Neoadjuvant Atezolizumab/Chemo Combo Improves pCR in Early TNBC

The combination of atezolizumab (Tecentriq), and nab-paclitaxel (Abraxane), followed by doxorubicin and cyclophosphamide, demonstrated a statistically significant and clinically meaningful improvement in pathological complete response (pCR) compared with placebo plus chemotherapy as a neoadjuvant treatment for patients with early triple-negative breast cancer (TNBC), regardless of PD-L1 expression, meeting the primary end point of the phase 3 IMpassion031 trial (NCT03197935).¹

Moreover, safety for the atezolizumab combination appeared to be consistent with the known safety profiles of each agent alone, and no new safety signals were identified. Full findings of the IMpassion031 study will be presented at an upcoming medical meeting, and will also be discussed with the FDA and the European Medicines Agency.

“Triple-negative breast cancer remains an aggressive disease with high rates of recurrence,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Roche, the developer of atezolizumab, stated in a press release. “Our goal in treating TNBC at its earliest stages is to provide people with the best chance for a future cure. Adding Tecentriq to chemotherapy now has the potential to help women with TNBC at multiple different stages of the disease.”

In the multicenter, double-blind, phase 3 IMpassion031 trial, investigators evaluated the efficacy and safety of atezolizumab in combination with nab-paclitaxel, followed by doxorubicin and cyclophosphamide, versus placebo plus chemotherapy in 333 patients with previously untreated, early TNBC.

To be eligible for enrollment, patients must have had an ECOG performance status of 0 or 1, a primary breast tumor size greater than 2 cm, adequate hematologic and end-organ function, and had cT2 to cT4, cN0-cN3, or cM0 disease. Those with a prior history of invasive breast cancer, metastatic disease, prior therapy with anthracyclines or taxanes, and a history of ductal carcinoma in situ, among other criteria, were excluded from enrolling on the study.

Patients were randomized 1:1 to receive the atezolizumab or placebo regimen in the neoadjuvant setting; on the atezolizumab arm, treatment with the PD-L1 inhibitor continued at 1200 mg intravenously (IV) every 3 weeks for 11 doses in the adjuvant setting. In the neoadjuvant setting, atezolizumab was given at 840 mg IV every 2 weeks, while nab-paclitaxel was given at 125 mg/m² IV weekly for 12 weeks. Atezolizumab was then given at the same dosage in combination with doxorubicin at 60 mg/m² and cyclophosphamide at 600 mg/m² every 2 weeks IV with support from filgrastim (Neupogen) or pegfilgrastim (Neulasta) for 4 doses.

The primary end point is pCR using the American Joint Committee on Cancer staging system in the intent-to-treat population and in the PD-L1–positive population. Secondary end points include overall survival (OS), event-free survival, disease-free survival, and quality of life measures.

The IMpassion031 study is the second positive phase 3 trial showcasing a benefit with atezolizumab in TNBC. In March 2019, the FDA approved the combination of atezolizumab and nab-paclitaxel for the treatment of adults with unresectable locally advanced or metastatic TNBC in people whose tumors express PD-L1 on immune cells at 1% or higher.

The approval is based on findings from the phase 3 IMpassion130 trial, in which the combination led to a 40% reduction in the risk of disease progression or death compared with nab-paclitaxel alone in this patient population.2

Data from the initial progression-free survival (PFS) analysis in the PD-L1–positive population showed a median PFS of 7.4 months versus 4.8 months with atezolizumab/nab-paclitaxel versus nab-paclitaxel alone, respectively (HR, 0.60; 95% CI, 0.48-0.77; P <.0001).

Additionally, an interim analysis of the PD-L1–positive population demonstrated a clinically meaningful improvement in OS with the combination at 25.0 months versus nab-paclitaxel alone at 15.5 months, respectively (HR, 0.62; 95% CI, 0.45-0.86). At 2 years, the OS rates in the intent-to-treat population were 42% and 39%, respectively.

Two-year OS rates were higher in the PD-L1–expressing population at 51% in the atezolizumab arm versus 37% in the chemotherapy-alone arm.

References

1. Roche’s Tecentriq in combination with chemotherapy (including Abraxane) meets primary endpoint of improved pathological complete response, regardless of PD-L1 status, as initial treatment for people with early triple-negative breast cancer [news release]: Basel, Switzerland. Roche. Published June 18, 2020. https://bit.ly/2AMHXtB. Accessed June 18, 2020.
2. Schmid P, Adams S, Rugo HS, et al. IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab (atezo) + nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 2019;37(suppl 15; abstr 1003). doi:10.1200/JCO.2019.37.15_suppl.1003