scholarly journals Trifluridine/tipiracil in patients with metastatic gastroesophageal junction cancer: a subgroup analysis from the phase 3 TAGS study

2021 ◽  
Author(s):  
Wasat Mansoor ◽  
Hendrik-Tobias Arkenau ◽  
Maria Alsina ◽  
Kohei Shitara ◽  
Peter Thuss-Patience ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Gastroesophageal Junction ◽  
Best Supportive Care ◽  
Tumor Type ◽  
Phase 3 ◽  
Gastroesophageal Junction Cancer ◽  
Disease Site ◽  
Previously Treated ◽  
Grade 3 ◽  
Primary Tumor Type

Abstract Background Patients with advanced gastroesophageal junction cancer (GEJC) have poor survival outcomes, and GEJC-specific data from trials evaluating agents in gastric cancers (GCs) as a whole are lacking. Trifluridine/tipiracil (FTD/TPI) was approved for previously treated metastatic GC or GEJC (mGC/mGEJC) based on results of the phase 3 TAGS trial. Subgroup analyses by primary tumor type (GC or GEJC) in TAGS are reported here. Methods Pa tients with mGC/mGEJC treated with  ≥ 2 prior chemotherapy regimens were randomized (2:1) to receive FTD/TPI or placebo, plus best supportive care. A pre-planned sub-analysis was performed to evaluate efficacy and safety outcomes by primary tumor type (GEJC or GC). Results Of 507 randomized patients, 145 (29%) had GEJC and 360 (71%) had GC as the primary disease site. Baseline characteristics were generally similar between the GEJC and GC subgroups, except that more patients in the GEJC subgroup had received  ≥ 3 prior regimens (72 vs. 59% in the GC subgroup). Survival benefit with FTD/TPI was observed in both subgroups. The overall survival hazard ratio for FTD/TPI vs placebo was 0.75 (95% CI 0.50–1.11) and 0.67 (95% CI 0.52–0.87) in the GEJC and GC subgroups, respectively. Grade ≥ 3 adverse events of any cause were reported in 75 (77%) and 192 (81%) FTD/TPI-treated patients in the GEJC and GC subgroups, respectively. No new safety concerns were noted with FTD/TPI. Conclusion As in patients with GC, FTD/TPI showed an efficacy benefit in patients with GEJC in the TAGS trial, along with demonstrating a manageable safety profile.

scholarly journals Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a randomized phase 3 study (TAGS)

2022 ◽  
Author(s):  
Kohei Shitara ◽  
Toshihiko Doi ◽  
Hisashi Hosaka ◽  
Peter Thuss-Patience ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Gastroesophageal Junction Cancer ◽  
Safety Outcomes ◽  
Previously Treated Patients ◽  
Grade 3

Abstract Background Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age. Methods In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m2 or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years. Results Among 507 randomized patients (n = 337 FTD/TPI; n = 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51–0.89), 0.73 (95% CI 0.52–1.02), and 0.67 (95% CI 0.33–1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients [40% (≥ 65 and ≥ 75 years); 29% (< 65 years)]; AE-related discontinuation rates did not increase with age [14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years)]. Conclusions The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.

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.

Trifluridine/tipiracil (FTD/TPI) in patients (pts) aged ≥65 years with metastatic gastric/gastroesophageal junction cancer (mGC/mGEJC): Subgroup analysis from TAGS.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4037-4037 ◽  
Author(s):  
Kohei Shitara ◽  
Toshihiko Doi ◽  
Hisashi Hosaka ◽  
Peter C. Thuss-Patience ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Gastroesophageal Junction ◽  
The Elderly ◽  
Best Supportive Care ◽  
Moderate Renal Impairment ◽  
Treatment Groups ◽  
Gastroesophageal Junction Cancer ◽  
Previously Treated ◽  
Dose Modifications ◽  
Ecog Ps

