• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed—mutation rate of the marker higher than expected

Abstract

SummaryBackgroundIn operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies.MethodBiomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of a phase II pilot study.ResultsFrom 2007–2012, the • Pancho trial recruited 235 patients with operable esophageal cancer in Austria. A total of 181 patients were eligible and could be subjected to mark53 analysis and randomization. After randomizing 74 patients, the overall TP53 mutation rate was 79%. However, due to the high prevalence of marker positivity, the number of projected patients was increased to 181 patients in order to ensure a sufficient number of marker-negative patients. After completion of the trial, the overall TP53 mutation rate was 77.9%.ConclusionDue to high medical need, the recruitment for the academic trial was excellent. Mark53 analysis clearly detected more mutations in the TP53 gene as compared to the cancer-specific p53 literature. Final analysis examining the interaction between the mark53 status and the effect of chemotherapies applied in the • Pancho trial is now awaited.

Predicting Response to Neoadjuvant Therapy in Oesophageal Adenocarcinoma

“…A possible reason for this divergent result in Fareed et al may be due to the study’s homogeneous treatment of p53 [ 84 ]. Recent studies suggest that significant differences exist for NAT response between groups that have normal p53 compared to a mutated or absent p53 [ 60 , 61 , 69 ]. Therefore, future biomarker studies must be wary of mutant p53.…”

“…Furthermore, as 5FU and cisplatin act in a p53-dependent fashion [58,59], Kandioler explored the effect of mutant TP53 on NAT response and found significant difference in response between patients with normal and mutant TP53 [60]. Clinical validation of TP53 s status as a predictive biomarker is currently being explored in the multicentre Pancho trial (ClinicalTrials.gov, accessed on 7 December 2021, Identifier: NCT00525200) [61].…”

Minimally invasive esophagectomy

“…As a result, HMIE demonstrated to have less postoperative major morbidity, specifically significantly less pulmonary complications. Moreover, in a recent 3-year followup an overall survival of 67% (95% confidence inter- val [CI] 57-75) in the HMIE group versus 55% (95% CI [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] in the open-procedure group was demonstrated [44]. In the MIOMIE trial, an Austrian group compared open esophagectomy versus HMIE (with thoracotomy) as well.…”

“…In the MIOMIE trial, an Austrian group compared open esophagectomy versus HMIE (with thoracotomy) as well. They could show that morbidity, mortality, and oncological long-term outcome were equal to the classical open Ivor Lewis approach [45,46]. However, with enough expertise, both parts can be accomplished minimally invasively when a stepwise approach with proctoring from a high-volume reference center is available in order to steepen the learning curve.…”

TP53 is not a prognostic marker—clinical consequences of a generally disregarded fact

“…A standardized marker test (Mark53® test; Mark53 Ltd, Vienna, Austria), which has been previously assessed in phase II biomarker trials (Table ), is used and validated in that trial. The trial is completed and first results have been recently published …”