Sandra Horning, MD
Upfront treatment with atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) significantly reduced the risk of disease progression or death compared with nab-paclitaxel alone in patients with metastatic or unresectable locally advanced triple-negative breast cancer (TNBC), according to topline results from the phase III IMpassion130 study.
In the serial biopsy arm, a pretreatment biopsy was taken ≥7 days before the first cycle. Additional biopsies were obtained between days 10 and 15 during the first cycle then again 4 weeks after the first dose of atezolizumab. Responses were confirmed if seen on two or more sequential scans. The primary endpoint of the study was safety, with key secondary endpoints focused on ORR, duration of response, progression-free survival, and biomarker analyses.
The median age of patients in the study was 55.5 years, and most had an ECOG PS of 0 (19%) or 1 (81%). The number of prior systemic therapies received was 5, although a group of patients were enrolled in the frontline setting (n = 9). Prior to entering the study, 87% of patients had received a taxane.
At the time of the data cutoff, 24 patients with a minimum follow-up of ≥3 months were evaluable for efficacy. Across all groups, when considering unconfirmed responses, the ORR was 70.8%, which included a complete response rate of 4.2%. Additionally, the stable disease rate was 20.8%, for an overall disease control rate of 91.6%. At the time of the analysis, 11 of 17 responses (65%) remained ongoing.
In the frontline setting, the confirmed/unconfirmed ORR was 88.9% for nab-paclitaxel and atezolizumab. The complete response in the frontline setting was 11.1%. In the second-line setting, the ORR was 75% and in the third-line setting or beyond the ORR was 42.9%, which consisted of all partial responses.
For the biomarker analysis, PD-L1 expression in archival and fresh tumor specimens were centrally evaluated by immunohistochemistry using the Ventana PD-L1 assay. Levels were examined on both tumor cells and immune cells. Additionally, blood was analyzed for changes in proliferating CD8+ T cells.
In this analysis, activated CD8+ T cells transiently peaked at the end of the first cycle of atezolizumab. Moreover, PD-L1 expression appeared to be primarily restricted to immune cells. Out of those evaluable for efficacy (n = 24), 9 had PD-L1 expression on immunes cells, 7 were negative for PD-L1, and 8 had unknown biomarker status.
In patients with PD-L1–positive TNBC, the ORR was 77.8% and the stable disease rate was 22.2%. In the unknown biomarker arm, the ORR was 75%, which included 1 complete response and 2 patients with progressive disease. In the PD-L1–negative group, the ORR was 57.1% and the stable disease rate was 42.9%.
After a median follow-up of 5.2 months for all 32 patients, grade 3/4 AEs had occurred in 56% of patients, including neutropenia (41%), thrombocytopenia (9%), and anemia (6%). At least one AE of any grade occurred in all patients in the trial.
Overall, there were no treatment-related deaths observed in the study. Five patients discontinued nab-paclitaxel as a result of an AE. Per the protocol, these patients continued single-agent atezolizumab. Treatment discontinuations were related to fatigue (n = 1; grade 2), asthenia (n = 1; grade 2), and peripheral neuropathy (n = 3; grade 1, 2, and 3).
Adams S, Diamond J, Hamilton E, et al. Safety and clinical activity of atezolizumab (anti-PDL1) in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer. Presented at: San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. Abstract P2-11-06.