4037 Background: 60% of newly diagnosed GC pts are > 65 y of age, a proportion that is increasing. The global phase 3 study TAGS (NCT02500043) demonstrated the efficacy and safety of FTD/TPI in previously treated pts with mGC/mGEJC. Here we report results in the pt subgroup aged ≥65 in TAGS. Methods: Pts with mGC/mGEJC treated with ≥2 prior chemotherapy regimens were randomized (2:1) to receive FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. A preplanned efficacy/safety analysis was performed in pts aged ≥65 y. Results: Of 507 randomized pts, 228 (45%) were aged ≥65 y (range 65–89). The pt subset aged ≥65 y was similar to the overall population, except for a higher incidence of moderate renal impairment in the elderly subgroup (31% vs 17%). For pts aged ≥65 y, baseline characteristics were generally balanced across the treatment groups, although more pts treated with FTD/TPI than with placebo had ECOG PS 1 (69% vs 59%). FTD/TPI had an efficacy benefit in pts aged ≥65 y, and the FTD/TPI safety profile was similar in this subgroup vs the overall population (table). Treatment-related deaths (one in each treatment group) did not occur in pts aged ≥65 y. No drug-related deaths associated with cardiotoxicity were reported in pts aged ≥65 y. Although dose modifications were used more often in this subgroup, there was no increase in discontinuations vs the overall population. Conclusions: FTD/TPI was safe and effective in pts aged ≥65 y, who had a higher incidence of moderate renal impairment vs the overall population. Clinical trial information: NCT02500043. [Table: see text]

Trifluridine/tipiracil (FTD/TPI) in patients (pts) with metastatic gastroesophageal junction cancer (mGEJC): Subgroup analysis from TAGS.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4038-4038 ◽  
Author(s):  
Wasat Mansoor ◽  
Hendrik-Tobias Arkenau ◽  
MARIA ALSINA ◽  
Kohei Shitara ◽  
Mohamedtaki Abdulaziz Tejani ◽  
...  
Keyword(s):  
Placebo Group ◽  
Safety Profile ◽  
Early Stage ◽  
Gastroesophageal Junction ◽  
Metastatic Gastric Cancer ◽  
Best Supportive Care ◽  
Efficacy And Safety ◽  
Early Stage Disease ◽  
Gastroesophageal Junction Cancer ◽  
Disease Site

4038 Background: The incidence of GEJC is increasing in North America and Europe, especially among white men. Many pts present with metastatic disease or relapse locally or systemically after resection of early-stage disease. The global phase 3 study TAGS (NCT02500043) demonstrated the efficacy and safety of FTD/TPI in previously treated pts with metastatic gastric cancer (mGC)/mGEJC. Here we report results in the mGEJC subgroup from TAGS. Methods: Pts with mGC/mGEJC treated with ≥2 prior chemotherapy regimens were randomized (2:1) to receive FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. A preplanned efficacy and safety analysis was performed in pts with mGEJC. Results: Of 507 randomized pts, 145 (29%) had GEJC as the sole primary disease site (FTD/TPI, 98/337; placebo, 47/170). Of pts with mGEJC, 85% were male and 83% were white (overall population, 73% and 70%). Baseline characteristics were generally balanced for pts with mGEJC across treatment groups, except for fewer pts having prior gastrectomy (40% vs 55%) and more pts having received ≥3 prior regimens (74% vs 66%) in the FTD/TPI group than in the placebo group. FTD/TPI had an efficacy benefit in pts with mGEJC, and the FTD/TPI safety profile was similar in this subgroup and the overall population (table). Conclusions: FTD/TPI showed a manageable safety profile and efficacy benefit in pts with mGEJC in the TAGS trial, despite heavier pretreatment of the FTD/TPI than the placebo group. Clinical trial information: NCT02500043. [Table: see text]

scholarly journals Prognostic factors and a new scoring system for survival of patients irradiated for bone metastases

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dirk Rades ◽  
Rapha Haus ◽  
Steven E. Schild ◽  
Stefan Janssen
Keyword(s):  
Multivariate Analysis ◽  
Bone Metastases ◽  
Primary Tumor ◽  
Scoring System ◽  
Survival Rates ◽  
Karnofsky Performance Score ◽  
Tumor Type ◽  
Factor Scores ◽  
Survival Times ◽  
Primary Tumor Type

