medwireNews: Combining atezolizumab with standard neoadjuvant chemotherapy achieves significantly higher pathologic complete response (pCR) rates than chemotherapy alone in individuals with stage II–III triple-negative breast cancer (TNBC), indicates the IMpassion031 trial.
These phase 3 findings were presented at the ESMO Virtual Congress 2020 and simultaneously published in The Lancet.
Describing the pCR benefit as “clinically meaningful,” the study presenter commented that “this new combination may offer an improved curative option for this patient population with a high unmet medical need.”
Nadia Harbeck explains why the IMpassion031 results cement the role of neoadjuvant immunotherapy plus chemotherapy in early-stage triple-negative breast cancer (2:54)
In the double-blind study, 333 patients with early-stage TNBC (primary tumor >2 cm) were randomly assigned to receive a 12-week course of neoadjuvant atezolizumab 840 mg or placebo every 2 weeks alongside weekly nab-paclitaxel 125 mg/m2. This was followed by the same dose of atezolizumab or placebo together with doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 2 weeks for a further 8 weeks. Following surgery and subsequent study unblinding, patients in the atezolizumab group continued treatment with the PD-L1 inhibitor at a dose of 1200 mg every 3 weeks for 11 cycles, while those in the placebo group underwent observation.
As reported by Nadia Harbeck (University of Munich, Germany), the co-primary endpoint of pCR in the intention-to-treat population was significantly higher with atezolizumab than placebo, at rates of 57.6% and 41.1%, respectively, after a median follow-up of around 20 months.
The other primary endpoint of pCR in the PD-L1-positive (≥1 PD-L1-expressing tumor infiltrating immune cells) population was numerically higher in the atezolizumab than placebo group, at 68.8% versus 49.3%, but the difference did not cross the prespecified significance boundary.
The corresponding pCR rates in the PD-L1-negative subgroup were 47.7% and 34.4%.
The trends for time to event analyses, such as those for event-free, disease-free, and overall survival, favored atezolizumab, but “it is still too early to come up with definite conclusions,” commented Harbeck.
The toxicity profile of the atezolizumab–chemotherapy combination was as expected based on the known profiles of the individual study drugs, she said, adding that “commonly reported adverse events [AEs] were relatively similar between arms and mostly driven by chemotherapy.”
Treatment-related AEs of grade 3 or 4 occurred in 56.7% of atezolizumab-treated patients and 53.3% of those given placebo, with neutropenia the most frequent event of this severity in both groups, at 23.3% and 21.6%, respectively, followed by decreased neutrophil count (12.2 vs 11.4%) and febrile neutropenia (11.0 vs 9.0%).
The incidence of grade 3 or 4 AEs of special interest was 14.6% and 12.0% in the atezolizumab and placebo groups, respectively, with rash being most common in both (3.7 vs 3.6%).
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ESMO Virtual Congress 2020: 19–21 September
Lancet 2020; doi:10.1016/S0140-6736(20)31953-X