“You see responses, even in patients without expression of PD-L1 within the tumor, granted that these tumors might be archival tumors and PD-L1 being a dynamic marker, this might not reflect the true PD-L1 status at the time of treatment,” said Adams. “Responses seem to be higher in the PD-L1 enriched patients, but it has been encouraging not to be restricted to that group.”
After a median follow-up of 5.2 months for all 32 patients, grade 3/4 adverse events (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).
“The first-line confirmed responses were 67%, and this is the population of patients who will now be enrolled in the phase III study, which is randomizing patients to a nab-paclitaxel backbone plus or minus atezolizumab,” said Adams. “This phase III study is ongoing, and is called IMpassion130. This global study will hopefully bring immunotherapy to the market for patients with TNBC.”
In the phase III IMpassion130 trial, patients with previously untreated metastatic TNBC will be randomized to nab-paclitaxel plus placebo or atezolizumab. The primary endpoint of the study is progression-free survival in the full population and in a PD-L1-positive group. Secondary endpoints include overall survival, ORR, and duration of response. The target enrollment goal for the trial is 350 patients (NCT02425891).
Atezolizumab is a humanized IgG1 monoclonal antibody that is directed against PD-L1 to prevent the ligand from binding to PD-1 and B7.1. Inhibition of this signaling pathway prevents antitumor immune suppression, resulting in T-cell priming and restored tumor-specific T-cell immunity.
As a single-agent, atezolizumab demonstrated an ORR of 18% in pretreated patients with PD-L1-positive TNBC. Additionally, in other settings, including non–small cell lung cancer (NSCLC) and bladder cancer, the antibody demonstrated impressive efficacy, leading to several breakthrough therapy designations from the FDA.
Prior trials exploring nab-paclitaxel plus atezolizumab demonstrated high response rates for patients with NSCLC. Nab-paclitaxel offers an appealing option for combination strategies with immunotherapy, since the agent does not require premedication with steroids, which cause immunosuppresion. Additionally, preclinical models have shown synergy between the two agents.
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.
<<< View more from the 2015 San Antonio Breast Cancer Symposium