Abstract Background Personalized therapy for bone metastases should consider the patients’ remaining lifespan. Estimation of survival can be facilitated with scoring tools. A new tool was developed, specifically designed to estimate 12-month survival. Methods In 445 patients irradiated for bone metastases, radiotherapy regimen plus 13 factors (age, gender, Karnofsky performance score (KPS), primary tumor type, interval between cancer diagnosis and RT of bone metastases, visceral metastases, other (non-irradiated) bone metastases, sites of bone metastases, number of irradiated sites, pathological fracture, fractionation of RT, pre-RT surgery, pre-RT administration of bisphosphonates/denosumab, pre-RT systemic anticancer treatment) were retrospectively analyzed for survival. Factors achieving significance (p < 0.05) or borderline significance (p < 0.055) on multivariate analysis were used for the scoring system. Twelve-month survival rates were divided by 10 (factor scores); factor scores were summed for each patient (patient scores). Results On multivariate analysis, survival was significantly associated with KPS (hazard ratio (HR) 1.91, p < 0.001) and primary tumor type (HR 1.12, p < 0.001); age achieved borderline significance (HR 1.14, p = 0.054). These factors were used for the scoring tool. Patient scores ranged from 8 to 17 points. Three groups were designated: 8–9 (A), 10–14 (B) and 15–17 (C) points. Twelve-month survival rates were 9, 38 and 72% (p < 0.001); median survival times were 3, 8 and 24 months. Conclusions This new tool developed for patients irradiated for bone metastases at any site without spinal cord compression allows one to predict the survival of these patients and can aid physicians when assigning the treatment to individual patients.

scholarly journals KEYNOTE-061: pembrolizumab vs paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer

2018 ◽  
Vol 29 ◽  
pp. vii49
Author(s):  
Kohei Shitara ◽  
Kei Muro ◽  
Taroh Satoh ◽  
Takao Tamura ◽  
Keisho Chin ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Gastroesophageal Junction Cancer ◽  
Previously Treated

Bronchioloalveolar lung CTCs retain cytomorphologic features of primary tumor type

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 19118-19118 ◽  
Author(s):  
D. Marrinucci ◽  
K. Bethel ◽  
J. M. Fisher ◽  
D. Lazar ◽  
P. Kuhn ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Tumor Type ◽  
Primary Tumor Type

Efficacy and tolerability of bevacizumab (BEV) plus capecitabine and cisplatin (XP) in Chinese patients (pts) with locally advanced or metastatic gastric/gastroesophageal junction cancer (AGC): Results from the AVATAR study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 73-73 ◽  
Author(s):  
Lin Shen ◽  
Jin Li ◽  
Jian-Ming Xu ◽  
Hong-Ming Pan ◽  
Guanghai Dai ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Chinese Patients ◽  
Double Blind Study ◽  
Double Blind ◽  
Gastroesophageal Junction Cancer ◽  
The Difference ◽  
Grade 3

73 Background: In the AVAGAST study, chemotherapy (fluoropyrimidine and cisplatin) + BEV did not significantly improve overall survival (OS) vs. chemotherapy + placebo. Geographic differences in efficacy were observed, but only 12 Chinese pts were included. AVATAR, a study similar in design to AVAGAST, is a randomized double-blind study conducted exclusively in China in pts with AGC. Methods: Pts aged >18 years with gastric adenocarcinoma were randomized 1:1 to XP + BEV 7.5 mg/kg or placebo + XP. The primary objective was OS; secondary objectives included progression-free survival (PFS) and safety. Results: Baseline characteristics of the 202 pts were well balanced. The primary efficacy endpoint of improved OS in the BEV arm was not met (HR 1.11, 95% CI 0.79–1.56; p=0.5567; see table ). BEV + XP was well tolerated. Grade 3–5 adverse events (AEs) and serious AEs were 60% and 19% for BEV and 68% vs. 21% for placebo, respectively. Grade 3–5 AEs of special interest with BEV occurred in 8% of BEV pts and 15% of placebo pts; the difference was mainly due to grade 3–5 haemorrhage (BEV 4%, placebo 12%). Conclusions: Addition of BEV to XP in Chinese pts with AGC did not significantly improve outcomes in AVATAR. The results from AVATAR are consistent with the findings seen in the Asian sub-population of the previous AVAGAST study. [Table: see text]

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