Biomarker-defined benefit from FLOT plus nivolumab in metastatic gastroesophageal cancer: Extended follow-up and immune-inflammatory markers of the phase II IKF-AIO-moonlight trial.
Abstract
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.