI = 0.82 – 1.00 , p = 0.05 ) and PFS ( OR = 0.74 , 95 % CI = 0.57 – 0.96 , p = 0.02 ). Moreover, compared with the current first-line chemotherapy, the OS ( OR = 0.93 , 95 % CI = 0.83 – 1.04 , p = 0.19 ) and PFS ( OR = 0.82 , 95 % CI = 0.64 – 1.06 , p = 0.13 ) results were not significantly higher with RAM. The ORRs of the patients in the RAM therapy groups were significantly higher than those in the groups without RAM ( OR = 1.40 , 95 % CI = 1.14 – 1.73 , p = 0.001 ).

scholarly journals Addition of Platinum Derivatives to Fluoropyrimidine-Based Neoadjuvant Chemoradiotherapy for Stage II/III Rectal Cancer: Systematic Review and Meta-Analysis

2019 ◽  
Vol 111 (9) ◽  
pp. 887-902 ◽  
Author(s):  
Felix J Hüttner ◽  
Pascal Probst ◽  
Eva Kalkum ◽  
Matthes Hackbusch ◽  
Katrin Jensen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Distant Recurrence ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

Abstract Background Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial. Methods PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided. Results Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities. Conclusions Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients.

Trastuzumab (TRA) in combination with different first-line chemotherapies for treatment of HER2-positive metastatic gastric or gastroesophageal junction cancer (MGC): Findings from the German noninterventional observational study HerMES.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4065-4065 ◽  
Author(s):  
Susanna Hegewisch-Becker ◽  
Enno Moorahrend ◽  
Hendrik Kröning ◽  
Volker Petersen ◽  
Carla Hannig ◽  
...  
Keyword(s):  
Observational Study ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Observation Time ◽  
Phase Iii ◽  
Her2 Positive ◽  
Gastroesophageal Junction Cancer ◽  
Few Data ◽  
Eortc Qlq

4065 Background: The international phase III study ToGA has recently shown that TRA is effective in prolonging survival in HER2-positive MGC. However, few data are available for TRA as part of routine clinical practice. Methods: This non-interventional observational study was conducted to evaluate the efficacy, safety and feasibility of TRA in previously untreated pts with HER2-positive MGC. Results: Between Apr 2010 and Jan 2012, data from 110 pts were collected. All pts were evaluable for safety. Baseline pt characteristics were as follows: median age 63 yrs (range 29–88); gender (male 70%; female 29%); ECOG PS (0: 25%; 1: 50%; 2: 15%; 3: 5%); distant mets (91%); liver mets (54%), lymph node mets (35%); peritoneal carcinomatosis (23%). The median duration of TRA treatment was 4.4 months (0–17.1). According to the schedule of chemotherapy TRA was administered every 2–3 wks in a median dose of 4–6 mg/kg BW. Only 28% of pts received TRA according to the label in combination with cisplatin and 5-FU or capecitabine. The remainder received: cisplatin, 5-FU and leucovorin (17%); 5-FU, leucovorin, oxaliplatin and docetaxel (8%); 5-FU, leucovorin and oxaliplatin (7%); capecitabine (6%); other combinations (25%); TRA monotherapy (7%). Although most pts didn’t receive cisplatin-based therapy, preliminary median progression-free survival was 6.8 months, thus comparable to the ToGA data. Most common adverse events (AEs, all grades) were diarrhoea (7%), vomiting (5%) and nausea (5%). Most common grade 3/4 AEs were vomiting (3%), nausea (2%) and fatigue (2%). Health-related quality of life as assessed by EORTC QLQ-C30 and QLQ-STO22 remained stable during observation time. An updated analysis of approx. 200 pts will be presented at the meeting. Conclusions: TRA combined with diverse chemotherapies is safe and effective in the routine treatment of MGC. Cisplatin-free less toxic regimens are feasible and equally effective. The results are in line with those from the ToGA trial and suggest that treatment with TRA should be regarded as standard of care for pts with HER2-positive MGC.

scholarly journals The addition of bevacizumab to fluoropyrimidine, irinotecan and oxaliplatin-based therapy improves survival for patients with metastatic colorectal cancer (CRC): Combined analysis of efficacy

2008 ◽  
Vol 55 (4) ◽  
pp. 11-16 ◽  
Author(s):  
I. Popov ◽  
M. Milicevic ◽  
Lj. Radosevic-Jelic
Keyword(s):  
Overall Survival ◽  
Median Duration ◽  
Statistical Power ◽  
Response Rate ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Group 5

