D Miles1, J Gligorov2, F André3, D Cameron4, A Schneeweiss5, C Barrios6, B Xu7, A Wardley8, D Kaen9, L Andrade10, V Semiglazov11, M Reinisch12, S Patel13, M Patre14, L Morales14, S L Patel15, M Kaul13, T Barata16, J O'Shaughnessy17. 1. Mount Vernon Cancer Centre, Northwood, UK. Electronic address: David.miles@doctors.org.uk. 2. Medical Oncology Department, Institut Universitaire de Cancérologie Assistance Publique-Hôpitaux de Paris-Sorbonne Université, Paris, France. 3. Department of Medical Oncology, Gustave Roussy, Université Paris Sud, Villejuif, France. 4. University of Edinburgh, Edinburgh, UK. 5. Division of Gynecologic Oncology, National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany. 6. Latin American Cooperative Oncology Group, Porto Alegre RS, Brazil. 7. National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China. 8. National Institute for Health Research Manchester Clinical Research Facility at The Christie NHS Foundation Trust, Manchester, UK; Outreach Research & Innovation Group, Manchester, UK. 9. Centro Oncológico Riojano Integral and Universidad Nacional de La Rioja, La Rioja, Argentina. 10. Clinical Oncology, Santa Casa de Misericórdia da Bahia, Salvador, Brazil. 11. NN Petrov Research Institute of Oncology, St. Petersburg, Russia. 12. Kliniken Essen-Mitte, Essen, Germany. 13. Product Development Oncology, Genentech, Inc., South San Francisco, USA. 14. Global Product Development Medical Affairs Oncology, F. Hoffmann-La Roche Ltd, Basel, Switzerland. 15. Patient-Centered Outcomes Research, Genentech, Inc., South San Francisco, USA. 16. Pharma Development Biostatistics Oncology, F. Hoffmann-La Roche Ltd, Basel, Switzerland. 17. Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, USA.
Abstract
BACKGROUND: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. PATIENTS AND METHODS: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. RESULTS:Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. CONCLUSION: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.
RCT Entities:
BACKGROUND: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. PATIENTS AND METHODS: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. RESULTS: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. CONCLUSION: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.
Authors: Daniel J McGrail; Patrick G Pilié; Hui Dai; Truong Nguyen Anh Lam; Yulong Liang; Leonie Voorwerk; Marleen Kok; Xiang H-F Zhang; Jeffrey M Rosen; Amy B Heimberger; Christine B Peterson; Eric Jonasch; Shiaw-Yih Lin Journal: Sci Transl Med Date: 2021-10-27 Impact factor: 17.956
Authors: Leisha A Emens; Sylvia Adams; Ashley Cimino-Mathews; Mary L Disis; Margaret E Gatti-Mays; Alice Y Ho; Kevin Kalinsky; Heather L McArthur; Elizabeth A Mittendorf; Rita Nanda; David B Page; Hope S Rugo; Krista M Rubin; Hatem Soliman; Patricia A Spears; Sara M Tolaney; Jennifer K Litton Journal: J Immunother Cancer Date: 2021-08 Impact factor: 13.751
Authors: Elisabeth S Stovgaard; Karama Asleh; Nazia Riaz; Samuel Leung; Dongxia Gao; Lise B Nielsen; Anne-Vibeke Lænkholm; Eva Balslev; Maj-Britt Jensen; Dorte Nielsen; T O Nielsen Journal: Oncoimmunology Date: 2021-05-11 Impact factor: 8.110