Background: Metastatic triple-negative breast cancer (mTNBC) is associated with poor prognosis, and chemotherapy remains the mainstay of treatment. Cancer immunotherapy represents a promising treatment approach for mTNBC, which is characterized by a high mutation rate, increased levels of tumor-infiltrating lymphocytes and high programmed death ligand-1 (PD-L1) expression levels. Atezolizumab (atezo; MPDL3280A) is a humanized monoclonal antibody that can restore tumor-specific T-cell immunity by inhibiting the binding of PD-L1 to PD-1. Atezo has demonstrated durable responses as monotherapy in mTNBC (Emens et al, AACR 2015). In addition, high objective response rates (ORRs) and durable responses have been observed with atezo plus chemotherapy in patients with non-small cell lung cancer (Liu et al, ASCO 2015). This study is the first combination trial of a checkpoint inhibitor with chemotherapy in patients with mTNBC.
Methods: This arm of a multicenter, multi-arm Phase Ib study (NCT01633970) evaluated atezo in combination with weekly nab-paclitaxel in patients with mTNBC. Primary endpoints were safety and tolerability, with secondary endpoints of PK and clinical activity. Key eligibility criteria included measurable disease, ECOG PS 0/1 and ≤ 2 prior cytotoxic regimens. Patients received atezo 800 mg q2w (days 1 and 15) with nab-paclitaxel 125 mg/m2 q1w (days 1, 8 and 15) for 3 weeks in 4-week cycles, continued until loss of clinical benefit. If nab-paclitaxel was discontinued due to toxicity, atezo could be continued as monotherapy. ORR was assessed by RECIST v1.1. PD-L1 expression was scored at 4 diagnostic levels based on PD-L1 staining on tumor cells and tumor-infiltrating immune cells with the SP142 immunohistochemistry assay.
Results: As of February 10, 2015, 11 patients were evaluable for safety. All patients were women with a median age of 58 y (range, 32-75 y). No unexpected or dose-limiting toxicities were observed. The median duration of safety follow-up was 79 days (range, 27-182 days). The efficacy-evaluable population consisted of 5 patients who had ≥ 1 scan and ≥ 3 months follow-up. Four PRs and 1 SD were observed. By the next data cutoff of June 15, 2015, 21 patients will have been enrolled (7 in the safety cohort and 14 in the expansion cohort). All patients in the expansion cohort were required to undergo serial biopsies for correlative analyses. Approximately 21 and 19 patients will be evaluable for safety and efficacy, respectively. Updated safety, efficacy and biomarker data will be presented.
Conclusions: Preliminary results indicate that the combination of atezo plus nab-paclitaxel is tolerable with promising activity in patients with mTNBC. Based on these results and the observed activity of single-agent atezo in these patients, the combination of atezo and nab-paclitaxel is being evaluated in a Phase III study (NCT02425891) of patients with previously untreated mTNBC. Sponsor: Genentech, Inc. ClinicalTrials.gov: NCT01633970.
Citation Format: Adams S, Diamond J, Hamilton E, Pohlmann P, Tolaney S, Molinero L, Zou W, Liu B, Waterkamp D, Funke R, Powderly J. Safety and clinical activity of atezolizumab (anti-PDL1) in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-11-06.