LBA16 - IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer

Background

Based on findings from IMpassion130, international guidelines now recommend atezolizumab (A) + nab-paclitaxel (nP) for patients (pts) with locally advanced or metastatic TNBC (mTNBC) whose tumours express PD-L1 on tumour-infiltrating immune cells (IC). Here we report prespecified final OS and long-term safety results.

Methods

The study design and final PFS analysis have been reported (Schmid NEJM 2018). Pts were randomised 1:1 to A + nP or placebo (P) + nP. Co-primary endpoints were PFS (tested in parallel in ITT and PD-L1+ pts) and OS (tested hierarchically in ITT and, if significant, in PD-L1+ pts).

Results

As of 14 April 2020, 666/902 pts (73.8%) had died; median OS follow-up was 18.8 mo (IQR, 8.9-34.7 mo). 6% of pts in the A + nP arm and 2% in the P + nP arm remained on any treatment. OS data are in the Table. 460 A + nP arm pts and 430 P + nP arm pts were safety evaluable, of whom 8% and 3%, respectively, received nP for up to 24 mo. Similarly, 5% in the A + nP arm received nP for ≥ 24 mo (vs 1% in the P + nP arm). Respectively, 51% vs 43% had a G 3-4 AE; ≈ 1% per arm had a G 5 AE (no new G 5 AEs since last analysis; no patterns seen); 24% vs 19% had a serious AE, and 59% vs 42% had an AE of special interest (G 3-4 in 8% vs 5%). No confirmed or suspected COVID-19 AEs were reported. 19% in the A + nP arm and 8% in the P + nP arm had an AE leading to treatment discontinuation (most commonly due to neuropathy); in 18% and 8%, respectively, AEs led to nP discontinuation, and in 8% and 1%, AEs led to A or P discontinuation.

Conclusions

While OS differences for A + nP vs P + nP in the IMpassion130 ITT population were not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed in PD-L1+ pts (7.5-mo median OS improvement). A + nP remained safe and tolerable with longer follow-up. Results from this final and mature OS analysis are consistent with prior interim analyses. Table: LBA16

^a Stratification factors: prior taxane use, liver metastases, PD-L1 status. ^b Not significant ^c PD-L1 positivity defined as PD-L1–stained IC on ≥ 1% of the tumour area (VENTANA SP142 IHC assay) ^d Not formally tested per prespecified testing hierarchy.

Clinical trial identification

NCT02425891.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Ashley J. Pratt, PhD, of Health Interactions, and 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

L.A. Emens: Honoraria (self): AbbVie, Amgen, Celgene, Chugai, Gritstone, MedImmune, Peregrine, Shionogi, Syndax; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca, Bayer, MacroGenics, Replimune, Vaccinex; Travel/Accommodation/Expenses: Bristol Myers Squibb, Genentech/Roche, Novartis; Research grant/Funding (institution): Aduro Biotech, AstraZeneca, The Breast Cancer Research Foundation, Bristol Myers Squibb, Bolt Therapeutics, Corvus, The US Department of Defense, EMD Serono, Genentech, Maxcyte, Merck, The National Cancer Institute, The NSABP Foundation, Roche, The Transl; Licensing/Royalties: Aduro; Advisory/Consultancy: Roche. S. Adams: Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck, Amgen, BMS, Novartis, Celgene, Daiichi Sankyo. C.H. Barrios: Advisory/Consultancy: Boehringer- Ingelheim; Advisory/Consultancy: GSK; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/ Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Non-remunerated activity/ies: Bayer; Research grant/ Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Mylan; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Biomarin; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Abraxis BioScience; Research grant/Funding (institution): AB Science; Research grant/Funding (institution): Asana BioSciences; Research grant/Funding (institution): Exelixis, Research grant/Funding (institution): ImClone Systems, Research grant/Funding (institution): LEO Pharma; Research grant/Funding (institution): Millennium; Advisory/Consultancy: Merck Sharp and Dohme; Advisory/Consultancy: AstraZeneca. V.C. Dieras: Honoraria (self), Advisory/Consultancy: Roche/Genentech, Pfizer, Lilly, Novartis, Daiichi Sankyo, AstraZeneca, AbbVie, Seattle Genetics, Odonate, MSD. H. Iwata: Honoraria (self), Advisory/Consultancy: Chugai; Honoraria (self), Advisory/Consultancy: Novartis, AstraZeneca, Pfizer, Lilly, Daiichi-Sankyo, Eisai, Kyowa Kirin; Non-remunerated activity/ies: MSD, Bayer, BI, Nihon, Kayaku, Sanofi. S. Loi: Research grant/Funding (institution), Non-remunerated activity/ies: Novartis, BMS, Roche-Genentech, Merck; Research grant/Funding (institution): Puma, Eli Lilly, Pfizer; Unpaid consultant: Seattle Genetics; Unpaid consultant: Pfizer; Unpaid consultant: Novartis; Unpaid consultant: BMS; Unpaid consultant: AstraZeneca; Unpaid consultant: Roche/Genentech; Advisory/Consultancy (institution): Aduro Biotechnology. H.S. Rugo: Research grant/Funding (institution): Pfizer, Novartis, Lilly, Genentech/Roche, Merck, OBI, Eisai, Plexxikon, Immunomedics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Macrogeneics, Daiichi; Travel/Accommodation/Expenses: Puma, Mylan, Genentech/Roche, Novartis, Pfizer; Honoraria (self): Celltrion. A. Schneeweiss: Research grant/Funding (institution): Celgene, Roche, AbbVie, Molecular Partner; Advisory/Consultancy: Roche AstraZeneca; Travel/Accommodation/Expenses: Celgene, Roche, Pfizer; Honoraria (self): Roche, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly. E.P. Winer: Honoraria (self): Lilly, Genentech, Infinite MD, Carrick Therapeutics, GSK, Jounce, Genomic HEalth, Merck, Seattle Genetics; Honoraria (self), Leadership role: Leap. S. Patel: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. V. Henschel: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. A. Swat: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. M. Kaul: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. L. Molinero: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. S.Y. Chui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech/Roche. P. Schmid: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant, spouse -- consulting for Genentech: Roche; Honoraria (self): Medscape; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): GI Therapeutics; Honoraria (self): Health Interactions; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Merck; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bayer; Advisory/Consultancy: EISAI; Advisory/Consultancy: Celegence; Advisory/Consultancy: Puma; Research grant/Funding (institution), Spouse/Financial dependant, spouse -- consulting for Genentech: Genentech; Research grant/Funding (institution): Oncogenex.