Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer

P. Schmid, S. Adams, H. S. Rugo, A. Schneeweiss, C. H. Barrios, H. Iwata, V. Dieras, R. Hegg, S. A. Im, G. Shaw Wright, V. Henschel, L. Molinero, Stephen (Steve) Chui, R. Funke, A. Husain, E. P. Winer, S. Loi, L. A. Emens

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)- paclitaxel may enhance the anticancer activity of atezolizumab. METHODS In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression- free survival (in the intention-to-treat population and PD-L1-positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1-positive subgroup). RESULTS Each group included 451 patients (median follow-up, 12.9 months). In the intentionto- treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P = 0.002); among patients with PD-L1-positive tumors, the median progression- free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95% CI, 0.49 to 0.78; P<0.001). In the intention-to-treat analysis, the median overall survival was 21.3 months with atezolizumab plus nab-paclitaxel and 17.6 months with placebo plus nab-paclitaxel (hazard ratio for death, 0.84; 95% CI, 0.69 to 1.02; P = 0.08); among patients with PD-L1-positive tumors, the median overall survival was 25.0 months and 15.5 months, respectively (hazard ratio, 0.62; 95% CI, 0.45 to 0.86). No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9% of the patients who received atezolizumab plus nab-paclitaxel and in 8.2% of those who received placebo plus nab-paclitaxel. CONCLUSIONS Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1-positive subgroup. Adverse events were consistent with the known safety profiles of each agent.

Original languageEnglish (US)
Pages (from-to)2108-2121
Number of pages14
JournalNew England Journal of Medicine
Volume379
Issue number22
DOIs
StatePublished - Nov 29 2018
Externally publishedYes

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Triple Negative Breast Neoplasms
Nanoparticles
Ligands
Disease-Free Survival
Placebos
Confidence Intervals
Survival
Albumin-Bound Paclitaxel
MPDL3280A
Population
Intention to Treat Analysis
Poisons
Disease Progression
Neoplasms
Hormones

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Schmid, P., Adams, S., Rugo, H. S., Schneeweiss, A., Barrios, C. H., Iwata, H., ... Emens, L. A. (2018). Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. New England Journal of Medicine, 379(22), 2108-2121. https://doi.org/10.1056/NEJMoa1809615

Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. / Schmid, P.; Adams, S.; Rugo, H. S.; Schneeweiss, A.; Barrios, C. H.; Iwata, H.; Dieras, V.; Hegg, R.; Im, S. A.; Shaw Wright, G.; Henschel, V.; Molinero, L.; Chui, Stephen (Steve); Funke, R.; Husain, A.; Winer, E. P.; Loi, S.; Emens, L. A.

In: New England Journal of Medicine, Vol. 379, No. 22, 29.11.2018, p. 2108-2121.

Research output: Contribution to journalArticle

Schmid, P, Adams, S, Rugo, HS, Schneeweiss, A, Barrios, CH, Iwata, H, Dieras, V, Hegg, R, Im, SA, Shaw Wright, G, Henschel, V, Molinero, L, Chui, SS, Funke, R, Husain, A, Winer, EP, Loi, S & Emens, LA 2018, 'Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer', New England Journal of Medicine, vol. 379, no. 22, pp. 2108-2121. https://doi.org/10.1056/NEJMoa1809615
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. New England Journal of Medicine. 2018 Nov 29;379(22):2108-2121. https://doi.org/10.1056/NEJMoa1809615
Schmid, P. ; Adams, S. ; Rugo, H. S. ; Schneeweiss, A. ; Barrios, C. H. ; Iwata, H. ; Dieras, V. ; Hegg, R. ; Im, S. A. ; Shaw Wright, G. ; Henschel, V. ; Molinero, L. ; Chui, Stephen (Steve) ; Funke, R. ; Husain, A. ; Winer, E. P. ; Loi, S. ; Emens, L. A. / Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. In: New England Journal of Medicine. 2018 ; Vol. 379, No. 22. pp. 2108-2121.
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abstract = "BACKGROUND Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)- paclitaxel may enhance the anticancer activity of atezolizumab. METHODS In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression- free survival (in the intention-to-treat population and PD-L1-positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1-positive subgroup). RESULTS Each group included 451 patients (median follow-up, 12.9 months). In the intentionto- treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95{\%} confidence interval [CI], 0.69 to 0.92; P = 0.002); among patients with PD-L1-positive tumors, the median progression- free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95{\%} CI, 0.49 to 0.78; P<0.001). In the intention-to-treat analysis, the median overall survival was 21.3 months with atezolizumab plus nab-paclitaxel and 17.6 months with placebo plus nab-paclitaxel (hazard ratio for death, 0.84; 95{\%} CI, 0.69 to 1.02; P = 0.08); among patients with PD-L1-positive tumors, the median overall survival was 25.0 months and 15.5 months, respectively (hazard ratio, 0.62; 95{\%} CI, 0.45 to 0.86). No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9{\%} of the patients who received atezolizumab plus nab-paclitaxel and in 8.2{\%} of those who received placebo plus nab-paclitaxel. CONCLUSIONS Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1-positive subgroup. Adverse events were consistent with the known safety profiles of each agent.",
author = "P. Schmid and S. Adams and Rugo, {H. S.} and A. Schneeweiss and Barrios, {C. H.} and H. Iwata and V. Dieras and R. Hegg and Im, {S. A.} and {Shaw Wright}, G. and V. Henschel and L. Molinero and Chui, {Stephen (Steve)} and R. Funke and A. Husain and Winer, {E. P.} and S. Loi and Emens, {L. A.}",
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TY - JOUR

