Osimertinib in combination with durvalumab demonstrated encouraging clinical activity, but the combination was associated with high rates of toxicities, a study presented at the European Lung Cancer Conference (ELCC) 2016 has shown.1
Osimertinib is a potent, selective, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has demonstrated efficacy in tumors with EGFR mutations and T790M resistance mutations. Durvalumab is a selective, IgG1 monoclonal antibody that blocks programmed death-ligand 1 (PD-L1) and CD80 with high affinity.
Researchers designed the multi-arm, phase 1b TATTON trial to assess the efficacy, tolerability, and safety of the combination. The study was conducted in 2 parts: dose escalation in EGFR-TKI pre-treated patients and dose expansion in EGFR-TKI treatment-naïve patients. All participants received osimertinib 80 mg orally daily plus durvalumab 3 mg/kg or 10 mg/kg intravenously every 2 weeks during the dose-escalation part or 10 mg/kg every 2 weeks during the dose-expansion portion.
In terms of efficacy, 12 patients in the dose-escalation part and 8 in the dose-expansion part achieved a partial response. Nine and 2, respectively, had stable disease.
The most common adverse events were nausea (39%), vomiting (39%), anemia (35%), and diarrhea (35%) among the 23 patients treated in the dose-escalation portion. The most frequently reported adverse events among the 11 treated in the dose-expansion phase were interstitial lung disease (64%), diarrhea (55%), and nausea (45%).
In total, approximately 38% of patients developed interstitial lung disease, of which 5 cases were grade 3 or 4. Most cases of interstitial lung disease were managed with corticosteroids and there were no fatalities. The median time to onset of interstitial lung disease was 69 days.
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Because there appeared to be an increased incidence of interstitial lung disease with the combination of osimertinib and durvalumab compared with either agent alone, this arm is currently on hold.
- Ahn M, Yang J, Yu H, et al. Osimertinib combined with durvalumab in EGFR-mutant non-small cell lung cancer: results from the TATTON phase 1b trial. Oral presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.