KEY TAKEAWAYS
- The MATTERHORN study phase 3 trial aimed to investigate the efficacy of perioperative durvalumab with FLOT in resectable GC/GEJC.
- Researchers noticed a statistically significant improvement in pCR for resectable GC/GEJC with the addition of durvalumab.
The global, phase 3, randomized, double-blind, placebo (P) -controlled MATTERHORN study (NCT04592913) investigates perioperative durvalumab (D) with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in gastric cancer or gastroesophageal junction cancer (GC/GEJC) participants.
Do-Youn Oh and her team aimed to assess the efficacy of perioperative durvalumab and FLOT combination therapy. Pre-planned interim analysis (IA) results are reported.
The study performed an inclusive analysis involving patients (pts) with resectable (>T2 N0-3 M0/T0-4 N1-3 M0) GC/GEJC. Randomized at a 1:1 ratio, participants received either D 1500 mg or P every 4 weeks (Q4W) on Day 1, combined with FLOT Q2W on Days 1 and 15 for 4 cycles. This regimen included (2 doses of D or P and 4 doses of FLOT pre- and post-operatively), followed by D 1500 mg or P on Day 1 Q4W for 10 additional cycles.
Interim analysis (IA) occurred after all randomized pts underwent surgery or were precluded from it. The study assessed the superiority of the pathological complete response (pCR) rate (α=0.1% [2-sided]) through central review (Modified Ryan). Surgical and safety outcomes were also comprehensively evaluated.
About 474 pts with resectable (GC/GEJC) were randomized into each treatment arm. Baseline characteristics were balanced, with 19% of pts enrolled in Asia. The majority had gastric cancer (68%), cT3 (66%; cT4, 25%), and cLN+ (70%). The addition of D to FLOT demonstrated a statistically significant improvement in pCR compared to P (19% vs. 7%; Δ12%; OR, 3.08; P<0.00001).
The combined pCR/near-complete pathological response (pnCR) rate was 27% with D vs. 14% with P. Surgery rate and R0 resection rate (in pts who underwent surgery) were similar with D (87% and 86%, respectively) vs. P (84% and 86%, respectively). Downstaging favored D vs. P (pT0, 21% vs. 10%; pN0, 47% vs. 33%; by central review). Median D and P exposure was similar, and adverse event (AE) rates were comparable between arms.
The study concluded that the addition of D to perioperative FLOT therapy results in a clinically meaningful and statistically significant improvement in pCR for GC/GEJC, while maintaining a tolerable safety profile. The trial is ongoing for event free survival (EFS), and results are yet to be presented.
The study is sponsored by AstraZeneca
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/31
Clinical Trial: https://clinicaltrials.gov/study/NCT04592913
Oh D Y, Janjigian Y Y, Al-Batran S E, et al. (2023). “Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study.” Presented at ESMO ASIA 2023 (Abstract 129O).
