IMpassion130: Results from a global, randomised, double-blind, phase III study of atezolizumab (atezo) plus nab-paclitaxel (nab-P) vs placebo plus nab-P in treatment-naive, locally advanced or metastatic triple-negative breast cancer (mTNBC)

Background: mTNBC is the breast cancer subtype with worst prognosis and is typically treated with chemo. Atezo (anti–PD-L1) combined with nab-P (A+nab-P) demonstrated safety and clinical activity in mTNBC (Pohlmann AACR 2018). Here we report final PFS and initial interim OS results from IMpassion130, a ph 3, double-blind, randomised study evaluating 1L A+nab-P in mTNBC Methods: Eligible patients (pts) with histologically documented mTNBC, ECOG PS 0-1 and tumour tissue for PD-L1 testing were randomised 1:1 to IV atezo 840 mg or placebo (P) on d1 and 15 (q2w) + nab-P 100 mg/m2 on d1, 8 and 15 of a 28-d cycle until progression. Stratification factors were prior taxanes, liver mets and tumour PD-L1 status on immune cells (positive: ≥1%). Co-primary endpoints (EPs) were PFS (ITT and PD-L1+ pts) and OS (ITT and, if significant, PD-L1+ pts). Key secondary EPs were ORR and DOR. Results: At data cutoff 17 Apr 2018, median follow-up was 12.9 mo. In the A+nab-P and P+nab-P arms, respectively (n = 451 each), median age was 55 and 56 y; 57% and 60% had ECOG PS 0 and 63% each had prior (neo)adjuvant treatment. Efficacy data are in the table. All-cause AEs occurred in 99% (G3-4, 49%) and 98% (G3-4, 42%) of evaluable pts in the A+nab-P and P+nab-P arms (n = 452, 438), respectively. Nausea, cough, neutropenia, pyrexia and hypothyroidism were ≥5% higher with A+nab-P. 3/6 G5 AEs in A+nab-P and 1/3 in P+nab-P pts were related to either atezo, P or nab-P. G3-4 AEs of special interest occurred in 8% of A+nab-P and 4% of P+nab-P pts. Conclusions: IMpassion130 met its co-primary PFS EP in ITT and PD-L1+ pts, with clinically meaningful OS benefit seen at interim OS analysis in PD-L1+ pts. A+nab-P was well tolerated, with a safety profile consistent with each agent. This first positive ph 3 mTNBC immunotherapy study highlights A+nab-P as a new therapy for untreated PD-L1+ pts.Table: LBA1_PRIMpassion130aNCT02425891. efficacy resultsITT populationPD-L1+ subpopulationbPD-L1 positivity was defined per the VENTANA SP142 IHC assay as PD-L1 expression on tumour-infiltrating immune cells ≥ 1%.A+nab-P (n = 451)P+nab-P (n = 451)A+nab-P (n = 185)P+nab-P (n = 184)Co-primary endpointscPFS, ORR and DOR evaluated per investigator-assessed Response Evaluation Criteria in Solid Tumors v1.1.Median PFS (95% CI), mo7.2 (5.6, 7.5)5.5 (5.3, 5.6)7.5 (6.7, 9.2)5.0 (3.8, 5.6)PFS HR (95% CI; P value)0.80 (0.69, 0.92; P = 0.0025)0.62 (0.49, 0.78); P < 0.0001Median OS (95% CI), mo21.3 (17.3, 23.4)17.6 (15.9, 20.0)25.0 (22.6, NE)15.5 (13.1, 19.4)OS HR (95% CI; P value)0.84 (0.69, 1.02; P = 0.0840)0.62 (0.45, 0.86); P = 0.0035dNot formally tested due to hierarchical study design.Secondary endpointscPFS, ORR and DOR evaluated per investigator-assessed Response Evaluation Criteria in Solid Tumors v1.1.ORR-evaluable pts, n450449185183ORR (95% CI), %56 (51, 61)46 (41, 51)59 (51, 66)43 (35, 50)Difference in ORR (95% CI), %; P value (Cochran-Mantel-Haenszel)10 (3, 17); P = 0.002116 (6, 27); P = 0.0016DOR-evaluable pts, n25220610978Median DOR (95% CI), mo7.4 (6.9, 9.0)5.6 (5.5, 6.9)8.5 (7.3, 9.7)5.5 (3.7, 7.1)OS results based on initial interim OS analysis. DOR, duration of response; HR, hazard ratio; ITT, intent-to-treat; NE, not estimable; ORR, objective