Chemo-immunotherapy in gastric cancer is more effective when administered in parallel

Although associated with lower toxicity, mFOLFOX plus nivolumab and ipilimumab administered in parallel was more effective in patients with gastric cancer than mFOLFOX induction followed by nivolumab plus ipilimumab, results from the Moonlight trial showed.

In patients with HER2-negative, metastatic, or locally advanced oesophagogastric adenocarcinoma, first-line treatment with mFOLFOX plus nivolumab has become the standard-of-care [1]. However, this regimen comes with substantial toxicity (59% grade ≥3). One part of the phase 2 Moonlight trial (NCT03647969) compared the efficacy and safety of mFOLFOX and nivolumab plus ipilimumab administered either in parallel or sequential. Prof.  Sylvie Lorenzen (Klinikum rechts der Isar, TU München, Germany) presented the results [2].

This part of the Moonlight trial enrolled 90 patients with previously untreated HER2-negative metastatic or locally advanced adenocarcinoma of the stomach or gastro-oesophageal junction. Participants were randomised 2:1 to parallel treatment with mFOLFOX, nivolumab and ipilimumab or 3 cycles of mFOLFOX induction followed by nivolumab plus ipilimumab (sequential arm). The primary endpoint was progression-free survival (PFS) at 6 months and the main secondary endpoints were overall survival, objective response rate (ORR), and safety.

After a median follow-up of 9.3 months, the median PFS was 7.29 months in the parallel arm versus 3.98 months in the sequential arm. PFS-rate at 6 months was 60% versus 30% (parallel vs sequential). In addition, parallel treatment favoured OS, ORR and median duration of response. Grade ≥3 treatment-related adverse events were more common in the parallel arm compared with the sequential arm (93% vs 73%).

“Although associated with higher toxicity, mFOLFOX chemotherapy plus nivolumab and ipilimumab administered in parallel was more effective compared with mFOLFOX induction followed by nivolumab plus ipilimumab. Therefore, these results do not support the concept of chemotherapy induction followed by immunotherapy, but should be interpreted with caution due to the small sample size and low PD-L1 expression rate in both arms (PD-L1 combined positive score [CPS] ≥1 in 41%; CPS_{parallel arm} 43%; CPS_{sequential arm} 40%)” closed Prof. Lorenzen.

1. Janjigian YY, et al. Lancet 2021;398(10294):27–40.
2. Lorenzen S, et al. FOLFOX plus nivolumab and ipilimumab versus FOLFOX induction followed by nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: Results from the randomized phase II Moonlight trial of the AIO. Abstract 1203O, ESMO Congress 2022, 09–13 September, Paris, France.

Copyright ©2022 Medicom Medical Publishers



Posted on 16 November 202221 May 2024