Episode 7: IMpassion031 at ESMO BREAST 2023
The IMpassion 031 trial explored the potential benefits of neoadjuvant and adjuvant therapy involving atezolizumab for patients with stage 2 or stage 3 early-stage Triple Negative Breast Cancer (TNBC). Carlos Barrios presented the results of this small phase 3 trial at ESMO BREAST 2023.
The study’s design is notable for utilising a chemotherapy backbone comprising paclitaxel albumin followed by a dose-dense AC regimen, without the inclusion of platinum administration. It’s essential to consider that the study was unblinded both for participants and surgeons after surgery. Both groups received adjuvant salvage chemotherapy, and there was no control group that received no adjuvant therapy.
The primary outcome of the trial was primarily powered for pathological complete response (pCR) and had been presented previously. In both the intent-to-treat and the PD-L1 responsive subgroup (comprising about 46% of the total patients), the results showed a significant improvement in pCR rates compared to the placebo.
The results presented at ESMO BREAST 2023 pertain to secondary outcomes and are primarily descriptive. A noteworthy observation is an imbalance in adjuvant chemotherapy administration between the experimental and control arms, with one in five patients receiving adjuvant chemotherapy in the experimental arm compared to one in three in the control arm. This imbalance prevented formal testing of the results.
Although the hazard ratios suggested a trend favouring atezolizumab treatment, these results did not demonstrate a significant improvement in event-free survival, disease-free survival, or early overall survival data.
Interpreting the study’s outcome is challenging due to the lack of significant data. However, it did confirm the adverse prognostic impact of having circulating tumour DNA (ctDNA) positivity in the plasma at surgery.
The consensus among experts is that the trial was not adequately powered for survival events and was too small to yield significant results. Given that atezolizumab only improved the pCR rate, it’s unlikely to lead to registration for early or locally regionally advanced operable disease. Furthermore, the large phase 3 registration trial, IMpassion 030, which studied adjuvant atezolizumab, was discontinued prematurely due to futility.
In summary, while the results contribute to the body of evidence regarding immune checkpoint inhibitors in early TNBC when initiated in the neoadjuvant setting, they are unlikely to have a substantial impact on clinical practice.