TY - JOUR
T1 - Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer
AU - IMpassion131 investigators
AU - Miles, D.
AU - Gligorov, J.
AU - André, F.
AU - Cameron, D.
AU - Schneeweiss, A.
AU - Barrios, C.
AU - Xu, B.
AU - Wardley, A.
AU - Kaen, D.
AU - Andrade, L.
AU - Semiglazov, V.
AU - Reinisch, M.
AU - Patel, S.
AU - Patre, M.
AU - Morales, L.
AU - Patel, S. L.
AU - Kaul, M.
AU - Barata, T.
AU - O'Shaughnessy, J.
AU - Zhang, Q.
AU - Shao, Z.
AU - Wang, X.
AU - Geng, C.
AU - Yan, X.
AU - Tong, Z.
AU - Shen, K.
AU - Yin, Y.
AU - Sun, T.
AU - Yang, J.
AU - Feng, J.
AU - Yan, M.
AU - Wang, Y.
AU - Liu, Q.
AU - Zhang, S.
AU - De Laurentiis, M.
AU - Santoro, A.
AU - Guarneri, V.
AU - Colleoni, M.
AU - Natoli, C.
AU - Cortesi, L.
AU - Placido, S.
AU - Gianni, L.
AU - Ferrau, F.
AU - Livi, L.
AU - Zambelli, A.
AU - Del Mastro, L.
AU - Tonini, G.
AU - Montemurro, F.
AU - Bianchi, G.
AU - Yerushalmi, R.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - PD-L1
KW - advanced breast cancer
KW - atezolizumab
KW - immune checkpoint inhibitor
KW - paclitaxel
KW - triple-negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85111080655&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2021.05.801
DO - 10.1016/j.annonc.2021.05.801
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C2 - 34219000
AN - SCOPUS:85111080655
SN - 0923-7534
VL - 32
SP - 994
EP - 1004
JO - Annals of Oncology
JF - Annals of Oncology
IS - 8
ER -