Das Prodekanat für Forschung würdigt jeden Monat UKE Autorinnen und Autoren einer herausragenden Publikation, die in den vorangegangenen 2 Monaten hochrangig publiziert wurde. Ziel ist es, die am UKE enstandenen Forschungsergebnisse mit ihrer Bedeutung in der Wissenschaft einer größeren Öffentlichkeit am UKE vorzustellen. Der Aufruf zur Teilnahme richtet sich an Wissenschaftlerinnen und Wissenschaftler aller Fachgebiete. Einreichungsfrist für eine Bewerbung um die Auszeichnung des "Paper of the Month" ist jeweils Ende eines Monats (siehe Bewerbungsformular).
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UKE Paper of the Month October 2025
Perioperative pembrolizumab, trastuzumab and FLOT in HER2-positive localized esophagogastric adenocarcinoma: a phase 2 trial
Alexander Stein, Eray Goekkurt, Salah-Eddin Al-Batran, Nicolas Moosmann, Thomas Ettrich, Thorsten Goetze, Barbara Gruen, Nils Homann, Sylvie Lorenzen, Ralf-Dieter Hofheinz, Viktor Rempel, Gabriele Siegler, Christian Müller, Benjamin Thiele, Tobias Broering, Mariana Santos Cruz, Claudia Pauligk, Mascha Binder, Joseph Tintelnot
ABSTRACT:
Perioperative treatment strategies for HER2-positive esophagogastric adenocarcinoma remain suboptimal. Here in the open-label, phase 2 IKF/AIO PHERFLOT trial, we evaluated the safety and efficacy of adding pembrolizumab and trastuzumab to FLOT chemotherapy in patients with localized HER2-positive esophagogastric adenocarcinoma. The primary endpoints are the pathological complete response rate and the 2-year disease-free survival rate. Secondary endpoints include the R0 resection rate, feasibility and safety. Exploratory endpoints include clinical efficacy in molecularly defined subgroups. In this prespecified interim analysis, given the limited median follow-up period of 14.8 months, only one of the primary endpoints, the pathological complete response rate, and selected secondary endpoints, including the R0 resection rate, feasibility and safety, are reported here. Among 31 enrolled patients, 30 proceeded to R0 resection, and one patient declined surgery without disease progression. The combination regimen resulted in grade ≥3 treatment-related serious adverse events in 48.4% of patients (15 out of 31) aligning with established toxicity profiles of the respective agents and no treatment-related deaths. After four cycles of therapy, the pathological complete response rate was 48.4% (95% confidence interval 30.2–66.9; 15 out of 31) in the intention-to-treat population, and the subtotal regression rate (TRG1b according to Becker classification) was 19.4% (95% confidence interval 7.5–37.5; 6 out of 31), resulting in a major pathological response rate of 67.7% (95% confidence interval 48.6–83.3; 21 out of 31). Responses tended to be enriched in tumors with strong HER2 expression (immunohistochemistry 3+), high PD-L1 combined positive scores and lower T stage, but were also observed in substantial fractions of HER2 immunohistochemistry 2+/ISH+, T3 or T4 and combined positive scores <10 tumors. These findings support the feasibility and antitumor activity of perioperative chemoimmunotherapy targeting HER2 and PD-1 and warrant further validation in randomized trials. ClinicalTrials.gov registration: NCT05504720.
STATEMENT:
This study is the first to combine immune checkpoint inhibition, HER2-targeted therapy, and FLOT chemotherapy in the perioperative treatment of HER2-positive esophagogastric adenocarcinoma. We demonstrate that this approach is feasible and appears more effective than the current standard of care in terms of complete pathological response. Although disease-free survival data are not yet mature, the present findings indicate that this regimen warrants evaluation in a randomized trial against the current standard therapy for HER2-positive EGA. Moreover, with approximately half of the patients achieving a pathological complete response at the time of surgery, these results support the exploration of future surgery-free treatment strategies based on this combination.
Congratulations to all authors!
Next PoM: To apply, the publication must have been published in November 2025. Applications will be considered in two rounds of the selection process, i.e. two months. Please send your completed PoM application to Dr. Anne Wulf by 30/11/2025.