Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial

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 outcome...

Full description

Saved in:

Bibliographic Details
Published in:	Annals of oncology 2020-02, Vol.31 (2), p.310-317
Main Authors:	Mansfield, A.S., Każarnowicz, A., Karaseva, N., Sánchez, A., De Boer, R., Andric, Z., Reck, M., Atagi, S., Lee, J.-S., Garassino, M., Liu, S.V., Horn, L., Wen, X., Quach, C., Yu, W., Kabbinavar, F., Lam, S., Morris, S., Califano, R.
Format:	Article
Language:	eng
Subjects:	Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols - adverse effects atezolizumab Carboplatin - adverse effects Etoposide - therapeutic use extensive-stage small-cell lung cancer Humans Lung Neoplasms - drug therapy Patient Reported Outcome Measures PD-L1 Quality of Life safety TECENTRIQ
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 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. •First-line atezolizumab plus CP/ET had a similar safety profile to placebo plus CP/ET in both induction and maintenance.•The addition of atezolizumab did not adversely impact patient-reported health-related quality of life.•The risk:benefit ratio further suppo
ISSN:	0923-7534 1569-8041