Abstract 421P
Background
To date, there is no established role for maintenance therapy following 1L chemotherapy for GC. The a-MANTRA study aimed to evaluate the efficacy and safety of REGO as maintenance after 1L therapy in advanced GC/GEJ tumors.
Methods
This is a randomized, double-blind, placebo-controlled, multicenter phase II study in which HER2 neg GC/GEJ pts treated with platinum and fluoropyrimidines 1L therapy and disease control were randomized (1:1) to maintenance placebo (ARM A) or REGO (ARM B) starting at 80 mg up to 160 mg (once daily, d1-21, q28 days). The primary endpoint was median PFS1. Two-sided 80% CIs were planned for HR=0.57, one-sided α=0.10 (90% power), corresponding to 3-month increase in mPFS1. 118 subjects were needed to observe 88 events. The interim analysis (IA) was intended after 44 events.
Results
67 pts were randomized in 18 Italian Cancer Centers of which 64 (33 in ARM A, 31 in ARM B) received treatment. Most of pts were male (64.1%), Caucasian (96.8%), ECOG PS 0 (81.2%); median age was 66 (40-80) yrs. The main primary tumor side was proximal (64.1%) with intestinal subtype (54.7%), and peritoneum spread in 42.2%. IA revealed a 98% probability of achieving a significant result for mPFS1. The study was early halted due to introduction of anti-PD1 in 1L. The responses to 1L were PR (50.0%), CR (7.8%), and SD (42.2%). At a median 31-month (mth) follow-up (IQR 19.1-33-8), 28 (84.8%) and 26 (83.8%) events were reported. The main reason for discontinuation was PD (66.7% and 35.5%). mPFS1 was 3.91 (80% CI, 2.27-5.98) and 5.19 mth (80% CI, 4.0-7.26) [HR= 0.736 (80%CI, 0.51-1.04; p=0.1318)]. mOS was 11.25 and 16.97 mth (95%CI, HR=0.596 [0.318-1.103], p=0.1003). The most common G3-4 AEs for each arm were fatigue (3.0 vs 6.4%), thrombocytopenia (3.0 vs 3.2%), hand-foot syndrome (0 vs 12.9%).
Conclusions
Despite the favorable trend, since the sample was not sized for the statistical assumption, REGO as maintenance after 1L therapy did not reach statistically significant effects in mPFS1. No safety concerns were raised. Novel study proposals succeeding REGO with immunotherapy are needed.
Clinical trial identification
NCT03627728.
Legal entity responsible for the study
GOIRC.
Funding
Bayer.
Disclosure
A. Damato: Financial Interests, Institutional, Advisory Board: Daiichi Sankyo, Merck Serono. All other authors have declared no conflicts of interest.