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No higher pathologic complete response with atezolizumab added to chemotherapy

SABCS 2019

Adding atezolizumab to nab-paclitaxel and carboplatin did not significantly increase the rate of pathologic complete response in women with triple-negative breast cancer. However, in multivariate analyses, the presence of programmed death-ligand 1 (PD-L1) expression was the most significant factor influencing the rate of pathological complete response.

Triple-negative breast cancer of high proliferation or grade is a subgroup characterised by very poor prognosis, rapid progression to metastatic stage, and rapid onset of resistance to chemotherapy after initial response. As a whole, triple-negative breast cancer represents a specific area of medical need, in which new therapeutic approaches need to be thoroughly evaluated to provide new options for this specific patient population. Immune infiltration of triple-negative breast cancer is linked to prognosis and probability of response to chemotherapy. Blockade of PD-L1 or programmed cell death protein 1 (PD-1) may favour durable responses of triple-negative breast cancer by immune mechanism themselves, and in combination with classical chemotherapy.

The IMpassion130 study showed significant progression-free survival (PFS) benefit with the addition of the PD-L1 antibody atezolizumab to nab-paclitaxel in PD-L1-positive metastatic triple-negative breast cancer [1,2]. Gianni et al. designed a multicentre, open-label study to assess the role of atezolizumab in triple-negative breast cancer patients [3]. The primary aim of the study was to compare event-free survival (EFS) 5 years after randomisation of the last patient. Secondary aim was the rate of pathologic complete response (which is defined as the absence of invasive cells in breast and lymph nodes); the primary population for all efficacy endpoints was the intention-to-treat (ITT) population. Other secondary aims were tolerability of the regimens, studies on putative predictive markers of benefit, and resistance to the study regimens. Eligible patients had human epidermal growth factor receptor 2 (HER2)-negative, oestrogen receptor (ER)-negative, and progesterone receptor (PR)-negative, early high-risk (T1cN1; T2N1; T3N0) or locally advanced unilateral breast cancer. A total of 280 patients with triple-negative breast cancer were randomised to neoadjuvant carboplatin AUC2 + nab-paclitaxel 125 mg/m2 intravenously on days 1 and 8, with atezolizumab (n=138) or without atezolizumab 1,200 mg intravenously (n=142) on day 1. Both regimens were given every 3 weeks for 8 cycles and were followed by surgery and by 4 cycles of an anthracycline regimen as per the investigator’s choice. Baseline characteristics were comparable between the 2 groups. Overall, 51% of patients had early high-risk disease, 49% had local advanced disease, 56% was PD-L1-positive, median age was 50 years, and 13% had cN0.

Results from the ITT analysis showed that 43.5% of patients who received atezolizumab had pathologic complete response versus 40.8% of those who did not receive atezolizumab, resulting in a difference of 2.63 (95% CI 14.0-8.8) and an OR of 1.11 (95% CI 0.69-1.79; P=0.66). The difference in pathologic complete response between those who were PD-L1-positive and patients who were PD-L1-negative was 51.9% versus 32.2% for those receiving atezolizumab and 48.0% versus 32.3% for those who did not receive atezolizumab, respectively. With regard to disease stage, comparing early high-risk versus locally advanced disease, the rates were 44.9% versus 42.0% for those receiving atezolizumab and 39.7% versus 42.0% for those not receiving atezolizumab, respectively. The clinical overall response is shown in the Table. Overall disease progression during neoadjuvant treatment occurred in 5.8% of patients who were treated with atezolizumab versus 8.4% of patients receiving only chemotherapy. Locoregional disease progression occurred in 2.9% versus 6.3% of patients and distant disease progression occurred in 2.9% versus 2.1% of patients.

Table. Clinical overall response with and without atezolizumab treatment [3]

Treatment-related adverse events with an incidence of ≥15% were similar for both groups except for a significantly higher overall incidence of serious adverse events and liver transaminase abnormalities with atezolizumab. Patient follow-up will be continued to allow for assessing comparative long-term EFS and OS analyses, and molecular studies are planned as well.

1. Schmid P, et al. N Engl J Med. 2018; 379:2108-2121.
2. Schmid P, et al. Abstract 1003. ASCO 2019.
3. Gianni L, et al. GS3-04. SABCS 2019.

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