J von Pawel1, R Bordoni2, M Satouchi3, L Fehrenbacher4, M Cobo5, J Y Han6, T Hida7, D Moro-Sibilot8, P Conkling9, D R Gandara10, A Rittmeyer11, M Gandhi12, W Yu12, C Matheny12, H Patel12, A Sandler12, M Ballinger12, M Kowanetz12, K Park13. 1. Asklepios Fachkliniken München-Gauting, Gauting, Germany. Electronic address: j.pawel@asklepios.com. 2. Georgia Cancer Specialists and Northside Hospital Cancer Institute, Atlanta, GA, USA. 3. Hyogo Cancer Center, Akashi, Japan. 4. Kaiser Permanente Medical Center, Vallejo, CA, USA. 5. Hospital Regional Universitario Málaga, IBIMA, Málaga, Spain. 6. National Cancer Center, Goyang, South Korea. 7. Aichi Cancer Center Hospital, Nagoya, Japan. 8. CHU Grenoble-Alpes, Grenoble Albert Michallon, La Tronche, France. 9. US Oncology Research, Virginia Oncology Associates, Norfolk, VA, USA. 10. UC Davis Comprehensive Cancer Center, Sacramento, CA, USA. 11. Lungenfachklinik Immenhausen, Immenhausen, Germany. 12. Genentech, Inc., South San Francisco, CA, USA. 13. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Abstract
BACKGROUND:Atezolizumab (anti-programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non-small-cell lung cancer based on OAK-a randomised, phase III trial that showed significantly improved survival with atezolizumab versus docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs). METHODS: In OAK (NCT02008227), patients were randomised 1:1 to receive atezolizumab or docetaxel until loss of clinical benefit or disease progression, respectively. Overall survival was evaluated after a 26-month minimum follow-up, including in patient subgroups defined by best overall response (BOR). LTSs were defined as patients who lived ≥24 months since randomisation. Non-LTSs died within 24 months, and patients censored before 24 months were excluded from the analysis. The baseline characteristics, including biomarkers, BOR, subsequent non-protocol therapy (NPT) and safety, are reported. RESULTS:Survival benefit with atezolizumab was observed across all patient subgroups defined by BOR. More atezolizumab-treated patients were LTSs versus those treated with docetaxel (28% versus 18%). Most atezolizumab responders were LTSs (77%) versus only 48% of docetaxel responders. However, 21% of atezolizumab-arm LTSs had progressive disease (PD) as BOR, and more atezolizumab-arm LTSs than non-LTSs continued treatment post-PD. Fifty-two percent of docetaxel-arm LTSs received immunotherapy as subsequent NPT. Despite extended treatment duration in atezolizumab-arm LTSs (median, 18 months), atezolizumab was well tolerated. CONCLUSIONS: After >2 years of follow-up, atezolizumab continued to provide durable survival benefit versus docetaxel, with tolerable safety. Atezolizumab-arm LTSs were enriched for patients with high PD-L1 expression and included PD-L1-negative patients. Long-term survival was not limited to responders.
RCT Entities:
BACKGROUND:Atezolizumab (anti-programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non-small-cell lung cancer based on OAK-a randomised, phase III trial that showed significantly improved survival with atezolizumab versus docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs). METHODS: In OAK (NCT02008227), patients were randomised 1:1 to receive atezolizumab or docetaxel until loss of clinical benefit or disease progression, respectively. Overall survival was evaluated after a 26-month minimum follow-up, including in patient subgroups defined by best overall response (BOR). LTSs were defined as patients who lived ≥24 months since randomisation. Non-LTSs died within 24 months, and patients censored before 24 months were excluded from the analysis. The baseline characteristics, including biomarkers, BOR, subsequent non-protocol therapy (NPT) and safety, are reported. RESULTS: Survival benefit with atezolizumab was observed across all patient subgroups defined by BOR. More atezolizumab-treated patients were LTSs versus those treated with docetaxel (28% versus 18%). Most atezolizumab responders were LTSs (77%) versus only 48% of docetaxel responders. However, 21% of atezolizumab-arm LTSs had progressive disease (PD) as BOR, and more atezolizumab-arm LTSs than non-LTSs continued treatment post-PD. Fifty-two percent of docetaxel-arm LTSs received immunotherapy as subsequent NPT. Despite extended treatment duration in atezolizumab-arm LTSs (median, 18 months), atezolizumab was well tolerated. CONCLUSIONS: After >2 years of follow-up, atezolizumab continued to provide durable survival benefit versus docetaxel, with tolerable safety. Atezolizumab-arm LTSs were enriched for patients with high PD-L1 expression and included PD-L1-negative patients. Long-term survival was not limited to responders.
Authors: Thomas P Brouwer; Natasja L de Vries; Tamim Abdelaal; Ricki T Krog; Zheng Li; Dina Ruano; Arantza Fariña; Boudewijn P F Lelieveldt; Hans Morreau; Bert A Bonsing; Alexander L Vahrmeijer; Frits Koning; Noel F C C de Miranda Journal: J Immunother Cancer Date: 2022-07 Impact factor: 12.469