Subgroup analyses of the randomized double-blind phase III MATTERHORN trial continue to show the benefit of adding perioperative durvalumab to standard chemotherapy in patients with locally advanced, resectable gastric or gastroesophageal junction cancer. Detailed findings on pathologic complete response were reported at the 2024 ASCO Gastrointestinal Cancers Symposium by Yelena Y. Janjigian, MD, of Memorial Sloan Kettering Cancer Center (Abstract LBA246).
“MATTERHORN is the first global phase III study that successfully randomized patients [with resectable gastric and gastroesophageal junction cancer] to receive perioperative durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel). We’ve demonstrated that the addition of durvalumab showed consistent improvement in pathologic complete responses over placebo, across the globe,” Dr. Janjigian said.
Yelena Y. Janjigian, MD
FLOT chemotherapy is a perioperative standard of care in operable gastric or gastroesophageal junction cancer based on the findings of the FLOT4 trial, and PD-1 blockade plus chemotherapy has become standard first-line therapy in metastatic disease. MATTERHORN evaluated the anti–PD-1 agent durvalumab given with FLOT in 948 patients with locally advanced, resectable gastric or gastroesophageal junction cancer.
In the previously reported interim analysis, the addition of durvalumab significantly improved the pathologic complete response rate by an absolute difference of 12%: rates were 7% with FLOT and 19% with durvalumab plus FLOT (odds ratio [OR] = 3.08, P < .00001). Dr. Janjigian’s presentation at the ASCO Gastrointestinal Cancers Symposium took a deeper dive into this outcome, with results according to region, country, and subgroups, thus generating some idea as to the global applicability of this approach.
More About MATTERHORN
Patients were recruited from Europe (53%), Asia (19%), South America (19%), and North America (9%) and were stratified by geographic region (specifically, Asia vs all other regions). They were randomly assigned to receive four doses of FLOT plus two doses of durvalumab or placebo preoperatively; after surgery, they received these same regimens again, followed by 10 doses of durvalumab or placebo as maintenance. The primary endpoint was event-free survival; these results are pending.
Durvalumab plus FLOT showed a statistically significant improvement in pathologic complete response. These were achieved by 19% of patients in the durvalumab/FLOT arm vs 7% of the FLOT-only arm, an absolute 12% improvement (OR = 3.08, P < .00001). The combined complete and near-complete pathologic response rate was also significantly improved—by 12%—based on rates of 27% in the durvalumab arm and 14% in the placebo arm (OR = 2.19, P < .00001), Dr. Janjigian reported.
In the exploratory analysis, virtually all prespecified subgroups derived benefit from the addition of durvalumab, with the exception of patients with PD-L1 expression of < 1%. Benefit was seen in both microsatellite instability (MSI)-high and non–MSI-high subgroups.
Consistent Benefit Across Regions and Subgroups
Dr. Janjigian noted that the addition of durvalumab to perioperative FLOT produced consistent improvements in pathologic complete response rates across geographic regions. At baseline, the Asian population had a higher percentage of patients with poor performance status, lymph-node positivity, and T4 stage tumors, but the benefit achieved with durvalumab was nearly identical to that of the non-Asian populations: absolute improvements were 13% (OR = 3.96) and 12% (OR = 2.92), respectively, she reported.
These improvements in pathologic complete response were also consistent across the European (a 10% improvement) and South American cohorts (a 12% improvement), and actually increased (a 21% improvement) in the North American cohort (OR = 4.93), she added.
Also of note, a higher percentage of individuals treated with durvalumab plus FLOT achieved T0 stage (23% vs 11%) and N0 stage (52% vs 36%) after surgery. The study also showed that, globally, “FLOT is feasible,” Dr. Janjigian added, based on the observation that 97% of patients completed preoperative treatment and 63% completed adjuvant therapy.
Disclosure: Dr. Janjigian has received fees for consulting and travel from AmerisourceBergen, Arcus Biosciences, AstraZeneca, Basilea Pharmaceutica, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Geneos Therapeutics, GlaxoSmithKline, Imedex, Imugene, Lynx Health, Merck, Merck Serono, Michael J. Hennessy Associates, Paradigm Medical Communications, PeerView Institute, Pfizer, RGENIX, Seagen, Silverback Therapeutics, and Zymeworks and has stock options with RGENIX.
