A S Mansfield1, A Każarnowicz2, N Karaseva3, A Sánchez4, R De Boer5, Z Andric6, M Reck7, S Atagi8, J-S Lee9, M Garassino10, S V Liu11, L Horn12, X Wen13, C Quach13, W Yu14, F Kabbinavar13, S Lam13, S Morris15, R Califano16. 1. Division of Medical Oncology, Mayo Clinic, Rochester, USA. Electronic address: Mansfield.Aaron@mayo.edu. 2. Department of Oncology, Tuberculosis and Lung Disease Hospital, Olsztyn, Poland. 3. City Clinical Oncology Dispensary, St Petersburg, Russia. 4. Department of Medical Oncology, Hospital Universitario "Virgen del Rocio", Seville, Spain. 5. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 6. Department of Medical Oncology, University Hospital Medical Center Bezanijska Kosa, Belgrade, Serbia. 7. Department of Thoracic Oncology, German Center for Lung Research (DZL), Großhansdorf, Germany. 8. Department of Thoracic Oncology, Kinki-Chuo Chest Medical Center, Osaka, Japan. 9. Division of Hematology-Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. 10. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 11. Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA. 12. Thoracic Oncology Program, Vanderbilt University Medical Center, Nashville, USA. 13. Product Development Oncology, Genentech, Inc., South San Francisco, USA. 14. Biometrics, Genentech, Inc., South San Francisco, USA. 15. Global PD Medical Affairs (Oncology), F. Hoffmann-La Roche Ltd, Basel, Switzerland. 16. Department of Medical Oncology, The Christie NHS Foundation Trust, and Division of Cancer Sciences, University of Manchester, Manchester, UK.
Abstract
BACKGROUND: The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen. PATIENTS AND METHODS: Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-LC13. RESULTS: Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3-4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm. CONCLUSIONS: In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting. CLINICAL TRIALS NUMBER: NCT02763579.
BACKGROUND: The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen. PATIENTS AND METHODS: Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-LC13. RESULTS: Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3-4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm. CONCLUSIONS: In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting. CLINICAL TRIALS NUMBER: NCT02763579.
Authors: Barbara Melosky; Parneet K Cheema; Anthony Brade; Deanna McLeod; Geoffrey Liu; Paul Wheatley Price; Kevin Jao; Devin D Schellenberg; Rosalyn Juergens; Natasha Leighl; Quincy Chu Journal: Oncologist Date: 2020-09-23
Authors: Daphne W Dumoulin; Anne-Marie C Dingemans; Joachim G J V Aerts; Jordi Remon; Dirk K M De Ruysscher; Lizza E L Hendriks Journal: Transl Lung Cancer Res Date: 2021-06
Authors: Neal M Dixit; Katie P Truong; Soniya V Rabadia; David Li; Pratyaksh K Srivastava; Tina Mosaferi; Marcella A Calfon Press; Ines Donangelo; Theodoros Kelesidis Journal: J Endocr Soc Date: 2020-08-28