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)

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.

Anastomotic Leaks following Esophagectomy for Esophageal and Gastroesophageal Junction Cancer: The Key Is the Multidisciplinary Management

<b><i>Introduction:</i></b> Anastomotic leakage after esophagectomy is associated with high mortality and impaired quality of life. <b><i>Aim:</i></b> The objective of this work was to determine the effectiveness of management of esophageal anastomotic leakage (EAL) after esophagectomy for esophageal and gastroesophageal junction (GEJ) cancer. <b><i>Methods:</i></b> Patients submitted to esophagectomy for esophageal and GEJ cancer at a tertiary oncology hospital between 2014 and 2019 (<i>n</i> = 119) were retrospectively reviewed and EAL risk factors and its management outcomes determined. <b><i>Results:</i></b> Older age and nodal disease were identified as independent risk factors for anastomotic leak (adjusted OR 1.06, 95% CI 1.00–1.13, and adjusted OR 4.89, 95% CI 1.09–21.8). Patients with EAL spent more days in the intensive care unit (ICU; median 14 vs. 4 days) and had higher 30-day mortality (15 vs. 2%) and higher in-hospital mortality (35 vs. 4%). The first treatment option was surgical in 13 patients, endoscopic in 10, and conservative in 3. No significant differences were noticeable between these patients, but sepsis and large leakages were tendentially managed by surgery. At follow-up, 3 patients in the surgery group (23%) and 9 in the endoscopic group (90%) were discharged under an oral diet (<i>p</i> = 0.001). The in-hospital mortality rate was 38% in the surgical group, 33% in the conservative group, and 10% in endoscopic group (<i>p</i> = 0.132). In patients with EAL, the presence of septic shock at leak diagnosis was the only predictor of mortality (<i>p</i> = 0.004). ICU length-of-stay was non-significantly lower in the endoscopic therapy group (median 4 days, vs. 16 days in the surgical group, <i>p</i> = 0.212). <b><i>Conclusion:</i></b> Risk factors for EAL may help change pre-procedural optimization. The results of this study suggest including an endoscopic approach for EAL.

Benefits of an immunogenic personalized neoantigen nanovaccine in patients with high-risk gastric/gastroesophageal junction cancer

Personalized neoantigen vaccines have shown strong immunogenicity in clinical trial, but still face various challenges in facilitating an efficient antitumour immune response. Here we prepared a personalized neoantigen nanovaccine (PNVAC) platform for adjuvant cancer immunotherapy. PNVAC triggered superior protective efficacy against tumor recurrence and promoted longer survival than free neoantigens, especially when combined with anti-PD-1 treatment in a murine tumor model. A phase I clinical trial (ChiCTR1800017319) was initiated to study the safety, immunogenicity, and prophylactic effect of PNVAC on preventing tumor recurrence in patients with high-risk gastric/gastroesophageal junction cancer after adjuvant chemotherapy post-surgical resection. The 1- and 2-year disease-free survival rates were significantly higher than historical control. PNVAC induced both CD4+ and CD8+ T cell responses as well as antigen-experienced memory T cell phenotype. Furthermore, the immune response was persistent and remained evident one year after the vaccination. Our work provides a safe and feasible strategy for development of neoantigen vaccines to delay gastric cancer recurrence after surgery.

Health-related quality of life (HRQOL) in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC): Results of nivolumab plus chemotherapy (NIVO+chemo) versus chemo from CheckMate 649.

167 Background: CheckMate 649 (NCT02872116) is a randomized, open label phase 3 study in first line (1L) treatment of pts with advanced GC/GEJC/EAC. Primary analysis results showed statistically significant improvement in overall survival (OS) for NIVO+chemo vs. chemo in all randomized pts. We present HRQOL results for these pts, included as an exploratory study objective. Methods: HRQOL was assessed using EQ-5D-3L (EQ-5D) and Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga). Assessments were performed at baseline (BL), every 6 weeks during treatment and during follow-up. Change from BL EQ-5D Visual Analog Scale (VAS), Utility Index (UI) and FACT-Ga scores were analyzed using mixed models. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated with Kaplan-Meier estimators and stratified Cox models; deterioration/improvement was based on prespecified meaningful change thresholds. Results: 1581 pts were randomized to NIVO+chemo (n = 789) or chemo (n = 792). Among 1359 pts with BL and post-BL patient-reported outcomes (NIVO+chemo, n = 693; chemo, n = 666), BL scores for FACT-Ga total were similar between treatment groups. Least squares mean differences from BL favored NIVO+chemo at most visits for EQ-5D, FACT-Ga total, and Gastric Cancer Subscale (GaCS), and were comparable for other subscales (not shown). TTI generally favored NIVO+chemo (most HR > 1) but was not significantly different between arms. TTSD was longer in NIVO+chemo arm compared with chemo alone (all HRs < 1), except for Emotional Well-Being (WB); only GaCS and FACT-Ga total were significantly different between arms. TuDD showed statistically significant delays in deterioration (HR with CI < 1) for all scores expect Social WB. Conclusions: Compared with chemo alone, the addition of NIVO to chemo maintained HRQoL with a decreased risk of symptom deterioration in patients with previously untreated advanced or metastatic GC/GEJC/EAC. Together with improved OS, these data support NIVO+chemo as a new 1L standard treatment for GC/GEJC/EAC. Clinical trial information: NCT02872116. [Table: see text]