title: Surrogate end-points for overall survival in 22 neoadjuvant trials of gastro-oesophageal cancers.
abstract: The surrogacy between disease-free survival (DFS) and overall survival (OS) has been evaluated in patients with gastric cancer who received adjuvant chemotherapy. Similar analyses in patients who have undergone neoadjuvant chemoradiotherapy (CTRT) or chemotherapy (CT) for gastro-oesophageal (GE) cancer have not yet been performed.
  
  
  
  We evaluated the correlation between DFS and pathologic complete response (pCR) with OS in patients with GE carcinomas enrolled in randomised studies. A weighted linear regression analysis was used to evaluate surrogacy. Correlations were evaluated by squared correlation R2. Surrogacy of DFS and pCR with OS was assessed through the correlation between end-points and OS (individual-level surrogacy), and between the treatment effects on the end-points (trial-level surrogacy). Correlations were weighted by the number of patients in the intent-to-treat population.
  
  
  
  Twenty-two trials were included for a total of 4749 patients that received CTRT or CT for gastric or oesophageal cancers. Treatment effect on surrogates did not correlate with treatment effect on OS (R2= 0.27, and R2= 0.17, for DFS and pCR) at the trial level. In subgroup analysis surrogacy of DFS did not vary according to histology or treatment modality but was good in gastric cancer and poor in oesophageal cancers.
  
  
  
  DFS and pCR did not correlate with OS, and should not be used as surrogate end-points in patients with GE cancer who have undergone neoadjuvant therapy. OS should still represent the primary end-point to compare treatments in future randomised clinical trials.
authors.affiliation: Oncology Unit, Oncology Department, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio (BG), Italy. Electronic address: faupe@libero.it.
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
authors.affiliation: Oncology Unit, Oncology Department, ASST Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tomasello
authors.affiliation: Oncology Unit, Oncology Department, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio (BG), Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D016014:Linear Models; D020360:Neoadjuvant Therapy; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers
keywords: Gastric cancer; Neoadjuvant therapy; Oesophageal cancer; Overall survival; Surrogate end-points