LBA15 - Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC)

Background

In the phase 3 IMpassion130 trial, combining atezo with first-line nab-paclitaxel for mTNBC showed significantly improved progression-free survival (PFS) and clinically meaningful overall survival (OS) benefit in patients with PD-L1+ mTNBC [Schmid NEJM 2018]. IMpassion131 (NCT03125902) evaluated atezo + PAC as first-line treatment for mTNBC.

Methods

Eligible patients (no prior systemic therapy or ≥12 months since [neo]adjuvant chemotherapy) were randomised 2:1 to atezo 840 mg or placebo (d 1 & 15 q28d), both with PAC 90 mg/m² (d 1, 8 & 15 q28d) until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status (immune cell [IC] expression <1% vs ≥1% by VENTANA SP142 assay), prior taxane, liver metastases and geographic region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1+ (IC ≥1%) population, then in the intent-to-treat (ITT) population. OS and overall response rate (ORR) were secondary endpoints.

Results

Of 651 randomised patients, 45% had PD-L1+ mTNBC, 48% were taxane pretreated, 31% had de novo mTNBC and 27% liver metastases. Adding atezo to PAC did not improve PFS or OS in either the PD-L1+ or ITT populations (Table). PFS results in subgroups were consistent with primary results. PAC exposure was not compromised by the addition of atezo. Grade 5 (2% placebo vs 2% atezo) and grade 3/4 AEs (43% vs 49%) were balanced between arms and the safety profile was consistent with known risks of each study drug. Table: LBA15

^aUnconfirmed

Conclusions

Atezo + PAC did not improve PFS or OS vs placebo + PAC. No new safety signals were seen. Potential reasons for the contrast with the benefit seen in IMpassion130 (atezo + nab-paclitaxel) need further exploration.

Clinical trial identification

NCT03125902.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd), funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

D.W. Miles: Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genomic Health. J. Gligorov: Advisory/Consultancy, Research grant/Funding (institution): Daichi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genomic Health; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: MSD; Advisory/Consultancy: Mylan; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Onxeo; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Research grant/Funding (institution): Immunomedics. F. André: Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Lilly; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: GlaxoSmithKline. D. Cameron: Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: AstraZeneca. A. Schneeweiss: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Molecular Partner; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly. C.H. Barrios: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Research grant/Funding (institution): PharmaMar; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. B. Xu: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Daiichi-Sankyo. A.M. Wardley: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi-Sankyo; Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Athenex; Honoraria (self), Advisory/Consultancy: Gerson Lehrman Group; Honoraria (self), Advisory/Consultancy: Guidepoint Global; Honoraria (self): Coleman Expert Network; Honoraria (self): Helios; Honoraria (self): Health Care America; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Advisory/Consultancy: NAPP Pharma; Advisory/Consultancy, Research grant/Funding (institution): Accord Research; Advisory/Consultancy: Coleman Research; Leadership role, Full/Part-time employment, Medical Director: NIHR Manchester Clinical Research Facility at The Christie; Leadership role, Strategy Director: Association of Cancer Physicians; Leadership role, Committee Member: UK Breast Cancer Group; Leadership role, Committee Member: NHS England Chemotherapy Clinical Reference Group; Leadership role, Faculty: ESMO Breast cancer; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): 1G1 Therapeutics; Shareholder/Stockholder/Stock options, Officer/Board of Directors, Spouse/Financial dependant: Andrew Wardley Limited; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Manchester Cancer Academy; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Outreach Research & Innovation Group Limited; Speaker Bureau/Expert testimony: Eisai; Research grant/Funding (self): NIHR. D. Kaen: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Raffo-Tecnofarma; Honoraria (self), Advisory/Consultancy: Varifarma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Lilly Oncology; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Array BioPharma Inc. L. Andrade: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Zodiac Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Janssen-Cilag; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche/Genentech; Speaker Bureau/Expert testimony: Merck Sharp Dohme; Speaker Bureau/Expert testimony: Novartis; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Regeneron. M. Reinisch: Honoraria (self), Advisory/Consultancy: Roche Pharma AG; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Hexal; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Celgene. M. Patre: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. L. Morales: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. K. Russell: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. M. Donica: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. J. O’Shaughnessy: Honoraria (self), Advisory/Consultancy: AbbVie Inc.; Honoraria (self), Advisory/Consultancy: Agendia; Honoraria (self), Advisory/Consultancy: Amgen Biotechnology; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Celgene Corporation; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GRAIL; Honoraria (self), Advisory/Consultancy: Immunomedics; Honoraria (self), Advisory/Consultancy: Heron Therapeutics; Honoraria (self), Advisory/Consultancy: Ipsen Biopharmaceuticals; Honoraria (self), Advisory/Consultancy: Jounce Therapeutics; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Myriad; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Ondonate Therapeutics; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Advisory/Consultancy: Prime Oncology; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Syndax Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Takeda. All other authors have declared no conflicts of interest.