Durvalumab Approved for Resectable Gastric and Gastroesophageal Junction Adenocarcinoma
Expert Perspectives
By Lyn Brook
Published
The FDA has approved durvalumab (Imfinzi®, AstraZeneca) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as neoadjuvant and adjuvant therapy, followed by durvalumab monotherapy, for adults with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). This approval establishes a new perioperative immunotherapy–chemotherapy approach for stage II–IVA, resectable disease.
Why This Approval Matters
Patients with resectable GC/GEJC face high rates of recurrence despite multimodality therapy. Perioperative FLOT has become a key standard of care, but long-term outcomes remain suboptimal. Adding durvalumab to FLOT in both the pre‑ and postoperative settings significantly improved event‑free survival (EFS) and increased pathologic complete response (pCR) rates compared with FLOT alone, suggesting deeper tumor eradication and more durable disease control. This regimen provides a new option that builds on an established chemotherapy backbone without requiring a change in surgical strategy.
Breaking Down MATTERHORN
Efficacy was studied in the MATTERHORN trial (NCT04592913)—a phase 3, double‑blind, placebo‑controlled, multicenter trial that enrolled 948 patients with previously untreated, resectable stage II-IVA GC/GEJC.
Patients were randomized 1:1 to receive:
- Experimental arm: Durvalumab plus FLOT in the neoadjuvant and adjuvant settings, followed by durvalumab monotherapy.
- Control arm: Placebo plus FLOT in the same perioperative schedule.
The primary end point was EFS as assessed by blinded independent central review. Key secondary end points included overall survival (OS) and pCR rate per blinded central pathology review. The trial was not designed to isolate the relative effects of durvalumab in the neoadjuvant versus adjuvant phases of treatment.
Results showed:
- EFS: Median EFS was not reached in the durvalumab plus FLOT arm versus 32.8 months in the placebo plus FLOT arm.
- OS: Median OS was not reached in both arms, indicating an emerging survival benefit.
- pCR: The pCR rate was 19.2% with durvalumab plus FLOT versus 7.2% with placebo plus FLOT, reflecting a marked increase in complete tumor clearance at the time of surgery.
Managing Adverse Events
The durvalumab prescribing information carries warnings and precautions consistent with other PD‑L1 inhibitors, including:
- Immune‑mediated adverse reactions
- Infusion‑related reactions
- Complications of allogeneic hematopoietic stem cell transplantation
- Embryo‑fetal toxicity
Dosing and Administration
For adults with body weight ≥30 kg:
- Neoadjuvant and adjuvant combination phase: Durvalumab 1,500 mg IV every four weeks with FLOT for up to four cycles total (across the pre‑ and postoperative settings).
- Adjuvant monotherapy phase: Durvalumab 1,500 mg IV every four weeks for up to 10 additional cycles.
For patients with body weight <30 kg:
- Neoadjuvant and adjuvant combination phase: Durvalumab 20 mg/kg IV every four weeks with FLOT for up to four cycles total.
- Adjuvant monotherapy phase: Durvalumab 20 mg/kg IV every four weeks for up to 10 additional cycles.
Treatment is continued until disease progression, recurrence, unacceptable toxicity, or completion of a maximum of 12 cycles after surgery.
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