MATTERHORN is a Phase III international study on the use of immunotherapy in combination with chemotherapy for gastric cancer and esophageal–gastric junction
The positive results of the intermediate analysis of the data of the phase III MATTERHORN study showed that the addition of durvalumab to the standard scheme of neoadjuvant chemotherapy FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) provides a statistically and clinically significant increase in the frequency of complete pathomorphological response (pPO) (a key secondary endpoint) compared with the use of only neoadjuvant chemotherapy in patients with operable cancer of the stomach or esophageal-gastric junction (esophageal-gastric junction) - early or locally advanced stages (stages II, III, IVA).
The study will continue to assess event-free (BSV) and overall survival.
The safety and tolerability of durvalumab in combination with neoadjuvant chemotherapy FLOT corresponds to the profile established for this combination. Compared with the use of chemotherapy alone, when durvalumab was added to neoadjuvant chemotherapy, the number of patients with indications for surgical treatment did not decrease.
Josep Tabernero, MD, PhD, Head of the Department of Therapeutic Oncology at the Val d'Hebron University Clinic, Spain, Chief Researcher of MATTERHORN, said: "Patients with operable stomach cancer and esophageal-gastric junction are in urgent need of more effective treatment methods, since today about 25% of patients face progression of the disease within a year after radical surgical intervention. The results of the study demonstrate an increase in the frequency of a complete pathomorphological response after the addition of durvalumab to neoadjuvant chemotherapy FLOT and radical surgery. The results obtained mean that the use of the new scheme can provide a long-term clinical advantage in such patients, since the frequency of a complete pathomorphological response correlates with both event-free and overall survival at various stages of the disease."
Susan Galbraith, Executive Vice President and Head of Research and Development in the Field of Oncology at AstraZeneca, noted: "The preliminary results of the MATTERHORN study confirm that the effect on the immune system due to chemotherapy and surgery can become a new word in the treatment of stomach cancer and esophageal-gastric transition of early stages and improve the prognosis in such patients. The results obtained strengthen our commitment to develop innovative therapeutic solutions based on durvalumab, which will be able to change approaches to the treatment of cancer of the gastrointestinal tract."
Stomach cancer ranks fourth in the world in the structure of cancer mortality. Every year, more than one million new cases are detected in the world.
MATTERHORN is an international multicenter, randomized, double—blind, placebo-controlled phase III trial to evaluate the use of durvalumab as perioperative therapy in patients with operable gastric cancer or stage II–IVA pancreatic cancer. Perioperative therapy includes treatment before and after surgery — neoadjuvant and adjuvant therapy, respectively. The study included 958 patients who received a fixed dose of durvalumab (1500 mg) in combination with FLOT chemotherapy or placebo in combination with FLOT chemotherapy 1 time every 4 weeks for 2 cycles before surgery, followed by the use of durvalumab or placebo 1 time every 4 weeks (up to 12 cycles) after surgery (including 2 durvalumab or placebo cycles in combination with FLOT chemotherapy and 10 more cycles of durvalumab or placebo monotherapy).
The primary endpoint in the MATTERHORN study is BSV, that is, the time from randomization to the onset of disease progression or death. Key secondary endpoints include the frequency of pPO, that is, the proportion of patients who have no tumor cells detected in the removed tumor tissue after neoadjuvant therapy, and overall survival(s). The study involved patients from 176 centers in 20 countries, including Russia, the USA, Canada, Europe, South America and Asia.
Durvalumab is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with PD-1 and CD80 proteins, counteracting the evasion of the tumor from the immune system and enhancing the immune response.
According to the results of phase III studies of TOPAZ-1, durvalumab has been registered in Russia for use in combination with chemotherapy for locally advanced and metastatic cancer of the biliary tract. Also, according to the results of the HIMALAYA study, durvalumab is approved in the USA, the EU, Japan and a number of other countries for use in combination with tremelimumab in inoperable hepatocellular cancer (HCC).
In addition to indications for use in oncological diseases of the gastrointestinal tract (gastrointestinal tract), durvalumab (based on the results of the PACIFIC Phase III study) is the only immunotherapeutic drug registered for the radical treatment of inoperable non-small cell lung cancer (NSCLC) stage III in patients without disease progression after chemoradiotherapy. Durvalumab is the world standard of therapy for this disease.
In addition, according to the results of the CASPIAN Phase III study, durvalumab is approved in Russia, the USA, the EU, Japan, China and many other countries for the treatment of advanced small cell lung cancer (MRL). According to the results of the phase III POSEIDON study, the combination of durvalumab with a short course of tremelimumab and chemotherapy is approved for the treatment of metastatic NSCLC in the USA, EU countries and Japan.
Since the first registration in May 2017, more than 200,000 patients have received treatment with durvalumab.
As part of an extensive clinical research program, the use of durvalumab is being studied as monotherapy and in combination with other antitumor drugs in patients with MRL, NSCLC, bladder cancer, some types of malignant gastrointestinal tumors, ovarian cancer, endometrial cancer and other solid tumors.
Currently, AstraZeneca is conducting several registration studies to evaluate durvalumab in the treatment of various gastrointestinal oncological diseases: liver cancer of various stages (EMERALD-1, EMERALD-2 and EMERALD-3 studies) and locally advanced esophageal cancer (KUNLUN study).