T1 - Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer

AU - Schmid, P.

AU - Adams, S.

AU - Rugo, H. S.

AU - Schneeweiss, A.

AU - Barrios, C. H.

AU - Iwata, H.

AU - Dieras, V.

AU - Hegg, R.

AU - Im, S. A.

AU - Shaw Wright, G.

AU - Henschel, V.

AU - Molinero, L.

AU - Chui, Stephen (Steve)

AU - Funke, R.

AU - Husain, A.

AU - Winer, E. P.

AU - Loi, S.

AU - Emens, L. A.

PY - 2018/11/29

Y1 - 2018/11/29

N2 - BACKGROUND Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)- paclitaxel may enhance the anticancer activity of atezolizumab. METHODS In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression- free survival (in the intention-to-treat population and PD-L1-positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1-positive subgroup). RESULTS Each group included 451 patients (median follow-up, 12.9 months). In the intentionto- treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P = 0.002); among patients with PD-L1-positive tumors, the median progression- free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95% CI, 0.49 to 0.78; P<0.001). In the intention-to-treat analysis, the median overall survival was 21.3 months with atezolizumab plus nab-paclitaxel and 17.6 months with placebo plus nab-paclitaxel (hazard ratio for death, 0.84; 95% CI, 0.69 to 1.02; P = 0.08); among patients with PD-L1-positive tumors, the median overall survival was 25.0 months and 15.5 months, respectively (hazard ratio, 0.62; 95% CI, 0.45 to 0.86). No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9% of the patients who received atezolizumab plus nab-paclitaxel and in 8.2% of those who received placebo plus nab-paclitaxel. CONCLUSIONS Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1-positive subgroup. Adverse events were consistent with the known safety profiles of each agent.

AB - BACKGROUND Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)- paclitaxel may enhance the anticancer activity of atezolizumab. METHODS In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression- free survival (in the intention-to-treat population and PD-L1-positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1-positive subgroup). RESULTS Each group included 451 patients (median follow-up, 12.9 months). In the intentionto- treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P = 0.002); among patients with PD-L1-positive tumors, the median progression- free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95% CI, 0.49 to 0.78; P<0.001). In the intention-to-treat analysis, the median overall survival was 21.3 months with atezolizumab plus nab-paclitaxel and 17.6 months with placebo plus nab-paclitaxel (hazard ratio for death, 0.84; 95% CI, 0.69 to 1.02; P = 0.08); among patients with PD-L1-positive tumors, the median overall survival was 25.0 months and 15.5 months, respectively (hazard ratio, 0.62; 95% CI, 0.45 to 0.86). No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9% of the patients who received atezolizumab plus nab-paclitaxel and in 8.2% of those who received placebo plus nab-paclitaxel. CONCLUSIONS Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1-positive subgroup. Adverse events were consistent with the known safety profiles of each agent.

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