Neoadjuvant trial of nab-paclitaxel and atezolizumab (Atezo), a PD-L1 inhibitor, in patients (pts) with chemo-insensitive triple negative breast cancer (TNBC)

Abstract

Background: Achieving a residual cancer burden (RCB) 0-1 portends an excellent prognosis for TNBC pts receiving neoadjuvant (NACT) anthracycline (AC) and taxane chemotherapy while pts with high residual disease (RCB II-III) have a 40-80% recurrence risk. The GeparTrio and Aberdeen trials demonstrated that pts with poor response by ultrasound (US) during NACT had pathologic complete response (pCR) rates of 2-5% even if NACT was changed based on US response. Immunotherapy is a promising strategy for chemo-insensitive TNBC; however, given toxicity and potential for long-term morbidity, pt selection is important. Methods: Pts identified as having chemo-insensitive TNBC with AC using US or through previous participation in a separate trial, ARTEMIS, were eligible. To identify insensitive TNBC, ARTEMIS used an algorithm combining a CLIA-certified chemosensitivity mRNA gene signature with US response to AC X4. Eligible pts then received weekly nab-paclitaxel (100 mg/m2 IV for 12 weeks) and atezo (1200mg IV q 3 weeks). Atezo continued for 3months after surgery. Using a 2-stage Gehan-type design, if>1 pt had an RCB 0-I in the first 19, the protocol would continue to accrue a total of 37 pts to estimate an RCB-0/I rate for atezo + nab-paclitaxel in chemo-insensitive TNBC for future trials. We report the interim analysis of the first 19 pts. Results: 19 pts enrolled from 02/2016- 12/12/2017. One pt received 1 cycle, then withdrew consent. Median age was 54 (range 35-75). Presenting clinical stage was II in 7 pts and III in 12 pts. Final pathology status was: RCB 0=5; RCB I=1; RCB II=5 and RCB III=7. RCB 0-I=6/19 (32%). Toxicity included 6 serious adverse events in 3 pts: fever, elevated creatinine and post-surgical pain. Most common toxicities included fatigue, neuropathy, pain, anemia, rash, elevated transaminases, hyperglycemia, nausea and dyspnea. Six pts required atezo to be held and/or discontinued. Conclusions: The combination of nab-paclitaxel and atezo resulted in moderate toxicity but increased the expected RCB 0-I rates from 5% to 32% for TNBC patients with chemotherapy-insensitive disease. Given these promising results, this study will continue to full accrual.