Durvalumab Plus FLOT Chemotherapy Achieves 60% Pathological Complete Response in Resectable Gastric and Gastroesophageal Junction Cancer: Interim Results from Phase 3 MATTERHORN Trial Presented at ESMO 2023

Oct 18, 2023 15:19 CST Updated 15:19

AstraZeneca

Biopharmaceutical Manufacturer

The 2023 ESMO Annual Meeting is set to take place from October 20 to 24 in Madrid, Spain, with the detailed agenda already published on the conference's official website. Prior to the LBA release, many well-known pharmaceutical companies plan to announce via press releases whether some key clinical trials have met their primary or secondary endpoints.

Here, the Mece Oncology New Frontier has compiled one of the LBAs that has officially announced positive results and is worth paying attention to.

LBA73——MATTERHORN

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 3 MATTERHORN study.

Pathological Complete Response to Durvalumab Plus 5-Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel in Resectable Gastric and Gastroesophageal Junction Cancer: Interim Results from the Global Phase III MATTERHORN Study.

Gastric cancer is the fourth leading cause of cancer death globally, with more than 1 million people diagnosed each year. By 2030, there will be approximately 70,000 newly diagnosed patients with stage II-III gastric cancer or GEJ adenocarcinoma in the United States, the European Union, and Japan. About one-quarter of gastric cancer patients experience disease recurrence within one year after surgical treatment. There remains a significant unmet medical need in the field of gastric cancer.

The World’s First Phase III Immunotherapy and Chemotherapy Combination Trial – Redefining Gastrointestinal Cancer Treatment

On June 2, 2023, AstraZeneca announced the interim analysis results of the Phase III MATTERHORN trial, which is designed to evaluate the efficacy of durvalumab in the perioperative treatment of patients with stage II-IVA gastric cancer and gastroesophageal junction cancer.

The research results show that in patients with early and advanced gastric cancer and gastroesophageal junction adenocarcinoma,Durvalumab combined with chemotherapy achieved a significant improvement in the key secondary endpoint of pathological complete response (pCR) compared to neoadjuvant chemotherapy FLOT alone.`, this result is statistically and clinically significant.`

The MATTERHORN trial is a randomized, double-blind, placebo-controlled multicenter global Phase III trial. A total of 948 patients were randomly assigned to two groups, one receiving 1500 mg of durvalumab every 4 weeks in combination with FLOT chemotherapy before surgery, and the other receiving placebo in combination with FLOT chemotherapy.

The treatment regimen includes two cycles of preoperative therapy and up to 12 cycles of postoperative therapy, comprising two cycles of durvalumab or placebo in combination with FLOT, followed by 10 cycles of durvalumab or placebo monotherapy. The primary endpoint of the study is event-free survival (EFS), while key secondary endpoints include pathological complete response (pCR) and overall survival (OS).

The results of this study indicate that,Durvalumab Shows Potential Clinical Benefits in the Perioperative Treatment of Gastric Cancer and Gastroesophageal Junction Adenocarcinoma, Offering a New Therapeutic Option for These PatientsFurther research and analysis will help to better understand the efficacy and safety of Durvalumab.

AstraZeneca announced the results of the MATTERHORN Phase 3 study at this year's ASCO conference, marking a significant breakthrough for patients with resectable, early-stage, and locally advanced (Stage II, III, IVa) gastric cancer and gastroesophageal junction (GEJ) cancer. The study found that compared to neoadjuvant chemotherapy alone, preoperative combination chemotherapy demonstrated a statistically and clinically significant improvement in the key secondary endpoint of pathological complete response (pCR). This outcome indicates important progress in the field of gastric cancer treatment.

What is Imfinzi?

Imfinzi (durvalumab) is a humanized monoclonal antibody. By binding to PD-L1, Imfinzi blocks the interaction between PD-L1 and PD-1 and CD80 proteins, thereby inhibiting the tumor's immune escape mechanism. Imfinzi has been approved in many countries and regions, including the United States, China, and the European Union, for the treatment of patients with advanced bladder cancer.

Based on the results of the TOPAZ-1 and HIMALAYA Phase III clinical trials, Imfinzi has been approved in multiple countries, including the United States, the European Union, and Japan, as a combination chemotherapy agent (gemcitabine + cisplatin) for the treatment of locally advanced or metastatic biliary tract cancer (BTC), and in combination with Imjudo (tremelimumab) for the treatment of unresectable hepatocellular carcinoma (HCC).

In addition to its indications in gastrointestinal (GI) cancers, Imfinzi has also become the only globally approved immunotherapy as a curative treatment for patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed after chemoradiotherapy, establishing itself as the standard of care.

The subsequent trial results of MATTERHORN will be even more anticipated.

Patients with resectable gastric cancer and gastroesophageal junction cancer urgently need more effective treatment options, as even after radical surgery, one-quarter of patients experience disease progression within a year. However, by adding durvalumab to FLOT chemotherapy and surgery, the pathological complete response rate has improved. This encouraging early sign suggests that the regimen may offer long-term clinical benefits for these patients, as pathological complete response correlates with progression-free survival and overall survival in many cases.

These preliminary results from the MATTERHORN study support combining immunotherapy with chemotherapy and surgery as a new treatment approach to improve outcomes for patients with early-stage gastric cancer and gastroesophageal junction cancer. These findings further reinforce our focus on adopting novel treatment strategies based on Imfinzi, which may redefine the treatment landscape for patients with gastrointestinal cancers. We look forward to future results from the MATTERHORN study, which will be an exciting step toward further breakthroughs!

In August this year, the NCCN officially released the 2023 V2 edition of the gastric cancer diagnosis and treatment guidelines. This update focuses on gastric cancer patients with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR), adding new treatment options for perioperative treatment in the early stage as well as first-line and second-line treatments in the advanced stage.FreeEpidemic therapy becomes the key to gastric cancer treatment!

Imjudo + Durvalumab

At the 2023 ASCO Gastrointestinal Symposium, researchers announced the results of using Imjudo + durvalumab as neoadjuvant therapy for gastric cancer. The study showed,After treatment with Imjudo + durvalumab,The pathological complete response (pCR) rate of the patients was 60%.，The main complete pathological remission rate reached 80%.

Editor: Potato