James Chih-Hsin Yang1, Frances A Shepherd2, Dong-Wan Kim3, Gyeong-Won Lee4, Jong Seok Lee5, Gee-Chen Chang6, Sung Sook Lee7, Yu-Feng Wei8, Yun Gyoo Lee9, Gianluca Laus10, Barbara Collins10, Francesca Pisetzky11, Leora Horn12. 1. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China. Electronic address: chihyang@ntu.edu.tw. 2. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Ontario, Canada. 3. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 4. Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea. 5. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea. 6. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Republic of China. 7. Hematology-Oncology, Inje University College of Medicine, Busan, Republic of Korea. 8. Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, Republic of China. 9. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 10. AstraZeneca, Cambridge, United Kingdom. 11. AstraZeneca, Den Haag, The Netherlands. 12. Thoracic Oncology Program, Vanderbilt University Medical Center, Nashville, Tennessee.
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.
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.
Authors: Jan P Bogen; Stefania C Carrara; David Fiebig; Julius Grzeschik; Björn Hock; Harald Kolmar Journal: Front Immunol Date: 2021-05-10 Impact factor: 7.561