LONGEVITY

Background and Rationale

Since pathologic complete response (pCR) is not yet an established surrogate endpoint (for an endpoint of event-free survival – EFS) in the setting of gastric or gastroesophageal junction (GEJ) cancer treated with neoadjuvant/perioperative chemotherapy, the objective of the analyses described here is to support understanding of whether and how a pCR treatment benefit may relate to the EFS. In fact, in a retrospective analysis of the MAGIC trial, pathological nodal staging outperformed pathological response in multivariable analyses, with pCR being no longer significant. However, this result is limited by the overall low frequency of major or complete pathological response to chemotherapy, especially older chemotherapy regimens, thus being underpowered to suggest a potential surrogacy. Real world data may be important to collect a high number of patients treated in the clinical practice and may offer the opportunity to reinforce the subsequent reassessment of the impact pCR in randomized clinical trials with more effective treatment strategies.

Study Design

LONGEVITY is an observational retrospective study enrolling patients with gastric (GC) or GEJ cancer treated with neoadjuvant/perioperative chemotherapy followed by radical surgery in the setting of the best clinical practice.

The study population includes patients 18 years of age or older with gastric or GEJ cancer cT ≥ 2, any cN, M0 or any cT, cN1-3, M0 (TNM classification 7th edition) with no distant metastases, treated with neoadjuvant chemotherapy followed by standard surgery as per standard practice and regardless the ability to subsequently receive postoperative chemotherapy according to the ESMO Guidelines.

The information about the clinical characteristics of patients, dates and regimen of neoadjuvant and adjuvant chemotherapy, date and type and outcome of surgery and survival/relapse status will be collected. Tissues from surgical procedure will be centrally collected and reviewed. Pathological response will be centrally assessed (according to Becker et al Classification (1a, pathological complete response, 1b, major pathological response with less than 10% viable cells in the tumor bed, 2, partial pathological response, with 10-49% viable cells in the tumor bed and 3, no response with 50% or more viable cells in the tumor bed). Additionally, nodal downstaging will be assessed if possible.

The association with EFS will be assessed. EFS is defined as the time from the date of neoadjuvant treatment start to disease recurrence, second primary tumor or death, whichever occurs first. EFS will be assessed, specifically median EFS and landmark EFS at 3 and 5 years if available.

A total of about 1000 patients from 5 Cancer Centers are planned to be included in the frame of the observational retrospective study.

Inclusion criteria

1. 18 years of age or older
2. Diagnosis of GC or GEJC
3. Clinical stage of cT ≥ 2, any cN, M0 or any cT, cN1-3, M0 (TNM classification 7th edition) with no distant metastases
4. Received neoadjuvant chemotherapy as per standard practice and regardless the ability to subsequently receive postoperative chemotherapy according to the ESMO Guidelines.

Exclusion criteria

1. Patients who did not receive pre-operative chemotherapy
2. Patients who did not undergo surgery for disease progression during pre-operative chemotherapy.
3. Patients with missing information regarding surgical outcomes and pathologic response.

The primary objectives are:

1. Assess pCR among patients with early stage gastric or GEJ cancer treated with a range of combination chemotherapies
2. Investigate the correlation between EFS and pCR in patients with perioperative early stage gastric or GEJ cancer.