Michael Masetti, Alexander Nieto, Sylvie Lorenzen, Thorsten Oliver Goetze, Peter C Thuss-Patience, Jorge Riera-Knorrenschild, Eray Goekkurt, Tobias Nicolaas Dechow, Thomas Jens Ettrich, Ralf Dieter Hofheinz, Kim Barbara Luley, Daniel Pink, Udo Lindig, Gunnar Folprecht, Gunter Schuch, Michael Bitzer, Volker Heinemann, Stefan Angermeier, Claus Bolling, Maria Loose, Sabine Junge, Claudia Pauligk, Salah-Eddin Al-Batran, Alexander Stein, Joseph Tintelnot
Low baseline MLR and positive CPS identified patients with particular benefit from FLOT + nivo that may outweigh the enhanced burden of intensified therapy.
BACKGROUND: First-line treatment of PD-L1-positive advanced gastroesophageal adenocarcinoma (GEA) combines doublet 5-FU/platinum with anti-PD1 inhibition. While triplet chemotherapy (FLOT/TFOX) has demonstrated efficacy alone, data on the combination of FLOT with immunotherapy remain sparse. Given the intensity of triplet immunochemotherapy in a palliative setting, selection of eligible patients for this combination is warranted.
METHODS: The AIO-STO-0417 trial enrolled 261 patients between November 2018 and February 2022 in five arms (A and A1 mFOLFOX+nivo/ipi; A2 mFOLFOX followed by nivo/ipi; B mFOLFOX or C FLOT+nivo). Extended follow-up and subgroup analysis were conducted for Arm C due to strong efficacy in the initial analysis. Subgroup analyses included PD-L1 (CPS), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). Prespecified quality-of-life analyses used changes in EORTC QLQ-C30 scores.
RESULTS: Median follow-up for Arm C was 12.7 months. Patients receiving FLOT + nivo (n = 52) had a mPFS of 7.0 months and mOS of 14.6 months. CPS≥ 1 was associated with numerically longer survival than CPS< 1 (PFS 7.6 vs 3.9 months; p = 0.13; mOS 17.4 vs 10.0 months; p = 0.15). Cox proportional hazard modeling showed an association of signet-ring cell histology, NLR and MLR with survival. Low NLR (mOS 25.5 vs 6.8 months; p = 0.088) and low MLR (mOS 28.4 vs 8.3 months p = 0.14) identified patients with numerically and clinically meaningful longer survival. Combination of CPS≥ 1 and low MLR defined patients with enhanced survival under FLOT + nivo (MLR: mOS 32.3 vs 7.4 months; p = 0.044). Considering quality of life, FLOT + nivo reduced pain but decreased physical functioning and increased fatigue.
CONCLUSIONS: Low baseline MLR and positive CPS identified patients with particular benefit from FLOT + nivo that may outweigh the enhanced burden of intensified therapy.
TRIAL REGISTRATION: NCT03647969.