Advanced oesophago-gastric adenocarcinoma in older patients in the era of immunotherapy. A review of the literature

Abstract

Gastric (G) and gastro-esophageal junction (GEJ) adenocarcinomas are of the most common and deadly cancers worldwide and affect mainly patients over 70 years at diagnosis. Older age has been associated in gastric cancers with distal tumour location, well-differentiated adenocarcinoma and microsatellite instability and is not identified itself as an independent prognostic factor. As immune checkpoint inhibitors recently changed the landmark of advanced G and GEJ adenocarcinomas treatment, we decided to perform a literature review to define the evidence-level of clinical data in older patients. This work underlined the lasting low -inclusion rate of older patients and -implementation rate of frailty screening tools in clinical trials in G/GEJ carcinomas. In the first-line metastatic setting, two prospective randomized phase III studies have specifically assessed the efficacy of chemotherapy in older patients with HER2-negative gastric cancers, demonstrating the feasibility of reduced dose oxaliplatin-based chemotherapy regimen in this population. Only few data are available in HER2-positive tumors, or in the second-line setting. Furthermore, no specific trial with immune checkpoint inhibitors was performed in older frail patients whereas their benefit/adverse events ratio make them attractive candidates in this patient's population. We conclude that older fit patients can be treated in the same way as younger ones and included in clinical trials. Improving the outcome of older frail patients should be the oncology community next focus by implementing targeted interventions before initiating cancer therapy and designing specific clinical trials. Frailty screening tools and geriatric data collection have to be implemented in routine-practice and clinical trials.

Antimicrobial Step-Down Therapy versus Conventional Antimicrobial Therapy in the Treatment of Patients with Sepsis

“…In the present study, the results showed that antimicrobial step-down therapy was associated with a significantly higher efficacy (85.29%) versus conventional antimicrobial therapy (61.29%), which was consistent with previous research results [ 18 , 19 ]. The efficacy of the convention antimicrobial therapy was lower than the results of prior research [ 20 ], which may be attributed to the limited number of study participants.…”

Phase II Clinical Trial to Study the Safety and Efficacy of Combined S-1 + Oxaliplatin Therapy as Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer in Older Patients

“…On the other hand, a randomized phase III trial was conducted in Korea comparing capecitabine monotherapy with CapeOX as standard therapy for rst-line treatment of metastatic GC patients over 70 years old. In the rst interim analysis, the median OS was better with CapeOX (11.1 months) than with single-agent capecitabine (6.3 months), although with no signi cant difference, and the independent data monitoring committee recommended discontinuation of the trial [32]. This trial was conducted in older patients with PS 0-2 and preserved organ function, suggesting that standard treatment is feasible and effective in this population.…”

Efficacy and adverse events of immune checkpoint inhibitors in esophageal cancer patients: Challenges and perspectives for immunotherapy

“…[4][5][6] Fluoropyrimidine plus platinumbased chemotherapy has been widely used as first-line treatment for patients with advanced EC. 5,6 These systemic therapies rely primarily on cytotoxic chemotherapy, and the outcomes remain poor; however, emerging immunotherapy therapies (represented by cytotoxic T lymphocyte-associated antigen-4 [CTLA-4], programmed cell death protein 1 [PD-1], and programmed death ligand 1 [PD-L1] antibody drugs) have greatly improved treatment efficacies. [7][8][9][10][11] Immune checkpoint (IC) molecules are biological macromolecules expressed on human immune cells or other somatic cells that can regulate the immune response.…”

“…EC patients in the early stage, often choose surgery; however, treatment options for metastatic EC are limited. First‐line chemotherapy treatment for metastatic patients is mainly based on fluorouracil or paclitaxel combined with platinum 4–6 . Fluoropyrimidine plus platinum‐based chemotherapy has been widely used as first‐line treatment for patients with advanced EC 5,6 .…”