Phase II Trial of Neoadjuvant Carboplatin and Nab-Paclitaxel in Patients with Triple-Negative Breast Cancer

• DOI: 10.1002/onco.13574
• Publication Date: 2020-10-24T07:51:02Z
• Authors: Yuan Yuan; Jin Sun Lee; Susan E. Yost; Sierra Min Li; Paul H. Frankel; Christopher Ruel; Daniel Schmolze; Kim Robinson; Aileen Tang; Norma Martinez; Daphne Stewart; James Waisman; Laura Kruper; Veronica Jones; Andrea Menicucci; Sahra Uygun; Erin Yoder; Bastiaan van der ...; John H. Yim; Christina Yeon; George Somlo; Joanne Mortimer
• Keywords: Triple-negative breast cancer; Carboplatin; Nab-paclitaxel; Triple negative; Neoadjuvant Therapy

Abstract Background In this phase II clinical trial, we evaluated the efficacy of nonanthracycline combination carboplatin and nab-paclitaxel in early stage triple-negative breast cancer (TNBC). Patients Methods with newly diagnosed II–III TNBC (n = 69) were treated neoadjuvant (area under curve 6) every 28 days for four cycles plus (100 mg/m2) weekly 16 weeks. Pathological complete response (pCR) residual burden (RCB) analyzed germline mutation status, tumor-infiltrating lymphocytes (TILs), molecular subtype, GeparSixto immune signature (GSIS). Results Sixty-seven patients evaluable safety response. Fifty-three (79%) experienced grade 3/4 adverse events, including 3 anemia (43%), neutropenia (39%), leukopenia (15%), thrombocytopenia (12%), fatigue (7%), peripheral neuropathy (16%), (1%). Twenty-four (35%) had at least one dose delay, 50 (72%) required reduction. Sixty-three (94%) completed scheduled treatment. The responses as follows: 32 67 (48%) pCR (RCB 0), 10 (15%) RCB I, 19 (28%) II, 5 (7%) III, 1 (2%) progressed no surgery. Univariate analysis showed that immune-hot GSIS DNA repair defect (DRD) associated higher odds ratios 4.62 (p .005) 4.76 .03), respectively, 0/I versus II/III ratio 4.80 .01). Immune-hot was highly correlated DRD status TIL level < .001), subtype .001). After adjusting age, race, stage, grade, remained class 7.19 (95% confidence interval [CI], 2.01–25.68; p .002) 8.95 CI, 2.09–38.23; .003), respectively. Conclusion high-risk manageable toxicity encouraging antitumor activity. is rate 0/1. This study provides an additional rationale using platinum-based therapy future trials TNBCs. Clinical trial identification number: NCT01525966 Implications Practice Platinum important chemotherapy agent treatment study, well tolerated effective TNBC, resulting pathological 48%. univariate multivariate analyses tumor “immune-hot” (GSIS) association holds promise de-escalating TNBC. Although not routinely used clinic, further development into a clinically applicable assay indicated.