Optimal chemotherapy in early TNBC is unclear. ADAPT TN demonstrated higher pCR (ypT0/is/ypN0/(primary endpoint): 46% vs. 29%) and better safety for nab-paclitaxel/carboplatin(nab-pac/carbo) vs nab-paclitaxel/gemcitabine (nab-pac/gem). Planned translational analysis (e.g. expression of 119 genes (nCounter®)) revealed a strong positive predictive impact of basal-like subtype, Ki‑67, HER2-score and immune markers (PDL1, PD1) on pCR.
Patients with centrally confirmed TNBC (ER/PR<1%, HER2-, cT1c-cT4c, cN0/+) were randomized to neoadjuvant 4x nab-pac/gem 125 mg/m2/1000 mg/m2 d1,8 q3w (A) vs. 4x nab-pac/carbo 125 mg/m2/ AUC2 day 1/8 3-weekly (q3w) (B). Adjuvant anthracycline-based chemotherapy CHT/4xEC was optional in patients with pCR at investigator decison. Per-protocol (interim) survival analysis was performed after 3y median follow-up (FU).
336 patients (median age 50y) were enrolled (48 centers, arms A/B: n=182/154). At baseline, 63% had cT2-4c tumors; 26.2% were cN+. Attainment of pCR was highly favorable for EFS (3y EFS: 92% vs. 71%, p<0.001) and OS (3y OS: 99.1% vs. 81.6%, p<0.001); 3y EFS was similar in Arm A vs. B (77.6% vs 80.8%, p=0.48); 3y OS was numerically higher in Arm B (84.7% vs. 92.2%, p=0.08).
Further (adjuvant) CHT was omitted in n=48 pCR patients (41%, n=26/22 A/B). Differences in EFS and OS by CHT were not significant (3y EFS: 97.0% with CHT vs. 85.5% without CHT, p=.16; 3y OS: 100% with CHT vs. 97.8 without CHT, p=.08).
Among immune/proliferation markers and clinical factors with significant (or borderline significant) association with pCR overall, only PD1 and clinical factors cN and cT were significantly associated with EFS in univariable analysis.
ADAPT TN confirms the strong prognostic impact of pCR in TNBC. However, the higher pCR rate favoring carbo was not reflected in a significant EFS or OS advantage for carbo-containing CHT in our collective after 36 months FU. Nonetheless, a more detailed evaluation of carbo-based de-escalated chemotherapy in selected patients could be a viable approach in TNBC.
Clinical trial identification