KEY TAKEAWAYS
- The MATTERHORN phase 3 trial aimed to investigate the global efficacy of perioperative D with FLOT in GC/GEJC.
- Researchers conclude that a consistent improvement in pCR was observed in enhancing perioperative FLOT treatment for GC/GEJC; trial is ongoing for the EFS.
5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) emerged as a promising perioperative therapy for gastric and gastroesophageal junction cancer (GC/GEJC) based on the Phase 2/3 FLOT4 study in Germany, revealing a 16% pathological complete response (pCR) rate (Al-Batran et al, Lancet Oncol 2016). Building on this foundation, the global MATTERHORN study demonstrated a significant advancement in pCR when combining Durvalumab (D) with perioperative FLOT compared to placebo (P) + FLOT during the initial interim analysis (Janjigian et al, ESMO Congress 2023). Subgroup analyses were conducted across diverse regions and countries to comprehensively evaluate pCR rates with FLOT.
Yelena Y. Janjigian and her team aimed to assess the global effectiveness of perioperative Durvalumab in combination with FLOT.
They comprehensively analyzed participants with resectable GC/GEJC, employing a 1:1 randomization to receive either D at a dose of 1500 mg or P every 4 weeks (Q4W) on Day 1. This was accompanied by FLOT Q2W on Days 1 and 15 for 4 cycles ( 2 doses of D or P and 4 doses of FLOT, pre- and post-operatively). Subsequently, participants received D 1500 mg or P on Day 1 Q4W for an additional 10 cycles. Stratification during randomization was based on geographical location, distinguishing between Asia vs non-Asia regions. pCR (Modified Ryan; central review) was assessed in prespecified (Asia) and post hoc regional subgroups. This analysis included 6 countries with the highest numbers of randomized patients (pts).
About 948 participants were globally randomized, with 180 individuals (19%) representing the Asian region. pCR outcomes with FLOT in Asia mirrored global outcomes. Across all regions (Asia, Europe, North America, and South America), pCR rates demonstrated improvement with D + FLOT vs P + FLOT. Noteworthy was the consistency of these results despite baseline characteristic imbalances and numerical differences in pCR rates across geographic locations.
In the German subgroup, the pCR rate with P + FLOT stood at (13%; 95% CI, 6.1–23.0), resembling the pCR rate observed with FLOT in the FLOT4 study. Improvement in pCR with D + FLOT vs P + FLOT was observed across subgroups, irrespective of country. This trend extended to combined complete and near-complete response (CR) rates, with similar patterns observed across regional subgroups.
The study concluded that the consistent improvement in pCR observed with the addition of D to perioperative FLOT in GC/GEJC across diverse geographic regions underscores the potential efficacy of this combination. The investigation is ongoing, primarily focusing on event-free survival (EFS).
The study is sponsored by AstraZeneca
Source: https://meetings.asco.org/abstracts-presentations/229135
Clinical Trial: https://clinicaltrials.gov/study/NCT04592913
Janjigian Y Y, Al-Batran S E, Wainberg Z A, et al. (2023). “Pathological complete response (pCR) to 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) with or without durvalumab (D) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Subgroup analysis by region from the phase 3, randomized, double-blind MATTERHORN study.” Presented at ASCO-GI 2024 (Abstract LBA246).
