The pathologic complete responses were significantly improved with neoadjuvant atezolizumab in combination with nab-paclitaxel plus doxorubicin and cyclophosphamide compared with placebo and chemotherapyin patients with stage 2 or stage 3 triple-negative breast cancer.
The pathologic complete responses (pCRs) were significantly improved with neoadjuvant atezolizumab in combination with nab-paclitaxel (Abraxane) plus doxorubicin and cyclophosphamide compared with placebo and chemotherapy in patients with stage 2 or stage 3 triple-negative breast cancer (TNBC), according to the phase 3 IMpassion031 study presented during the 2020 ESMO Virtual Congress.1
Findings from the randomized, multi-center trial, which were simultaneously published in The Lancet, demonstrated that patients with early-stage disease who received the neoadjuvant atezolizumab and chemotherapy regimen achieved a pCR rate of 57.6% compared to 41.1% in the group who received the placebo plus chemotherapy regimen (P =.0044).2
“The combination of atezolizumab with neoadjuvant chemotherapy for stage 2-3 TNBC provides clinically meaningful pCR benefit with an acceptable safety profile independent of PD-L1 status,” said senior study author Nadia Harbeck, MD, PhD, head of the Breast Center at the University of Munich, during a virtual presentation of the data. “Thus, this new combination therapy may offer an improved curative treatment option for this patient population with high unmet medical need.”
Previously, results from the IMpassion130 trial demonstrated that adding atezolizumab to nab-paclitaxel improved progression-free survival (PFS) and overall survival (OS) in patients with PD-L1 positive metastatic TNBC with an acceptable safety profile compared with nab-paclitaxel alone. However, as Harbeck noted during her presentation, adding atezolizumab to the treatment regimen was associated with a benefit in the patient population, regardless of PD-L1 status.
Traditionally, treatments for early-stage TNBC in the neoadjuvant setting have comprised anthracycline-cyclophosphamide and taxane-based chemotherapy regimens. To compare the efficacy and safety of adding atezolizumab to nab-paclitaxel followed by doxorubicin plus cyclophosphamide compared with placebo and the subsequent chemotherapy regimen, Harbeck and colleagues recruited 455 patients from July 7, 2017 to September 24, 2019.
A total of 333 patients met eligibility criteria. Of the eligible patient population, 165 patients were randomly assigned to receive intravenous atezolizumab at 840 mg every 2 weeks plus nab-paclitaxel at 125 mg/m² every week for 12 weeks followed by doxorubicin at 60 mg/m² and cyclophosphamide at 600 mg/m² every 2 weeks for 8 weeks, which was then followed by surgery. The remaining patients randomly were assigned to receive placebo plus the chemotherapy regimen, which was also followed by surgery.
After a median follow-up of 20.6 months, 11 patients in the atezolizumab arm were either not treated (n = 1) or had discontinued neoadjuvant treatment (n = 10) prior to receiving surgery. Fifteen patients in the placebo arm were also not evaluable as 1 patient was not treated, and 14 patients discontinued treatment prior to surgery.
A pathologic complete response was observed in 68.8% of patients with PD-L1-positive disease (n = 77) who received atezolizumab compared with a pCR of 49.3% in a total of 75 patients who were treated with the placebo-chemotherapy regimen (P =.021). However, as Harbeck noted, this did not reach statistical significance.
A pCR benefit was also observed with atezolizumab in the PD-L1-negative population. Patients who received the atezolizumab-chemotherapy regimen (n = 88) achieved a pCR rate of 47.7% compared with a pCR rate of 34.4% in patients (n = 93) who received the placebo-chemotherapy regimen.
There appears to be a positive trend for atezolizumab plus the chemotherapy regimen in improving EFS, DFS and OS, however, Harbeck noted that the data are immature and further research is ongoing.
Almost all patients (99.4%) in the atezolizumab arm experienced at least one adverse event. Moreover, 100% of the placebo arm experienced at least one adverse event. Treatment related grade 3-4 adverse events were reported in 56.7% of patients who received the atezolizumab-chemotherapy regimen and 53.3% of patients who received the placebo regimen.
The most common adverse events in the neoadjuvant phase in both the atezolizumab and placebo arm included, but were not limited to, alopecia (75% vs. 77.2%, respectively), nausea (64.6% vs. 67.1%, respectively) and diarrhea (41.5% vs. 44.3%, respectively).
The most common adverse event of special interest of any grade was rash in both the atezolizumab arm (48.8%) and placebo arm (49.1%).
“The results of IMpassion031 showed that the combination of atezolizumab with a platinum-free neoadjuvant regimen improved pathological complete response rate,” the authors conclude in the study published in The Lancet. “This combination can also provide benefit to patients who are unfit for platinum-containing anthracycline-taxane-based neoadjuvant chemotherapy.”