Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab-Paclitaxel+Gemcitabine in Triple-Negative Breast Cancer: Randomized WSG-ADAPT-TN Trial Results

Gluz, Oleg; Nitz, Ulrike; Liedtke, Cornelia; Christgen, Matthias; Grischke, Eva‐Maria; Forstbauer, Helmut; Braun, Michael; Warm, Mathias; Hackmann, John; Uleer, Christoph; Aktas, Bahriye; Schumacher, Claudia; Bangemann, Nikola; Lindner, Christoph; Küemmel, Sherko; Clemens, Michael; Potenberg, Jochem; Staib, Peter; Kohls, A.; Schumann, Raquel von; Kates, Ronald; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans; Harbeck, Nadia

doi:10.1093/jnci/djx258

Cited by 102 publications

(101 citation statements)

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“…Table summarizes baseline distributions of clinical variables. Baseline characteristics were balanced between the trial arms . There were 182 patients in the nab‐pac/gem arm (A) and 154 in the nab‐pac/carbo arm (B).…”

Section: Resultsmentioning

confidence: 99%

“…Baseline characteristics were balanced between the trial arms. 37 There were 182 patients in the nab-pac/gem arm (A) and 154 in the nab-pac/carbo arm (B). As previously reported, pCR occurred in 36% of patients overall; A: 28.4%, B: 44.5% (p = 0.004).…”

Section: Resultsmentioning

confidence: 99%

“…Early TNBC patients with cT1c-cT4c or clinically node positive tumors entered the WSG-ADAPT-TN trial (ClinicalTrials.gov [NCT01815242]), as previously reported. 37 TN status was centrally confirmed according to the following criteria: ER and PR positivity both <1%, HER2 negativity (Score 0 or 1+ or in case of score 2+ negative FISH test). The trial compared two 12-week neoadjuvant regimens: Arm A (nab-pac 125 mg/m 2 / gem 1,000 mg/m 2 d1,8 q3w) vs.…”

Section: Patientsmentioning

confidence: 99%

“…To this end, we present a prospectively planned hypothesis‐generating translational analysis within the neoadjuvant WSG‐ADAPT‐TN trial. In this trial, the nab‐pac/carbo arm (12 weeks nab‐pac + carbo) was well tolerated, highly effective, with pCR of 46%, and superior to the nab‐pac/gem arm, with pCR of 29% . In addition to test superiority of the carbo arm, the trial aimed to identify early‐response markers as well as baseline predictors for pCR.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial

Gluz

Kolberg‐Liedtke

Prat

et al. 2019

Intl Journal of Cancer

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In the neoadjuvant WSG‐ADAPT‐TN trial, 12‐week nab‐paclitaxel + carboplatin (nab‐pac/carbo) was highly effective and superior to nab‐paclitaxel + gemcitabine (nab‐pac/gem) in triple‐negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients received 4 × nab‐pac 125 mg/m2 (plus carbo AUC2 or gem 1,000 mg/m2 d1,8 q21). Expression of 119 genes and PAM50 scores by nCounter were available in 306/336 pretherapeutic samples. Interim survival analysis was planned after 36 months median follow‐up. Basal‐like (83.3%) compared to other subtypes was positively associated with pCR (38% vs. 20%, p = 0.015), as was lower HER2 score (p < 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all p < 0.004), higher Ki‐67 (IHC; p < 0.001). For nab‐pac/carbo, expression of immunological (CD8, PD1 and PFDL1) genes and proliferation markers (proliferation and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3 and TYMS) were positively associated with pCR (p < 0.05 for all). For nab‐pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: p = 0.05; FGFR4: p = 0.02; VEGFA: p = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event‐free survival: 92% vs. 71%, p < 0.001). In early TNBC, basal‐like subtype, higher Ki‐67 (IHC) and lower HER2 score were, associated with chemosensitivity. Chemoresistance pathways differed between the two taxane based combinations. Combination of proliferation/immune markers and PAM50 subtype could allow patient selection for further deescalated chemotherapy and/or immune treatment approaches.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial

