Rapid Readout: T-DXd in Patients With HER2+ Unresectable or Metastatic Gastric or GEJ Following a Trastuzumab-Containing Regimen

Ronan Kelly, MD, MBA, discusses data from the presentation “Primary analysis of a phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer who progressed on or after a trastuzumab-containing regimen.” (Van Cutsem et al, ESMO 2021, LBA55)

  • Overexpression and/or amplification of HER2 occurs in approximately 20% of gastric or gastroesophageal junction (GEJ) cancers.
  • DESTINY-Gastric02 trial is a single-arm, phase 2 study of trastuzumab deruxtecan (T-DXd) in second-line therapy in Western patients with HER2+ gastric/GEJ cancer.
  • Methods
    • Patients with centrally confirmed HER2+ (IHC3+ or IHC2+/ISH+ biopsy after trastuzumab-based therapy) unresectable/metastatic gastric/GEJ cancer who progressed on or after trastuzumab-containing 1L therapy were treated with T-DXd 6.4 mg/kg intravenously every 3 weeks.
    • The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by independent central review (ICR).
    • Progression-free survival (PFS), duration of response by ICR, and safety were secondary end points.
  • Results
    • Between Dec 2019 and Apr 2021, 79 patients from the US/EU with a median 1.0 (range 1-2) prior therapies were treated with T-DXd for a median of 4.3 months (range 0.7-15.9).
      • Median duration of follow-up was 5.7 months (range 0.7-15.2).
      • Median age was 61 years (range 20-78).
    • Efficacy results
      • Confirmed ORR by ICR was seen in 30 patients (38%, 95% CI, 27.3-49.6).
      • Complete response was seen in 3 patients (3.8%), partial response in 27 (34.2%), stable disease in 34 (43.0%) and progressive disease was seen in 13 (16.5%) patients.
      • Median PFS was 5.5 months (95% CI, 4.2-7.3)
      • Median duration of response was 8.1 months (95% CI, 4.1-NE)
      • Median time to response was 1.4 months (95% CI, 1.4-2.6)
    • Safety results
      • Any grade treatment-emergent adverse events (AEs) were seen in 74 patients (93.7%) while grade 3 or higher AEs were seen in 21 patients (26.6%).
      • The most common TEAEs were nausea (58.2%), fatigue (36.7%) and vomiting (32.9%).
      • Adjudicated drug-related interstitial lung disease occurred in 6 (7.6%) patients (grade 1-2, 5 patients; grade 5, 1 patient).
      • AEs were associated with dose discontinuation in 7 (8.9%) and dose reduction in 15 patients (19.0%).
  • Conclusions
    • T-DXd demonstrated clinical efficacy and a manageable safety profile in second-line treatment of Western patients with HER2+ unresectable/metastatic gastric/GEJ cancer.