Inger Johanne Zwicky Eide1, Åslaug Helland2, Simon Ekman3, Anders Mellemgaard4, Karin Holmskov Hansen5, Saulius Cicenas6, Jussi Koivunen7, Bjørn Henning Grønberg8, Odd Terje Brustugun9. 1. Vestre Viken Hospital Trust, Drammen, Norway; Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: ingei@vestreviken.no. 2. Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Departement of Oncology, Oslo University Hospital, Oslo, Norway; University of Oslo, Department of Clinical Medicine, Oslo, Norway. 3. Thoracic Oncology Center, Karolinska University Hospital/Departement of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. 4. Herlev Hospital, Copenhagen, Denmark. 5. Odense University Hospital, Odense, Denmark. 6. National Cancer Institute, VU MF, Vilnius, Lithuania. 7. Oulu University Hospital, University of Oulu, MRC Oulu, Oulu, Finland. 8. Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. 9. Vestre Viken Hospital Trust, Drammen, Norway; Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Abstract
OBJECTIVES: In non-small cell lung cancer patients with acquired resistance to first- or second-generation EGFR-TKIs, osimertinib is approved in the presence of the T790 M resistance mutation. We assessed the efficacy of osimertinib in both T790M-positive and T790M-negative patients. MATERIALS AND METHODS: The TREM-study is an investigator-initiated, multi-centre, single-arm, phase 2 clinical trial conducted in five Northern European countries. Patients with progression on at least one previous EGFR-TKI were assigned to treatment with 80 mg of osimertinib daily until radiological progression or death. Patients were included regardless of the presence of T790 M. The primary endpoint was objective response rate (ORR). RESULTS: Of 199 included patients, 120 (60 %) were T790M-positive, 52 (26 %) were T790M-negative and 27 (14 %) had unknown T790M-status. 24 % had brain metastases and 15 % had an ECOG performance status of 2. Overall ORR was 48 % (95 % CI, 41 %-55 %), 60 % (51 %-69 %) for T790M-positive patients and 28 % (15 %-41 %) for T790M-negative patients, p < 0.001. ORR for patients with co-occurring del19 vs L858R was 61 % vs 32 %, p = 0.001. Duration of response was similar between the T790M-positive and -negative groups (11.8 vs 10.7 months, p = 0.229). Overall median progression-free survival (PFS) was 8.9 months (95 % CI, 7.4-10.5), and 10.8 vs 5.1 months for T790M-positive vs -negative patients (HR 0.62, p = 0.007). Median overall survival (OS) was 17.9 months (95 % CI, 14.4-21.3). For T790M-positive vs -negative median OS was 22.5 vs 13.4 months, (HR 0.55, p = 0.002). CONCLUSIONS: This study confirms the efficacy of osimertinib for T790M-positive patients. There was also clinically significant activity of osimertinib in a proportion of T790M-negative patients. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (NCT02504346).
OBJECTIVES: In non-small cell lung cancer patients with acquired resistance to first- or second-generation EGFR-TKIs, osimertinib is approved in the presence of the T790 M resistance mutation. We assessed the efficacy of osimertinib in both T790M-positive and T790M-negative patients. MATERIALS AND METHODS: The TREM-study is an investigator-initiated, multi-centre, single-arm, phase 2 clinical trial conducted in five Northern European countries. Patients with progression on at least one previous EGFR-TKI were assigned to treatment with 80 mg of osimertinib daily until radiological progression or death. Patients were included regardless of the presence of T790 M. The primary endpoint was objective response rate (ORR). RESULTS: Of 199 included patients, 120 (60 %) were T790M-positive, 52 (26 %) were T790M-negative and 27 (14 %) had unknown T790M-status. 24 % had brain metastases and 15 % had an ECOG performance status of 2. Overall ORR was 48 % (95 % CI, 41 %-55 %), 60 % (51 %-69 %) for T790M-positive patients and 28 % (15 %-41 %) for T790M-negative patients, p < 0.001. ORR for patients with co-occurring del19 vs L858R was 61 % vs 32 %, p = 0.001. Duration of response was similar between the T790M-positive and -negative groups (11.8 vs 10.7 months, p = 0.229). Overall median progression-free survival (PFS) was 8.9 months (95 % CI, 7.4-10.5), and 10.8 vs 5.1 months for T790M-positive vs -negative patients (HR 0.62, p = 0.007). Median overall survival (OS) was 17.9 months (95 % CI, 14.4-21.3). For T790M-positive vs -negative median OS was 22.5 vs 13.4 months, (HR 0.55, p = 0.002). CONCLUSIONS: This study confirms the efficacy of osimertinib for T790M-positive patients. There was also clinically significant activity of osimertinib in a proportion of T790M-negative patients. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (NCT02504346).
Authors: Dominika Kaźmierczak; Inger Johanne Zwicky Eide; Odd Terje Brustugun; Simon Ekman; Per Hydbring; Radosveta Gencheva; Yi Lai; Rolf Lewensohn; Georgios Tsakonas; Oscar Grundberg; Luigi de Petris; Marc McGowan Journal: Transl Lung Cancer Res Date: 2022-05
Authors: Mingjun Rui; Zijing Wang; Zhengyang Fei; Yao Wu; Yingcheng Wang; Lei Sun; Ye Shang; Hongchao Li Journal: Front Pharmacol Date: 2022-03-16 Impact factor: 5.810