response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival.a NCT02425891.b PD-L1 positivity was defined per the VENTANA SP142 IHC assay as PD-L1 expression on tumour-infiltrating immune cells ≥ 1%.c PFS, ORR and DOR evaluated per investigator-assessed Response Evaluation Criteria in Solid Tumors v1.1.d Not formally tested due to hierarchical study design. Open table in a new tab OS results based on initial interim OS analysis. DOR, duration of response; HR, hazard ratio; ITT, intent-to-treat; NE, not estimable; ORR, objective response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival. Clinical trial identification: NCT02425891. Editorial acknowledgement: Medical writing support provided by Ashley J. Pratt, PhD, CMPP, of Health Interactions. Legal entity responsible for the study: F. Hoffmann-La Roche AG. Funding: F. Hoffmann-La Roche AG. Disclosure: P. Schmid: Honoraria: AstraZeneca, Bayer, Boehringer, Celgene, Eisai, Novartis, Pfizer, Puma, Roche/Genentech; Grants or support/contracted research: Astellas, AstraZeneca, Medivation, Novartis, Oncogenex, Roche/Genentech (all paid to institution); Wife: Employee: Roche. S. Adams: Research funding for this trial to institution. H.S. Rugo: Grants: Pfizer, Novartis, Lilly, Genentech/Roche, Macrogenics; Other: Puma, Mylan, Genentech/Roche; Grants: Merck, OBI, Eisai, Plexxikon; Other: Novartis, Pfizer, outside the submitted work. A. Schneeweiss: Honoraria: Roche, Celgene, AstraZeneca, Pfizer, Novartis. C.H. Barrios: Honoraria: Novartis, Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, Eisai. Consulting or advisory role: Boehringer Ingelheim, Roche/Genentech, Novartis, GlaxoSmithKline, Eisai, Pfizer; Research funding: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas, Biomarin, Bristol-Myers Squibb, Daiichi Sankyo, Abraxis Bioscience, AB Science, Asana Biosciences, Medivation, Exelixis, ImClone Systems, LEO Pharma, Millennium. H. Iwata: Grants and personal fees: Daiichi Sankyo, during the conduct of the study; Grants and personal fees: Chugai, AstraZeneca, Pfizer; Personal fees: Eisai, Grants: MSD, Kyowahakou Kirin, GSK, Lilly, Novartis, Bayer, outside the submitted work. V. Dieras: Travel expenses: Roche, Novartis, Pfizer, GSK, Eisai, AstraZeneca. Honoraria for consultant: Roche/Genentech, Novartis, Lilly, Pfizer, Eisai, Nektar, Astellas, AbbVie, MSD, Tesaro, Daiichi Sankyo, Odonate; Honoraria for speaker: Roche, Novartis, Eisai, Pfizer, Lilly. S-A. Im: Research grant: AstraZeneca, outside the submitted work; Advisory board member: AstraZeneca, Hanmi, Novartis, Roche, Pfizer for the last 5 years. V. Henschel: Employee and stockholder: Roche. L. Molinero, A. Husain: Employee and stock owner: Roche. S.Y. Chui: Employee: Genentech; Stock owner: Roche. R. Funke: Roche employee and stock owner. E.P. Winer: Honoraria for consulting: Genentech/Roche; Other honoraria: Lilly, Tessaro, Leap. S. Loi: Research funding to institution: Novartis, Bristol Meyers Squibb, Merck, Roche-Genentech, Puma Biotechnology, Pfizer. L.A. Emens: Employment: Johns Hopkins University and FDA-CTGTAC; Board of Directors for Society for Immunotherapy of Cancer (SITC); Honoraria for consultant/on an advisory board: AbbVie, Amgen, Astrazeneca, Bayer, Bristol Meyers Squibb, Celgene, eTHeRNA, Gritstone, Medimmune, Molecuvax, Peregrine, Replimune, Syndax, Vaccinex; Research funding: Aduro Biotech, Atrazeneca, Corvus, EMD Serono, Genentech, HeritX, Inc., Roche; Royalties: Aduro IND Licensing/vaccine (<25K). All other authors have declared no conflicts of interest.