Is Durvalumab Approved for Gastric Cancer?
Yes, durvalumab is now FDA-approved for gastric cancer in the perioperative setting when combined with FLOT chemotherapy for resectable gastric or gastroesophageal junction adenocarcinoma. 1, 2
Current FDA Approval Status
Durvalumab received FDA approval based on the landmark MATTERHORN trial, which demonstrated that perioperative durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) significantly improved event-free survival compared to FLOT alone in patients with resectable gastric or gastroesophageal junction adenocarcinoma. 1 The trial showed:
- Two-year event-free survival: 67.4% with durvalumab versus 58.5% with placebo (HR 0.71; 95% CI 0.58-0.86; P<0.001) 1
- Pathological complete response rate: 19.2% with durvalumab versus 7.2% with placebo (relative risk 2.69; 95% CI 1.86-3.90) 1
- Two-year overall survival: 75.7% with durvalumab versus 70.4% with placebo 1
Approved Treatment Regimen
The FDA-approved regimen consists of:
- Neoadjuvant phase: Durvalumab 1500 mg every 4 weeks plus FLOT for 2 cycles 1
- Surgery: Gastrectomy performed after neoadjuvant therapy 1
- Adjuvant phase: Durvalumab 1500 mg every 4 weeks plus FLOT for 2 cycles, followed by durvalumab monotherapy every 4 weeks for 10 additional cycles 1
What Durvalumab Is NOT Approved For
Durvalumab is NOT approved for metastatic or unresectable gastric cancer. 3 The NCCN guidelines do not list durvalumab as a treatment option for advanced/metastatic gastric cancer, instead recommending:
- First-line for HER2-negative, PD-L1 CPS ≥5: Nivolumab plus chemotherapy (Category 1) 3, 4
- Second-line or later for MSI-H/dMMR: Pembrolizumab or dostarlimab-gxly 3, 4
- Third-line in Japan only: Nivolumab monotherapy (not FDA-approved in US for this indication) 4
Historical Context
Prior to the MATTERHORN approval, durvalumab was only FDA-approved for urothelial carcinoma and non-small cell lung cancer, not gastric cancer. 3 Earlier phase I/II studies explored durvalumab in combination with ramucirumab for previously treated gastric cancer, showing manageable safety but these were investigational only. 5 The PRODIGE 59-DURIGAST trial evaluated durvalumab plus FOLFIRI in second-line metastatic gastric cancer, but this remains investigational. 6
Safety Profile
Grade 3-4 adverse events occurred in 71.6% of patients receiving durvalumab plus FLOT versus 71.2% with FLOT alone, indicating the combination does not substantially increase severe toxicity. 1 Importantly:
- Delayed surgery occurred in 10.1% with durvalumab versus 10.8% with placebo 1
- Delayed adjuvant treatment initiation: 2.3% with durvalumab versus 4.6% with placebo 1
Critical Caveat
This approval applies ONLY to resectable disease in the perioperative setting. 1, 2 For patients presenting with metastatic gastric cancer, durvalumab should not be used; instead, follow NCCN guidelines recommending nivolumab (for PD-L1 CPS ≥5) or pembrolizumab (for MSI-H/dMMR tumors) combined with appropriate chemotherapy backbones. 3, 4