Louis Fehrenbacher1, Joachim von Pawel2, Keunchil Park3, Achim Rittmeyer4, David R Gandara5, Santiago Ponce Aix6, Ji-Youn Han7, Shirish M Gadgeel8, Toyoaki Hida9, Diego L Cortinovis10, Manuel Cobo11, Dariusz M Kowalski12, Filippo De Marinis13, Mayank Gandhi14, Bradford Danner14, Christina Matheny14, Marcin Kowanetz14, Pei He14, Federico Felizzi14, Hina Patel14, Alan Sandler14, Marcus Ballinger14, Fabrice Barlesi15. 1. Kaiser Permanente Medical Center, Vallejo, California. Electronic address: louis.fehrenbacher@gmail.com. 2. Asklepios Fachkliniken München-Gauting, Gauting, Germany. 3. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 4. Pulmonary Clinic Immenhausen, Immenhausen, Germany. 5. University of California Davis Comprehensive Cancer Center, Sacramento, California. 6. University Hospital 12 de Octubre, Madrid, Spain. 7. National Cancer Center, Goyang, Republic of Korea. 8. University of Michigan, Ann Arbor, Michigan. 9. Aichi Cancer Center Hospital, Nagoya, Japan. 10. University Hospital San Gerardo, Monza, Italy. 11. Carlos Haya University Regional Málaga Hospital, Málaga, Spain. 12. The Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland. 13. European Institute of Oncology, Milan, Italy. 14. Genentech, Inc., South San Francisco, California. 15. Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Abstract
INTRODUCTION: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. METHODS: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m2, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1-expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. RESULTS:Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95% confidence interval: 0.64-0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95% confidence interval: 0.70-0.92, p = 0.0012) after minimum follow-up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death-ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment-related adverse events (14.9%) than did patients receiving docetaxel (42.4%); no grade 5 adverse events related to atezolizumab were observed. CONCLUSIONS: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up.
RCT Entities:
INTRODUCTION: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. METHODS:Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m2, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1-expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. RESULTS:Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95% confidence interval: 0.64-0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95% confidence interval: 0.70-0.92, p = 0.0012) after minimum follow-up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death-ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment-related adverse events (14.9%) than did patients receiving docetaxel (42.4%); no grade 5 adverse events related to atezolizumab were observed. CONCLUSIONS: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up.
Authors: M D Hellmann; T-W Kim; C B Lee; B-C Goh; W H Miller; D-Y Oh; R Jamal; C-E Chee; L Q M Chow; J F Gainor; J Desai; B J Solomon; M Das Thakur; B Pitcher; P Foster; G Hernandez; M J Wongchenko; E Cha; Y-J Bang; L L Siu; J Bendell Journal: Ann Oncol Date: 2019-07-01 Impact factor: 32.976
Authors: Yangyang Xu; Bing Wan; Xi Chen; Ping Zhan; Yuan Zhao; Tianli Zhang; Hongbing Liu; Muhammad Zubair Afzal; Said Dermime; Steven N Hochwald; Paul Hofman; Hossein Borghaei; Dang Lin; Tangfeng Lv; Yong Song Journal: Transl Lung Cancer Res Date: 2019-08
Authors: Bairavi Shankar; Jiajia Zhang; Abdul Rafeh Naqash; Patrick M Forde; Josephine L Feliciano; Kristen A Marrone; David S Ettinger; Christine L Hann; Julie R Brahmer; Biagio Ricciuti; Dwight Owen; Yukihiro Toi; Paul Walker; Gregory A Otterson; Sandip H Patel; Shunichi Sugawara; Jarushka Naidoo Journal: JAMA Oncol Date: 2020-12-01 Impact factor: 31.777