The evolving immunotherapeutic landscape in advanced oesophagogastric cancer

Abstract

Improvements in median overall survival in the advanced oesophagogastric (OG) setting have plateaued, underlining the need for improved therapeutic approaches in this patient population. Immunotherapeutics are inducing unexpected durable responses in an expanding list of advanced disease indications. Although OG cancers have traditionally been considered to be more challenging to treat with immunotherapy than some other malignancies because of their variable tumour mutational burden and relative scarcity of infiltrating T cells, immune checkpoint inhibitor (ICPI) trials conducted over the last few years suggest there is an important role for these treatments. ICPI efficacy may be demonstrated in specific molecular subtypes of OG cancer. This review outlines the improvements in defining predictive biomarkers of responsiveness to ICPIs. Increasingly, identification of an expanding list of ICPI resistance mechanisms will drive biomarker-directed research. In addition, the specific rationale to combine ICPIs with chemotherapies, radiotherapies, targeted therapies and other novel immunotherapeutic drugs will be discussed.

Combination of Oxaliplatin and 5-Fluorouracil/Leucovorin for Advanced Esophageal Squamous Cell Carcinoma Refractory or Intolerant to Standard Therapies

“…However, it was reported that the RR was 10–30% and not all patients obtained an immunotherapy benefit [11, 12]. An attempt to identify those benefiting from immunotherapy using biomarkers has been made [13]. Thus, a significant unmet need for more effective treatments for metastatic esophageal cancer still exists.…”

Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217)

“…Although therapy with immune checkpoint inhibitors is promising, effects are limited to subgroups of patients and up to date no biomarkers are available to reliably select responding patients. The newly classified molecular subtypes may help to identify responders with subgroups like EBV or MSI to be more immunogenic [32,33]. In addition, resistance to HER2-targeting in HER2-positive tumors might be present upfront or will eventually develop during treatment, particularly by loss of HER2 amplification [34].…”

Timeliness of cancer care in a regional Victorian health service: A comparison of high‐volume (Lung) and low‐volume (oesophagogastric) tumour streams

“…However, treatment at larger treatment centres has been shown to culminate in better survival for both lung 18,19 and OG 20‐22 cancer patients. This evidence may suggest that the larger treatment centres have more streamlined care services than smaller centres, highlighting the benefits of service centralisation 4 . In regional areas, however, transport is a major barrier to accessing treatment.…”

“…The incidence of lung cancer is second only to prostate cancer in men and breast cancer in women, 3 making it a high‐volume tumour stream. Oesophagogastric (OG) cancer, on the other hand, is a low‐volume (less common) cancer 4 . In Australia, the 5‐year survival rate in the last 10 years has been shown to be 17.4% in lung cancer and 22.0% in OG cancer 5…”

“…Oesophagogastric (OG) cancer, on the other hand, is a low-volume (less common) cancer. 4 In Australia, the 5-year survival rate in the last 10 years has been shown to be 17.4% in lung cancer and 22.0% in OG cancer. 5 Most factors associated with early deaths due to cancer are pathological, such as stage at diagnosis and site of metastasis.…”