Mansfield, A SKażarnowicz, AKaraseva, NSánchez, ADe Boer, RAndric, ZReck, MAtagi, SLee, J-SGarassino, MLiu, S VHorn, LWen, XQuach, CYu, WKabbinavar, FLam, SMorris, SCalifano, R2023-02-082023-02-082019-12-09http://hdl.handle.net/10668/14971The 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 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. 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. 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. NCT02763579.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/PD-L1TECENTRIQatezolizumabextensive-stage small-cell lung cancerquality of lifesafetyAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinEtoposideHumansLung NeoplasmsPatient Reported Outcome MeasuresQuality of Liferesearch article31959349open access10.1016/j.annonc.2019.10.0211569-8041http://www.annalsofoncology.org/article/S0923753419360788/pdf