Gluz

Kolberg‐Liedtke

Prat

et al. 2019

Intl Journal of Cancer

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“…In the WSG-ADAPT-TN trial [21], 336 TNBC patients were randomly assigned to nab-paclitaxel plus gemcitabine (arm A) versus nab-paclitaxel plus carboplatin (arm B), in an anthracycline-free regimen. pCR favored arm B (28.7 vs. 45.9%; p = 0.002), which shows the high efficacy and excellent tolerability of a neoadjuvant nab-paclitaxel plus carboplatin regimen in TNBC.…”

Section: Chemotherapy and Antiangiogenic Agentsmentioning

confidence: 99%

Standard Neoadjuvant Treatment in Early/Locally Advanced Breast Cancer

Pernaut¹,

Lopez²,

Ciruelos³

2018

Breast Care

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Effect of Denosumab Added to 2 Different nab-Paclitaxel Regimens as Neoadjuvant Therapy in Patients With Primary Breast Cancer

et al. 2022

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IMPORTANCEAdjuvant denosumab might improve disease-free survival in hormone receptor (HR)-positive primary breast cancer (BC). The optimal neoadjuvant nab-paclitaxel schedule in terms of efficacy and safety is unclear.OBJECTIVE To determine whether adding denosumab to anthracycline/taxane-containing neoadjuvant chemotherapy (NACT) increases the pathological complete response (pCR) rate and which nab-paclitaxel schedule is more effective in the NACT setting. DESIGN, SETTING, AND PARTICIPANTSThe GeparX was a multicenter, prospective, open-label, phase 2b, 2 × 2 randomized clinical trial conducted by GBG and AGO-B at 38 German sites between February 2017 and March 2019. The analysis data set was locked September 4, 2020; analysis was completed November 13, 2020. Patients had unilateral or bilateral primary BC, stage cT2-cT4a-d or cT1c, with either clinically node-positive or pathologically node-positive or HR-negative disease, or Ki-67 proliferation index greater than 20%, or ERBB2 (formerly HER2)-positive BC.INTERVENTIONS Patients were randomized to receive or not receive denosumab, 120 mg subcutaneously every 4 weeks for 6 cycles, and either nab-paclitaxel, 125 mg/m 2 weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles (8 doses), followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m 2 (every 2 weeks or every 3 weeks). Carboplatin was given in triple-negative BC (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in ERBB2-positive BC (ERBB2-positive substudy). MAIN OUTCOMES AND MEASURESThe primary outcome was pCR rates between arms for each randomization.RESULTS A total of 780 female (n = 779) and male (n = 1) patients (median [range] age, 49.0 [22-80] years) were randomized to the 4 treatment groups. The pCR (ypT0 ypN0) rate was 41.0% (90% CI, 37%-45%) with denosumab vs 42.8% (90% CI, 39%-47%) (P = .58) without denosumab, irrespective of BC subtype. Nab-paclitaxel weekly resulted in a significantly (significance level of α = .10) higher pCR rate of 44.9% (90% CI, 41%-49%) vs 39.0% (90% CI, 35%-43%) (P = .06) with nab-paclitaxel days 1 and 8 every 3 weeks. The pCR rates for nab-paclitaxel schedules in subgroups were only significantly different for TNBC (60.4% vs 50.0%; P = .06). Grade 3 to 4 toxic effects did not differ with or without denosumab. Nonhematologic toxic effects of grade 3 to 4 were higher with nab-paclitaxel weekly (33.7% vs 24.1%; P = .004). CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, denosumab added to anthracycline/taxane-based NACT did not improve pCR rates. Nab-paclitaxel at a dosage of 125 mg/m 2 weekly significantly increased the pCR rate compared with the days 1 and 8, every-3-weeks schedule overall and in TNBC, but generated higher toxicity.

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Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab-Paclitaxel+Gemcitabine in Triple-Negative Breast Cancer: Randomized WSG-ADAPT-TN Trial Results

Cited by 102 publications

References 45 publications

Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial

Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial

Standard Neoadjuvant Treatment in Early/Locally Advanced Breast Cancer

Effect of Denosumab Added to 2 Different nab-Paclitaxel Regimens as Neoadjuvant Therapy in Patients With Primary Breast Cancer

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