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.
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).
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.
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. 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.
ITT population A + nP (n = 451) P + nP (n = 451) Events, n (%) 322 (71) 344 (76) Median OS (95% CI), mo 21.0 (19.0, 23.4) 18.7 (16.9, 20.8) OS HRa (95% CI); log-rank P 0.87 (0.75, 1.02); 0.0770b 3-year OS (95% CI), % 28 (24, 32) 25 (21, 29) (n = 185) (n = 184) Events, n (%) 120 (65) 139 (76) Median OS (95% CI), mo 25.4 (19.6, 30.7) 17.9 (13.6, 20.3) OS HRa (95% CI) 0.67 (0.53, 0.86)d 3-year OS (95% CI), % 36 (29, 43) 22 (16, 28)
NCT02425891.
Medical writing assistance for this abstract was provided by Ashley J. Pratt, PhD, CMPP of Health Interactions, Inc.
F. Hoffmann-La Roche, Ltd.
F. Hoffmann-La Roche, Ltd.
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.