Osimertinib Plus Durvalumab versus Osimertinib Monotherapy in EGFR T790M–Positive NSCLC following Previous EGFR TKI Therapy: CAURAL Brief Report
Journal
Journal of Thoracic Oncology
Journal Volume
14
Journal Issue
5
Pages
933-939
Date Issued
2019
Author(s)
Shepherd F.A
Kim D.-W
Lee G.-W
Lee J.S
Chang G.-C
Lee S.S
Wei Y.-F
Lee Y.G
Laus G
Collins B
Pisetzky F
Horn L.
Abstract
Introduction: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor (TKI). Durvalumab is an anti–programmed death ligand 1 monoclonal antibody. The phase III open-label CAURAL trial (NCT02454933) investigated osimertinib plus durvalumab versus osimertinib monotherapy in patients with EGFR-TKI sensitizing and EGFR T790M mutation–positive advanced NSCLC and disease progression after EGFR-TKI therapy. Methods: Patients were randomly assigned 1:1 to receive orally administered osimertinib (80 mg once daily) with or without durvalumab (10 mg/kg administered intravenously every 2 weeks) until progression. Treatment could continue beyond progression, providing clinical benefit continued (judged by the investigator). The amended primary objective was to assess the safety and tolerability of osimertinib plus durvalumab; efficacy was an exploratory objective. Results: CAURAL recruitment was terminated early because of increased incidence of interstitial lung disease–like events in the osimertinib plus durvalumab arm from the separate phase Ib TATTON trial (NCT02143466). At termination of CAURAL recruitment, 15 patients had been randomly assigned to treatment with osimertinib and 14 to treatment with osimertinib plus durvalumab. The most common AEs were diarrhea (53% [grade ?3 in 6% of patients]) in the osimertinib arm and rash (67% [grade ?3 in 0 patients]) in the combination arm. One patient who had been randomized to the combination arm reported grade 2 interstitial lung disease while receiving osimertinib monotherapy (after discontinuing durvalumab therapy after one dose). The objective response rates were 80% in the osimertinib arm and 64% in the combination arm. Conclusion: Limited patient numbers preclude formal safety and efficacy comparisons between the two treatment arms. The combination of programmed cell death 1/programmed death ligand 1 inhibitors and EGFR-TKIs as therapy for NSCLC is not well understood, but it requires a careful approach if considered in the future. ? 2019 International Association for the Study of Lung Cancer
Subjects
Combination; Durvalumab; EGFR; Non–small cell lung cancer; Osimertinib
SDGs
Other Subjects
aspartate aminotransferase; durvalumab; epidermal growth factor receptor kinase inhibitor; osimertinib; acrylamide derivative; aniline derivative; antineoplastic agent; durvalumab; epidermal growth factor receptor; monoclonal antibody; osimertinib; protein kinase inhibitor; adult; aged; arthralgia; Article; aspartate aminotransferase blood level; backache; clinical article; constipation; controlled study; coughing; decreased appetite; diarrhea; disease control; drug efficacy; drug safety; drug tolerability; dry skin; dyspnea; female; human; hypesthesia; interstitial lung disease; male; monotherapy; nausea; neutropenia; neutrophil count; non small cell lung cancer; overall survival; paronychia; phase 3 clinical trial; pneumonia; priority journal; productive cough; progression free survival; pruritus; rash; rhinorrhea; side effect; stomatitis; survival rate; treatment response; upper respiratory tract infection; viral upper respiratory tract infection; genetics; lung tumor; middle aged; non small cell lung cancer; pathology; randomized controlled trial; very elderly; Acrylamides; Adult; Aged; Aged, 80 and over; Aniline Compounds; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors
Publisher
Elsevier Inc
Type
journal article