WSG-ADAPT TN: Neoadjuvant Albumin-Bound Paclitaxel + Carboplatin or Gemcitabine in TNBC CCO Independent Conference Coverage*: The 2015 Annual Meeting of the CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2015 San Antonio, Texas *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. TNBC, triple-negative breast cancer. This program is supported by educational grants from Genentech and Novartis.

WSG-ADAPT TN: Background pCR predicts improved outcomes in TNBC[1] Optimal therapy for TNBC not established Albumin-bound paclitaxel: Increased pCR rate vs paclitaxel in pts with early BC, particularly TNBC (OR: 2.69)[2] When combined with gemcitabine increased OS vs gemcitabine in metastatic pancreatic cancer[3] When combined with carboplatin increased ORR vs paclitaxel + carboplatin in advanced NSCLC[4] Current report assessed efficacy and safety of albumin-bound paclitaxel + either gemcitabine or carboplatin as neoadjuvant therapy in TNBC[5] BC, breast cancer; NSCLC, non-small-cell lung cancer; OR, odds ratio; pCR, pathological complete response; TNBC, triple-negative breast cancer. 1. Cortazar P, et al. Lancet. 2014;384:164-172. 2. Untch M, et al. SABCS 2014. Abstract S2-07. 3. Von Hoff DD, et al. N Engl J Med. 2013;369:1691-1703. 4. Socinski MA, et al. J Clin Oncol. 2012;30:2055-2062. 5. Gluz O, et al. SABCS 2015. Abstract S6-07. Slide credit: clinicaloptions.com

WSG-ADAPT TN: Study Design Biopsy at Baseline and Wk 3 Wk 12 Albumin-Bound Paclitaxel 125 mg/m2 + Gemcitabine 1000 mg/m2* (n = 182) Surgery or biopsy† Pts with TNBC, no distant metastasis, LVEF ≥ 50% or within normal limits (N = 336) Albumin-Bound Paclitaxel 125 mg/m2 + Carboplatin AUC2* (n = 154) AUC, area under the curve; EC, epirubicin, cyclophosphamide; EFS, event-free survival; LVEF, left ventricular ejection fraction; pCR, pathologic complete response; TNBC, triple-negative breast cancer. *Treatment given in 4 cycles in both arms at Wks 1, 2, 4, 5, 7, 8, 10, 11. †Standard chemotherapy (4 x EC) recommended after surgery or 12-wk biopsy (if clinical non-pCR). Primary endpoint: pCR (ypT0/is ypN0) Secondary endpoints: pCR by early response, EFS, OS, safety Slide credit: clinicaloptions.com Gluz O, et al. SABCS 2015. Abstract S6-07.

WSG-ADAPT TN: Baseline Characteristics Albumin-Bound Paclitaxel + Gemcitabine (n = 182) Albumin-Bound Paclitaxel + Carboplatin (n = 154) Median age, yrs (range) 50 (26-75) 52 (29-76) cT, % 1 ≥ 2 37.4 62.6 37.0 62.9 cN, % ≥ 1 74.2 25.8 73.4 26.6 Median Ki67, % 75 70 Central grade 3, % 94.5 90.9 Slide credit: clinicaloptions.com Gluz O, et al. SABCS 2015. Abstract S6-07.

WSG-ADAPT TN: pCR Albumin-bound paclitaxel + carboplatin significantly increased pCR vs albumin-bound paclitaxel + gemcitabine Consistent benefit across cT, Ki67, and menopausal subgroups pCR more likely in pts with an early response (44.4% vs 19.5%; P < .001) This effect seen regardless of treatment arm pCR, n/N (%) Albumin-Bound Paclitaxel + Gemcitabine Albumin-Bound Paclitaxel + Carboplatin P Value All pts 51/178 (28.7) 67/146 (45.9) < .001 Pts with early response 26/72 (36.1) 38/72 (52.8) NR Pts without early response 10/74 (13.5) 13/44 (29.5) NR, not reported; pCR, pathologic complete response. Slide credit: clinicaloptions.com Gluz O, et al. SABCS 2015. Abstract S6-07.

WSG-ADAPT TN: Safety Dose reduction more frequent with albumin-bound paclitaxel + gemcitabine vs albumin-bound paclitaxel + carboplatin (20.6% vs 11.9%, respectively) Fewer serious AEs, CTC grade ≥ 3 with albumin-bound paclitaxel + carboplatin AEs, % Albumin-Bound Paclitaxel + Gemcitabine (n = 182) Albumin-Bound Paclitaxel + Carboplatin (n = 154) Serious AEs 17.2 10.6 Treatment-related serious AEs 5.3 CTC grade ≥ 3 Neutropenia Febrile neutropenia Infections Increased ALT Polyneuropathy 15.0 6.1 11.7 0.6 14.6 0.7 1.3 3.3 AE, adverse event; ALT, alanine aminotransferase; CTC, common toxicity criteria. Slide credit: clinicaloptions.com Gluz O, et al. SABCS 2015. Abstract S6-07.

WSG-ADAPT TN: Conclusions 12 wks of albumin-bound paclitaxel + carboplatin significantly increased pCR vs albumin-bound paclitaxel + gemcitabine in pts with TNBC pCR more likely in pts with early response at Wk 3 biopsy regardless of study treatment Fewer serious AEs, CTC grade ≥ 3, with albumin- bound paclitaxel + carboplatin AE, adverse event; CTC, common toxicity criteria; pCR, pathologic complete response; TNBC, triple-negative breast cancer. Slide credit: clinicaloptions.com Gluz O, et al. SABCS 2015. Abstract S6-07.

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