Adjuvant immunotherapies shift gastric cancer trt paradigm

Addition of indication for 'Imfinzi+FLOT' imminent

It has been confirmed to be used in combination with Tevimbra

Cancer immunotherapy 'Imfinzi'

Major immune checkpoint inhibitors have demonstrated effects in pre- and post-operative adjuvant therapy. A paradigm shift in the treatment of gastric cancer is expected.

According to industry sources on the 17th, the addition of an indication for the immunotherapy 'Imfinzi (durvalumab)' in advanced gastric cancer is imminent. AstraZeneca Korea anticipates approval within this month.

While East Asia is notable for excellent early diagnosis and surgical outcomes, the risk of recurrence due to residual micrometastases remains high for patients with Stage 2–3 locally advanced disease. A perioperative treatment strategy, administering anticancer drugs both before and after surgery, has emerged as a solution to improve clinical outcomes.

According to the final analysis of the Phase 3 MATTERHORN trial presented at the European Society for Medical Oncology (ESMO 2025) in Berlin last October, Imfinzi's perioperative adjuvant therapy significantly improved overall survival (OS) with statistical significance. Furthermore, clinical results for Asian patients, including South Koreans, were introduced at ESMO ASIA 2025.

A total of 180 Asian patients participated in this analysis. The Asian cohort had a higher proportion of high-risk patients, with a greater frequency of T4 staging and lymph node positivity compared to the overall study population.

Despite this, the Imfinzi combination therapy showed positive results, reducing the risk of disease progression by 26% in the event-free survival (EFS) endpoint compared with the placebo combination group. 

The 24-month EFS rate was 72.1% for the Imfinzi group, higher than the 64.2% in the placebo group. As the median EFS has not yet been reached in either group, the treatment benefit may become even more pronounced during long-term follow-up. The OS benefits were also consistent with the previous global clinical data.

A particularly striking result was the pathological complete response (pCR). In the Asian cohort, the Imfinzi combination increased the proportion of patients whose tumors completely disappeared at the time of surgery to 18.9%, more than triple the 5.6% recorded in the placebo group. 

This level is similar to the overall analysis results, demonstrating that Imfinzi can significantly enhance tumor shrinkage effects during the preoperative phase.

Safety was also confirmed to be at a manageable level, with no specific increase in toxicity compared to the standard FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen. There was no significant difference in Grade 3 or higher adverse events between the two groups, and treatment discontinuation rates were similar, indicating no new safety concerns arising from the addition of Imfinzi. Given that FLOT itself is an intensive regimen, this is interpreted as an important finding.

Based on these clinical results, the U.S. Food and Drug Administration (FDA) last month approved Imfinzi monotherapy as maintenance treatment following FLOT combination therapy in adult patients with resectable gastric and gastroesophageal junction adenocarcinoma.

While surgery remains the cornerstone of curative treatment for gastric cancer, there is a growing global consensus, including in Asia, that surgery alone is often insufficient for a full cure. The MATTERHORN study has shown that administering immunotherapy in combination with FLOT before surgery, followed by radical resection and subsequent treatment, can meaningfully improve long-term outcomes.

Clinical trials of major immunotherapies in perioperative adjuvant therapy

Cancer immunotherapy 'Keytruda'

The attempt to integrate immunotherapy into perioperative care is not limited to Imfinzi. 

Various studies combining different immunotherapies with chemotherapy are confirming the potential for expanding gastric cancer treatment strategies.

For example, improvements in preoperative pathological response rates have been reported in several studies, including studies involving avelumab + FLOT (MONEO), sintilimab + FLOT, toripalimab + SOX, and tislelizumab + SOX. Some studies are also exploring strategies that combine immunotherapy with anti-angiogenic agents or radiation therapy.

Recently, the potential to improve tumor response rates has also been identified in preoperative adjuvant strategies involving the PD-1 inhibitor Tevimbra (tislelizumab), further raising the possibility of expanding preoperative immunotherapy.

However, not all immunotherapies have achieved the same level of success.

MSD's Keytruda (pembrolizumab) demonstrated improved pCR in the Phase 3 KEYNOTE-585 study evaluating a perioperative adjuvant strategy but failed to improve EFS, thus failing to meet its primary endpoints.