49MO - 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: 49MO

Final OS analysis

^a Stratified by: 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 P value not shown since PD-L1+ OS not formally tested per hierarchical study design.

Clinical trial identification

NCT02425891.

Editorial acknowledgement

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

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

H. Iwata: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, uncompensated IMpassion130 study steering committee member, editorial support: Roche; Non-remunerated activity/ies, editorial support: Chugai; Honoraria (self), Advisory/Consultancy: Novartis; AstraZeneca; Pfizer; Eli Lilly; Daiichi Sankyo. L. Emens: Honoraria (self): AbbVie; Amgen; Celgene; Chugai; Gritstone; MedImmune; Peregrine; Shionogi; Syndax; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Bayer; MacroGenics; Replimune; Vaccinex; Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution), Travel/Accommodation/Expenses, Non-remunerated activity/ies, editorial support, uncompensated IMpassion130 study and KATE2 study steering committee chairs: Genentech/Roche; Shareholder/Stockholder/Stock options, Potential for stock in future: Molecuvax; Research grant/Funding (institution), Licensing/Royalties: Aduro Biotech; Research grant/Funding (institution): Breast Cancer Research Foundation; Research grant/Funding (institution): Bolt Therapeutics, Corvus, US Dept of Defense, EMD Serono, Maxcyte, Merck, National Cancer Institute, NSABP Foundation, Translational Breast Cancer Research Consortium, Tempest, HeritX. S. Adams: Advisory/Consultancy, Research grant/Funding (institution), uncompensated advisory/consulting: BMS; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, uncompensated advisory/consulting, editorial support: Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution), uncompensated advisory/consulting: Merck; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Novartis. C.H. Barrios: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Novartis; Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Boehringer Ingelheim; GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution), editorial support: Roche/Genentech; Research grant/Funding (institution): Eli Lily; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Mylan; Research grant/Funding (institution): Merrimack; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Astellas, BioMarin; Advisory/Consultancy: Eisai, Bayer; Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Merck Sharp and Dohme; Research grant/Funding (institution): Abraxis BioScience, AB Science, Asana BioSciences, Medivation, Exelexis, ImClone Systems, LEO Pharma, Millennium. V. Diéras: Advisory/Consultancy, editorial support: Roche/Genentech; Advisory/Consultancy: Pfizer; Eli Lilly; Novartis; Daiichi Sankyo; AstraZeneca; AbbVie; MSD; Seattle Genetics; Odonate. S. Loi: Advisory/Consultancy, Research grant/Funding (institution), Unpaid consultant: Novartis; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution), Unpaid consultant: Merck; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, Unpaid consultant, editorial support: Roche/Genentech; Research grant/Funding (institution): Puma; Advisory/Consultancy, Research grant/Funding (institution), Unpaid consultant: Pfizer; Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Unpaid consultant: Seattle Genetics; Advisory/Consultancy, Unpaid consultant: AstraZeneca; Advisory/Consultancy, Consulting fees paid to institution: Aduro Biotech. H.S. Rugo: Research grant/Funding (institution), Travel/Accommodation/Expenses, Non-remunerated activity/ies, editorial support: Roche/Genentech; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Merck; Research grant/Funding (institution): OBI; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Plexxikon; Travel/Accommodation/Expenses: MacroGenics; Travel/Accommodation/Expenses: Puma; Travel/Accommodation/Expenses: Mylan; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self): Celltrion. A. Schneeweiss: Honoraria (self), Research grant/Funding (institution): Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Non-remunerated activity/ies, editorial support: Roche; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Molecular Partners; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Merck Sharp and Dohme; Honoraria (self): Tesaro; Honoraria (self): Eli Lilly; Honoraria (self), Travel/Accommodation/Expenses: Pfizer. E.P. Winer: Honoraria (self): Eli Lilly; Honoraria (self), Advisory/Consultancy: Leap; Honoraria (self): Genentech; Honoraria (self): Infinite MD; Honoraria (self): Carrick Therapeutics; Honoraria (self): GlaxoSmithKline; Honoraria (self): Jounce; Honoraria (self): Genomic Health; Honoraria (self): Merck; Honoraria (self): Seattle Genetics; Non-remunerated activity/ies, editorial support: Roche. S. Patel: Full/Part-time employment, Non-remunerated activity/ies, editorial support: Roche/Genentech. V. Henschel: Shareholder/Stockholder/Stock options, Full/Part-time employment, Non-remunerated activity/ies, editorial support: Roche. A. Swat: Full/Part-time employment, Non-remunerated activity/ies, editorial support: Roche. M. Kaul: Full/Part-time employment, Non-remunerated activity/ies, editorial support: Roche/Genentech. L. Molinero: Shareholder/Stockholder/Stock options, Full/Part-time employment, Non-remunerated activity/ies, Use patent to disclose with Roche/Genentech, editorial support: Roche/Genentech. S.S. Chui: Shareholder/Stockholder/Stock options, Full/Part-time employment, Non-remunerated activity/ies, Use patent to disclose with Roche/Genentech, editorial support: Roche/Genentech. P. Schmid: Research grant/Funding (institution), Spouse/Financial dependant: Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant, Non-remunerated activity/ies, editorial support, uncompensated steering committee member: F. Hoffmann-La Roche; Honoraria (self): Medscape; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Merck; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Celgene; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Puma; Honoraria (self): GI Therapeutics; Research grant/Funding (institution): OncoGenex.