Adding Imfinzi (durvalumab) to FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy before and after surgery improved event-free survival compared to placebo plus FLOT for patients with resectable gastric or or gastroesophageal junction (GEJ) adenocarcinoma, according to data from the phase 3 MATTERHORN trial.
Findings presented in a press briefing at the 2025 ASCO Annual Meeting showed that at a median follow-up of 31.6 months for the Imfinzi arm (474 patients) and 31.4 months for the placebo arm (474 patients), Imfinzi plus FLOT generated a median EFS that was not reached compared with 32.8 months for placebo plus FLOT. In the Imfinzi arm, the 18- and 24-month EFS rates were 73% and 67%, respectively. These respective rates were 64% and 59% in the placebo arm.
“The [EFS] benefit was seen across prespecified [subgroup] cohorts. We did not see any new safety signals. [Therefore], this will change practice for our patients, which is exciting to see,” lead study author Dr. Yelena Y. Janjigian, said in the press briefing.
Janjigian is chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center in New York, New York.
Safety of the Trial
Glossary:
Event-free survival (EFS): time during and after treatment that a patient lives without cancer progressing or surgery being delayed or canceled.
Overall survival (OS): time from treatment start or diagnosis until death from any cause.
Pathological complete response (pCR): no detectable cancer found in surgical tissue after treatment.
Disease-free survival (DFS): time after treatment during which a patient shows no signs of cancer.
R0 resection: surgery that removes all visible cancer with no cancer cells seen at the edges of the removed tissue.
PD-L1 (programmed death-ligand 1): a protein that helps cancer cells avoid being destroyed by the immune system.
ECOG performance status: scale used to measure how a patient's disease is affecting their daily living abilities.
Regarding safety, any-grade adverse effects (AEs; side effects) occurred in 99% of patients in both arms. The rates of AEs possibly related to study treatment were both 95%. The rates of grade 3/4 AEs were 72% for the Imfinzi arm versus 71% for the placebo arm. Grade 3 (severe)/4 (life-threatening) AEs possibly related to treatment occurred at rates of 60% and 59%, respectively. The rates of serious AEs were 48% for the Imfinzi arm versus 44% for the placebo arm.
AEs led to treatment discontinuation of any study treatment in 30% of patients in the experimental arm versus 23% of patients in the control arm. Ten percent of patients discontinued Imfinzi due to AEs, whereas 6% discontinued placebo. FLOT was discontinued due to AEs in 25% and 20% of patients, respectively.
AEs led to death in 5% of patients in the Imfinzi arm versus 4% of patients in the placebo arm. These AEs were deemed possibly related to Imfinzi or placebo in 1% and less than 1% of patients, respectively. AEs leading to death that were possibly related to FLOT occurred at respective rates of 1% and less than 1%.
Any-grade immune-mediated AEs (irAEs) were reported in 23% of patients in the Imfinzi group versus 7% of patients in the placebo arm. The rates of grade 3/4 irAEs were 7% and 4%, respectively.
Surgery was not performed due to AEs in 1% of patients in the experimental arm versus less than 1% of patients in the control arm. The rates of AEs leading to a delay in surgery were 2% and 3%, respectively.
Scaling the MATTERHORN
Investigators of the global, double-blind, placebo-controlled trial enrolled patients with stage 2 to 4a gastric/GEJ adenocarcinoma who had no evidence of metastases and received no prior therapy. Patients also needed to have an ECOG performance status of 0 or 1.
Patients were randomly assigned 1:1 to the Imfinzi or placebo arm. Neoadjuvant therapy lasted two cycles, comprising Imfinzi at 1500 milligrams (mg) once every four weeks plus FLOT or placebo plus FLOT. Following surgery, patients received 2 additional cycles of Imfinzi at 1500 mg once every four weeks plus FLOT, or placebo plus FLOT. Patients then received Imfinzi at 1500 mg once every four weeks or placebo as monotherapy for 10 additional adjuvant cycles.
Key stratification factors included region (Asia versus non-Asia), clinical stage (N+ versus N–), and PD-L1 status (tumor area positivity [TAP] less than 1% versus TAP more than or equal to 1%).
EFS served as the trial’s primary end point. Overall survival (OS), pathological complete response (pCR) rate, and disease-free survival (DFS) were key secondary end points.
All patients in the Imfinzi arm received any neoadjuvant treatment compared with 99% of patients in the placebo arm. Neoadjuvant treatment with Imfinzi or placebo was completed in 97% and 95% of patients, respectively. The respective rates of patients who completed neoadjuvant FLOT were 96% and 95%.
Surgery was attempted in 91% of patients in the Imfinzi arm versus 90% of those in the placebo arm. Surgery was completed in 87% and 84% of patients, respectively. The rates of R0 resection were 92% in both arms. Any adjuvant therapy was given to 77% of patients in the Imfinzi group versus 74% of patients in the placebo group. Fifty-two percent of patients in both arms completed adjuvant Imfinzi or placebo; 61% and 64%, respectively, completed adjuvant FLOT. At the data cutoff, 68% of patients in the Imfinzi arm and 59% of patients in the placebo arm were actively in follow-up.
At baseline, the median age was 62 years in the Imfinzi arm versus 63 years in the placebo arm. The majority of patients in both groups were male (Imfinzi, 69%; placebo, 75%), from regions outside of Asia (81%; 81%), had an ECOG performance status of 0 (71%; 77%), had gastric tumors (68%; 67%), had non-T4 disease (75%; 75%), had node-positive disease (69%; 70%), had a PD-L1 TAP of at least 1% (90%; 90%), had an intestinal histology (52%; 50%), and did not have microsatellite instability–high disease (64%; 65%).
Secondary End Points
The median OS was NR in the Imfinzi arm versus 47.2 months in the placebo arm. The 18- and 24-month OS rates were 81% and 76%, respectively, in the Imfinzi arm. These respective rates were 77% and 70% in the placebo arm. The median follow-up for OS was 34.6 months in the Imfinzi group versus 34.6 months in the placebo group.
Patients in the Imfinzi arm achieved a pCR rate of 19% compared with 7% for those in the placebo arm, translating to a 12% difference.
The median DFS was NR in the Imfinzi arm versus 39.8 months in the placebo arm. The 18- and 24-month DFS rates were 79% and 75%, respectively, for Imfinzi plus FLOT versus 73% and 66%, respectively, for placebo plus FLOT.
Patients in both arms received a median of two neoadjuvant cycles of Imfinzi/placebo and FLOT. They received a median of 12 adjuvant cycles of Imfinzi/placebo and a median of two adjuvant cycles of FLOT. All patients received at least one neoadjuvant cycle of Imfinzi/placebo plus FLOT. Exactly two cycles of neoadjuvant Imfinzi and FLOT were each given to 97% of patients in the experimental arm; these rates were both 96% in the control arm.
In the experimental arm, at least one cycle of adjuvant Imfinzi and FLOT was given to 76% and 75% of patients, respectively. The rates of patients who received at least two cycles of each were 73% and 67%, respectively. Seventy-two percent of patients received at least three cycles of adjuvant Imfinzi, and 52% received 12 cycles. In the control arm, at least one cycle of adjuvant placebo and FLOT was given to 74% of patients each. Seventy-two percent received at least two placebo cycles, and 68% completed two adjuvant FLOT cycles. Seventy-one percent of patients completed at least three cycles of adjuvant placebo, and 51% completed the full 12-cycle adjuvant placebo course.
Reference:
“Event-free survival in MATTERHORN” by Dr. Yelena Janjigian, et al., Journal of Clinical Oncology
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