[HTML][HTML] Overall survival (OS) in KATE2, a phase II study of programmed death ligand 1 (PD-L1) inhibitor atezolizumab (atezo)+ trastuzumab emtansine (T-DM1) vs …
Annals of Oncology, 2019•Elsevier
Background T-DM1 is indicated for the treatment of HER2+ metastatic BC previously treated
with trastuzumab and a taxane, separately or in combination. Atezo is an anti-PD-L1
antibody that inhibits PD-L1 binding to PD-1 and B7. 1 thereby restoring antitumor immunity.
In a phase 3 study, the addition of atezo to nab-paclitaxel significantly improved PFS in PD-
L1+ pts with metastatic triple negative BC. In KATE2 (NCT02924883), adding atezo to T-
DM1 in pts with HER2+ BC did not significantly increase PFS compared to T-DM1+ pbo in …
with trastuzumab and a taxane, separately or in combination. Atezo is an anti-PD-L1
antibody that inhibits PD-L1 binding to PD-1 and B7. 1 thereby restoring antitumor immunity.
In a phase 3 study, the addition of atezo to nab-paclitaxel significantly improved PFS in PD-
L1+ pts with metastatic triple negative BC. In KATE2 (NCT02924883), adding atezo to T-
DM1 in pts with HER2+ BC did not significantly increase PFS compared to T-DM1+ pbo in …
Background
T-DM1 is indicated for the treatment of HER2+ metastatic BC previously treated with trastuzumab and a taxane, separately or in combination. Atezo is an anti-PD-L1 antibody that inhibits PD-L1 binding to PD-1 and B7.1 thereby restoring antitumor immunity. In a phase 3 study, the addition of atezo to nab-paclitaxel significantly improved PFS in PD-L1+ pts with metastatic triple negative BC. In KATE2 (NCT02924883), adding atezo to T-DM1 in pts with HER2+ BC did not significantly increase PFS compared to T-DM1+pbo in the ITT population, but PFS was numerically longer in PD-L1+ pts. Here, we present OS and updated safety data from KATE2.
Methods
Pts with advanced HER2-positive BC that had progressed after treatment with trastuzumab and a taxane were randomized 2:1 to atezo 1200 mg or pbo, + T-DM1 3.6 mg/kg IV q3w. Pts were grouped by tumor infiltrating PD-L1+ immune cell (IC) status: IC0 vs IC1/2/3 (<1% vs ≥ 1%, respectively) using VENTANA SP142. The preplanned OS analysis in the ITT population was a secondary endpoint with 30% power to detect an effect. OS in PD-L1 subgroups was analyzed post-hoc.
Results
As of the cutoff date (11 Dec 2018), median follow-up was 19.5 mo in the atezo+T-DM1 arm and 18.2 mo in the pbo+T-DM1 arm. With 52 OS events reported, median OS was not reached in either arm. In the ITT population, 1-year OS was similar in both arms. In the PD-L1+ subgroup, 1-year OS was greater in the atezo+T-DM1 arm. The safety profile was consistent with the known safety profile of each drug. Grade ≥3 AEs (52.6% vs 44.8%) and serious AEs (36.1% vs 20.9%)—primarily pyrexia—were more frequent in the atezo+T-DM1 arm than in the T-DM1+pbo arm.
Conclusions
These data suggest a possible OS benefit with atezo+T-DM1 in PD-L1+ pts. However, given the small number of OS events, the short follow-up and lack of statistical power, further study is necessary.
Table. 305O
Empty CellITT PopulationPD-L1+ SubgroupPD-L1- Subgroup(IC 1/2/3)(IC 0)Empty CellAtezo +Pbo +Atezo +Pbo +Atezo +Pbo +T-DM1T-DM1T-DM1T-DM1T-DM1T-DM1(n = 133)(n = 69)(n = 57)(n = 27)(n = 76)(n = 42)Pts with OS event, n (%)32201182112(24.1%)(29.0%)(19.3%)(29.6%)(27.6%)(28.6%)Median OSNENENENENENEStratified HR (95% CI)0.740.550.88(0.42–1.30)(0.22–1.38)(0.43–1.80)1-year survival rate89.1%89.0%94.3%87.9%85.1%89.7%
CI, confidence interval; HR, hazard ratio; IC, immune cell infiltrate staining of PD-L1; NE, not estimable; OS, overall survival.
Clinical trial identification
NCT02924883.
Editorial acknowledgement
Medical writing assistance was provided by Katherine Stevens-Favorite, PhD and Holly Strausbaugh, PhD of Twist Medical LCC and funded by F. Hoffmann-La Roche.
Legal entity responsible for the study
F. Hoffmann - La Roche.
Funding
F. Hoffmann - La Roche.
Disclosure
L.A. Emens: Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol Meyers Squibb; Honoraria (self), Advisory / Consultancy: Celgene; Advisory / Consultancy: eTHeRNA; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Gristone; Honoraria (self), Advisory / Consultancy: Medimmune; Advisory / Consultancy: Molecuvax; Honoraria (self), Advisory / Consultancy, Travel / Accommodation …
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