Background: The primary objective of the analysis was to compare duration of survival in patients who received bevacizumab plus 5FU/LV, irinotecan or oxaliplatin based chemotherapy with the survival rate in a combined control groups of patients who received the same protocols alone, without bevacizumab. Methods: Pooling of the data from the several studies allows evaluation of efficacy end points with greater statistical power to detect real differences between the groups of patients who were and were not treated with bevacizumab. The 10 studies have to be used for analysis were well designed, prospective trials conducted in patients with metastatic colorectal adenocarcinoma. Results: The median duration of survival was 18/12/11 months median duration of progression free survival was 8.8/7/6.7 months and response rate was 34/14/12% in the 5-FU/LV/bevacizumab group, 5-FU/LV CI group, and bolus 5-FU/LV group, respectively. Difference in OS for patients who received bevacizumab with 5-FU/LV in comparison to 5-FU/LV alone is up to 7 months. The median duration of survival for bevacizumab plus irinotecan-based chemotherapy was 20 months, median duration of progression free survival was 11 months and response rate was 45%. Difference in OS, PFS and RR for patients who received bevacizumab plus irinotecan-based chemotherapy in comparison to irinotecan-based chemotherapy alone is up to 5 months, 4.5 months and 10%. For oxaliplatinbased protocols tumor response was 43-53%, overall survival was 16.4-19.4 months and the median progression free survival was 8-9 months. The median duration of survival was 26 months (benefit is up to 10 months), median duration of progression free survival was 19 months (benefit is up to 10 months) and response rate was 59% (benefit is up to 16%) were achieved for bevacizumab plus FOLFOX4 (oxaliplatin/ inf.5FU/LV). Conclusions: Addition of bevacizumab to 5-FU/LV, irinotecan or oxaliplatin-based chemotherapy provided significantly and clinically meaningful improvement in overall survival, disease-free survival and response rate compared with 5-FU/LV, irinotecan or oxaliplatin- based chemotherapy alone in patients with metastatic CRC.

scholarly journals Progression-Free Survival as Early Efficacy Endpoint in Resectable Esophageal Cancer Treated With Neoadjuvant Therapy: A Systematic Review

2022 ◽  
Vol 11 ◽  
Author(s):  
Jie Zhu ◽  
Jin Tao ◽  
Zhen Dai ◽  
Yan Tan ◽  
Li Jiang ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Neoadjuvant Therapy ◽  
Subgroup Analysis ◽  
Pearson Correlation ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Resectable Esophageal

To investigate literature-based evidence regarding progression-free survival (PFS) as an early efficacy endpoint in patients with resectable esophageal or gastroesophageal junction (GEJ) cancer receiving neoadjuvant therapy, this study identified large-scale randomized controlled trials (RCTs) with strict quality control. Twenty-four RCTs involving 7,514 patients were included. Trial-level correlation analysis was conducted to analyze the relationship between PFS hazard ratio (HR) and overall survival (OS) HR, Δ median PFS and Δ median OS. Correlation analysis at the neoadjuvant treatment arm level was performed between 1- to 5-year PFS and 5-year OS, median PFS and median OS. Subgroup analysis was performed in patients treated with standard neoadjuvant chemoradiotherapy (NCRT). The correlation was evaluated using the Pearson correlation coefficient r in weighted linear regression, with weight equal to patient size. In trial-level correlation, PFS were strongly associated with OS HR (r, 0.82 [95% confidence interval (CI), 0.42-0.97]) and Δ median survival (r, 0.83 [95% CI, 0.54-0.96]). In neoadjuvant treatment arms, there was a strong correlation between 1 to 5-year PFS rates and 5-year OS (r, 0.83-0.95), and median PFS and median OS (r, 0.97 [95% CI, 0.85-0.99]). NCRT subgroup analysis demonstrated acceptable consistency. In conclusion, we recommend PFS as an early efficacy endpoint in resected esophageal or GEJ cancer treated with neoadjuvant therapy.

scholarly journals Comparative Impact of PD-1 and PD-L1 Inhibitors on Advanced Esophageal or Gastric/Gastroesophageal Junction Cancer Treatment: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (16) ◽  
pp. 3612
Author(s):  
SuA Oh ◽  
Eunyoung Kim ◽  
Heeyoung Lee
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
L1 Use

Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have demonstrated varying effectiveness in treating esophageal or gastric/gastroesophageal junction (G/GEJ) cancer. Hence, this systematic review and meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 treatment in patients with esophageal or G/GEJ cancer by analyzing the types of medications. Randomized controlled trials comparing anti-PD-1/PD-L1 to control therapy were identified by searching PubMed, EMBASE, and ClinicalTrials.gov. The outcomes included overall survival (OS), progression-free survival (PFS) rates, and serious adverse events (SAEs), evaluating the differences in therapy types, including a comparison between PD-1 and PD-L1 inhibitors. Eight studies were included in the analysis. PD-1/PD-L1 inhibitors affected the overall OS rate increment without influencing the PFS rate (HR, 0.837; 95% CI, 0.753–0.929; p = 0.001; HR 0.991; 95% CI, 0.778–1.263; p = 0.942, respectively). Anti-PD-1 was significantly more beneficial for increasing OS and PFS than PD-L1 inhibitors. Anti-PD-1 and PD-L1 use was not significantly associated with SAE development in esophageal or G/GEJ cancer patients. PD-1/PD-L1 inhibitor use was associated with improved OS and PFS rate increase among PD-1 and PD-L1 inhibitors. Considering response variations to anti-PD-1/PD-L1 usage, more individualized treatments should be introduced in clinical practice.

scholarly journals Definitive radiotherapy for squamous cell carcinoma of the oral cavity: a single-institution experience

2021 ◽  
Vol 55 (4) ◽  
pp. 467-473
Author(s):  
Kristin Lang ◽  
Melissa Baur ◽  
Thomas Held ◽  
Rami El Shafie ◽  
Julius Moratin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Oral Cavity ◽  
Systemic Therapy ◽  
Single Agent ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Single Institution ◽  
Free Survival ◽  
Definitive Radiotherapy

Abstract Background Surgery is standard of care for oral cavity cancer (OCC). We provide a single-institution experience using definitive radiotherapy (RT) with or without concurrent systemic therapy for primary unresectable OCC. Patients and methods We retrospectively examined 49 patients with non-metastatic primary unresectable OCC treated with definitive RT between 2000 and 2019. The majority of patients (63.3%) were treated with definitive chemoradiotherapy while 26.5% were given single-agent cetuximab weekly simultaneous to definitive RT. Five patients were treated with definitive RT alone because of limited disease and no nodal involvement. Results Median follow-up was 73 months (range, 6–236 months), median progression free survival (PFS) was 42 months (range, 2–157 months), median local disease-free survival (LDFS) was 44 months (range, 2–157 months) and median overall survival (OS) from the time of RT initiation was 52 months (range, 5–236 months). There were 65.3% locoregional failures, 84.4% local and 15.6% distant metastasis. The majority of patients with local failure presented with American Joint Committee on Cancer (AJCC) Stage III–IV disease (59.2%). The 5-year Kaplan-Meier estimates for OS (III–IV vs. I–II) was 22.8% vs. 54.2 % (p = 0.03, HR 2.090, 1.1–4.2). Patients who were treated with systemic therapy had a significant better 5-year overall survival compared to those with RT alone (43.9% vs. 23.1%, p = 0.05, 1.0–4.1). RT with doses less than 70 Gy (p = 0.046, HR 2.1 (1.0–4.5) was associated with worse overall survival. Mucositis was the most common ≥ grade 3 acute toxicity and occurred in 19 patients (39%). Incidences of chronic toxicities were loss of taste, trismus, osteoradionecrosis and xerostomia. Conclusions Definitive RT with or without concurrent systemic agents in patients with unresectable OCC resulted in an eloquent rate of locoregional control and good overall survival rates and is currently the best available treatment option in this patient collective.

scholarly journals The Prognostic Significance of Combined Pretreatment Fibrinogen and Neutrophil-Lymphocyte Ratio in Various Cancers: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Rongqiang Liu ◽  
Shiyang Zheng ◽  
Qing Yuan ◽  
Peiwen Zhu ◽  
Biao Li ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Regression Analyses ◽  
Free Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Meta Regression

Purpose. The prognostic value of a new scoring system, termed F-NLR, that combines pretreatment fibrinogen level with neutrophil-lymphocyte ratio has been evaluated in various cancers. However, the results are controversial. The purpose of this study was to comprehensively analyze the prognostic value of F-NLR score in patients with cancers. Methods. An integrated search of relevant studies was conducted by screening the PubMed and Embase databases. Pooled hazard ratios, with 95% confidence intervals (CIs), for overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were calculated to estimate the prognostic significance of F-NLR score in patients with various tumors. A random effects model was used for comprehensive analysis, and subgroup and meta-regression analyses were used to explore sources of heterogeneity. Results. Thirteen articles reporting data from of 4747 patients were included in the study. Pooled analysis revealed that high F-NLR score was significantly associated with poor OS ( HR = 1.77 ; 95% CI, 1.51–2.08) and poor DFS/PFS ( HR = 1.63 ; 95% CI, 1.30–2.05). Subgroup and meta-regression analyses did not alter the prognostic role of F-NLR score in OS and DFS/PFS. Conclusions. Increased F-NLR score is significantly associated with poor prognosis in patients with cancers and can serve as an effective prognostic indicator.

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