IMpassion031: Neoadjuvant atezolizumab plus chemo improves pCR rates in early TNBC

Pathologic complete response (pCR) rates have significantly improved in patients with early-stage triple-negative breast cancer (TNBC) on neoadjuvant atezolizumab plus chemotherapy regardless of programmed death-ligand 1 (PD-L1) status, with an acceptable safety profile, relative to those on chemotherapy alone, results from the Impassion031 study have shown.

Patients aged 18 years with previously untreated, centrally confirmed, invasive stage II-III early-stage TNBC and tumour size >2 cm were included in this study, which was presented at the ESMO Asia Virtual Congress 2020 (ESMO Asia 2020).

A total of 333 patients were randomly assigned to receive atezolizumab 840 mg (n=165) or placebo (n=168) once every 2 weeks (q2w) with nab-paclitaxel 125 mg/m² once weekly (qw) for six doses, followed by atezolizumab 840 mg or placebo q2w plus doxorubicin 60 mg/m² with cyclophosphamide 600 mg/m² q2w for four doses, followed by surgery.

The researchers, led by medical oncologist S. Saji from the Fukushima Medical University in Japan, assessed pCR in all patients after surgery. They were unblinded to study treatment. Patients were stratified according to diagnosis stage (II vs III) and PD-L1 expression on tumour-infiltrating immune cells (IC; ≥1 percent vs <1 percent).

Locally assessed pCR in intention-to-treat (ITT) or PD-L1+ (PD-L1 IC ≥1 percent) patients was the main endpoint, and event-free survival (EFS) was the secondary endpoint. Safety was also evaluated.

Over a median follow-up of 20.6 months in the atezolizumab+chemo and 19.8 months in the placebo+chemo arm, 57.6 percent (95 percent confidence interval [CI], 49.7–65.2) and 41.1 percent (95 percent CI, 33.6–48.9) of patients, respectively, achieved pCR (Δ16.5 percent, 95 percent CI, 5.9–27.1; one-sided p=0.0044 [significance boundary, 0.0184]; p=0.0085 for the intersection hypothesis of ITT and PD-L1+ populations). [ESMO Asia 2020, abstract 3MO]

In the PD-L1+ population (n=152), pCR was noted in 68.8 percent (95 percent CI, 57.3–78.9) of patients in the atezolizumab+chemo arm compared with 49.3 percent (95 percent CI, 37.6–61.1) in the placebo+chemo group (Δ19.5 percent, 95 percent CI, 4.2–34.8; one-sided p=0.021; not significant).

Neither the atezolizumab nor the chemo alone arm reached the median EFS (hazard ratio, 0.76, 95 percent CI, 0.04–1.44). Grade 3/4 adverse events (AEs) were balanced in the neoadjuvant phase. In addition, 22.6 percent and 15.6 percent of patients, respectively, had treatment-related serious AEs. One patient in each group experienced an unrelated grade 5 AE.

These findings were consistent to those of a Philippines study, a meta-analysis of four randomized controlled trials which was also presented at the ESMO Asia 2020. The investigators reported the association of neoadjuvant immunotherapy plus chemotherapy with increased pCR rates in patients with early-stage TNBC. [ESMO Asia 2020, abstract 10P]

“Subgroup analysis showed that the benefit of adding immunotherapy was more significant in those with PD-L1-expressing tumours,” the investigators said. “This result indicates that the PD-L1 immune marker may have utility in selecting TNBC patients who can benefit more from PD-L1 inhibitors.”

“Longer follow-up and further analysis of these studies would hopefully demonstrate significance in other outcomes such as progression-free survival and overall survival,” they added.

Impassion031 was a global, phase III, multicentre, double-blind, randomized, placebo-controlled study of patients with high-risk primary invasive early-stage TNBC, which examined the efficacy and safety of neoadjuvant atezolizumab or placebo with nab-paclitaxel followed by atezolizumab or placebo with dose-dense doxorubicin plus cyclophosphamide.