A ground breaking international clinical trial published in JAMA has found that adding the immunotherapy drug atezolizumab to standard chemotherapy does not improve outcomes for patients with early-stage triple-negative breast cancer (TNBC) who have undergone surgery. The findings, published from the ALEXANDRA/IMpassion030 trial, underscore the importance of treatment timing and may shift future approaches to immunotherapy in breast cancer care.
TNBC is an aggressive subtype of breast cancer characterised by the absence of oestrogen and progesterone receptors and the lack of HER2 protein overexpression. It disproportionately affects younger women and non-Hispanic Black women, with a high risk of recurrence and metastasis even after aggressive chemotherapy. Historically, about one-third of patients with stage II or III TNBC experience a metastatic recurrence within two to three years of diagnosis, and survival rates remain poor.
The ALEXANDRA/IMpassion030 trial, a phase 3 international, open-label, randomised study, aimed to determine if adding atezolizumab—a PD-L1 immune checkpoint inhibitor—to standard adjuvant chemotherapy could reduce recurrence rates in early-stage TNBC. The trial included 2,199 patients from 31 countries, all of whom had stage II or III TNBC and had undergone surgery prior to treatment.
Participants were randomised to receive either standard chemotherapy alone or chemotherapy combined with atezolizumab, followed by maintenance atezolizumab for up to one year. The primary goal was to improve invasive disease-free survival (DFS), a measure of time until cancer recurrence or death.
Despite hopes that atezolizumab could enhance outcomes, the final analysis showed no significant benefit. Invasive DFS events occurred in 12.8% of patients in the atezolizumab group compared to 11.4% in the chemotherapy-only group. The hazard ratio for invasive DFS was 1.11, indicating no improvement in patient outcomes.
In addition to the lack of efficacy, the study highlighted safety concerns. Patients receiving atezolizumab experienced higher rates of severe adverse events (54% vs. 44%) and serious treatment-related side effects (19% vs. 10%) compared to those on chemotherapy alone. Common side effects included diarrhea, rash, and hypothyroidism, with some cases severe enough to prompt discontinuation of treatment.
The negative results add to growing evidence that the timing of immunotherapy plays a critical role in its effectiveness. Earlier trials, such as the KEYNOTE-522 study, demonstrated significant improvements when immunotherapy was given before surgery (neoadjuvant therapy) and continued post-surgery. These results suggest that stimulating the immune system while the tumour is still present may be key to achieving better outcomes, as after surgery, the biological environment may not be as conducive to an effective immune response.
The study’s findings are expected to influence treatment guidelines, steering clinicians away from post-surgical immunotherapy in early-stage TNBC. Ongoing trials, such as the GeparDouze/NSABP B-59 study, will further explore the potential of preoperative immunotherapy in improving long-term outcomes.
For now, the standard of care for TNBC patients undergoing surgery first remains chemotherapy alone. However, the pursuit of more effective, tailored treatments continues, with researchers hopeful that future studies will unlock new strategies to combat this challenging disease.
Paper: Ignatiadis M, et al. Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial. JAMA. 2025 Jan 30:e2426886. doi: 10.1001/jama.2024.26886. Epub ahead of print. PMID: 39883436; PMCID: PMC11783246. Access online here.
Accompanying Editorial: Hunter NHurvitz S. Where Did the Passion Go?—Rethinking Adjuvant Immune Therapy for Triple-Negative Breast Cancer. JAMA. Published online January 30, 2025. doi:10.1001/jama.2024.26811. Access online here.
