Durvalumab plus chemo for GC/GEJC delivers globally consistent benefit

Combination treatment with durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) leads to higher rates of pathologic complete response (pCR) in patients with resectable gastric cancer (GC) or gastroesophageal junction cancer (GEJC), with the benefit universally observed regardless of geographic location, according to the subgroup analysis of the phase III MATTERHORN study.

Primary analysis already indicated that adding durvalumab to FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) was associated with a threefold increase in the likelihood of achieving pCR as compared with placebo plus FLOT in the global population (19 percent vs 7 percent; odds ratio [OR], 3.08, 95 percent confidence interval [CI], 2.03–4.67). [ESMO 2023, abstract 129O]

In the current subgroup analysis, the Asia cohort responded equally well to durvalumab plus FLOT as the non-Asia cohort, with the pCR rate improving by 13 percent (OR, 3.96, 95 percent CI, 1.39–11.26) and 12 percent (OR, 2.92, 95 percent CI, 1.85–4.61), respectively, relative to placebo plus FLOT. This held true despite the fact that Asians were more likely to have unfavourable baseline characteristics such as poor performance status, lymph node positivity, and T4 stage tumours, reported lead researcher Dr Yelena Janjigian of Memorial Sloan Kettering Cancer Center in New York City, New York, US. [ASCO GI 2024, abstract LBA246]

Within the non-Asia cohort, the pCR rates consistently favoured durvalumab over placebo across patients from Europe (18 percent vs 8 percent; OR, 2.45, 95 percent CI, 1.42–4.24), North America (29 percent vs 8 percent; OR, 4.93, 95 percent CI, 1.27–19.10), and South America (17 percent vs 5 percent; OR, 3.76, 95 percent CI, 1.30–10.84). This consistency, according to Janjigian, was very reassuring to see.

“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,” with the findings demonstrating the same trend of improvement in complete pathologic response with the addition of durvalumab regardless of geographic location, Janjigian said.

She also stressed that FLOT is a feasible treatment approach for patients around the world, based on the observation that most patients were able to complete the treatment protocol, with 97 percent having preoperative FLOT and 63 percent having adjuvant FLOT completed.

MATTERHORN included 948 patients in total, of whom 53 percent were from Europe, 19 percent from Asia, 19 percent from South America, and 9 percent from North America. These patients were randomly assigned to receive four doses of FLOT plus two doses of durvalumab or placebo before and after the surgery, followed by 10 doses of durvalumab or placebo as maintenance.

The combined complete and near-complete pathologic response rate was also significantly higher in the durvalumab than in the placebo group (27 percent vs 14 percent; OR, 2.19; p<0.00001). Almost all prespecified subgroups benefitted from the addition of durvalumab, including the microsatellite instability (MSI)-high and non–MSI-high subgroups, except for patients with very low levels of PD-L1 expression (less than 1 percent).

Janjigian shared that MATTERHORN is ongoing and that they are waiting for data on the primary endpoint of event-free survival to mature.