Atezolizumab Fails to Help in High-Risk Triple-Negative Breast Cancer

Atezolizumab (Tecentriq) failed to improve outcomes when added to chemotherapy after surgery for patients with high-risk triple-negative breast cancer (TNBC), a study finds.1

This open-label international randomized phase 3 study is published in JAMA.

Atezolizumab plus chemotherapy after surgery did not improve survival in high-risk triple-negative breast cancer. | Image credit: Jennifer - stock.adobe.com

“To our knowledge, this is the only phase 3 randomized trial involving patients with high-risk early-stage TNBC to evaluate adding a PD-L1 or PD-1 inhibitor to adjuvant chemotherapy in patients who undergo surgery as their initial treatment,” wrote the researchers of the study. “Postoperative atezolizumab-mediated immune therapy did not add benefit to standard chemotherapy after surgery.”

Atezolizumab is an immunotherapy drug that works by binding to the protein PD-L1 on the surface of some cancer cells, which keeps cancer cells from suppressing the immune system.2 Indications include locally advanced or metastatic urothelial carcinoma, metastatic non-small cell lung cancer (NSCLC), extensive-stage small cell lung cancer, metastatic TNBC, and unresectable or metastatic hepatocellular carcinoma.3

In the study, the researchers aimed to evaluate the addition of immunotherapy in the form of atezolizumab to postoperative chemotherapy in patients with high-risk TNBC.1

The trial was conducted across more than 330 centers in 31 countries. Eligible participants had stage II or III disease and underwent surgery as their initial treatment. Between August 2, 2018, and November 11, 2022, a total of 2199 patients were randomized in a 1:1 ratio to receive either standard chemotherapy alone (n = 1098) or chemotherapy plus atezolizumab (n = 1101) for up to 1 year.

The primary endpoint was invasive disease-free survival, defined as the time from randomization to the occurrence of invasive breast cancer, recurrence elsewhere in the body, or death from any cause. The final analysis compared survival outcomes and treatment-related adverse events between the 2 groups.

The analysis found no significant benefit in adding atezolizumab to postoperative chemotherapy for patients with high-risk TNBC. After a median (IQR) follow-up of 32 (0-59) months, invasive disease-free survival events occurred in 12.8% of patients who received atezolizumab plus chemotherapy and 11.4% of those who received chemotherapy alone (HR, 1.11; 95% CI, 0.87-1.42; P = .38). These findings indicated that atezolizumab did not improve survival outcomes and, instead, was associated with a higher incidence of severe (grade 3 or 4) treatment-related adverse events (54% vs 44%). However, the rates of fatal adverse events (0.8% vs 0.6%) and chemotherapy discontinuation due to adverse effects were similar between the 2 groups.

The researchers acknowledged some limitations. First, it was discontinued early after 266 of the required 390 invasive disease-free survival events, which limited the ability to detect potential long-term benefits. Additionally, early termination shortened follow-up, leaving gaps in long-term safety data and the potential for late-onset adverse events. Furthermore, BRCA status was available for only about 20% of participants, and despite global enrollment, less than 1% of patients were Black, which limited the study's applicability to diverse populations.

Despite these limitations, given these results, the researchers concluded that immune therapy with atezolizumab did not provide additional benefit in preventing recurrence or improving survival in this patient population.

“The current trial provides the only results on cancer immunotherapy plus chemotherapy as adjuvant-only treatment, and no other immunotherapy trials are investigating this specific therapeutic approach,” wrote the researchers. Based on these results, patients who receive surgery before any chemotherapy should not receive atezolizumab with their postoperative chemotherapy.”

References

1. Ignatiadis M, Bailey A, McArthur H, et al. Adjuvant atezolizumab for early triple-negative breast cancer. JAMA. Published online January 30, 2025. Accessed January 29, 2025. https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2024.26886?guestAccessKey=dc14288b-a877-4855-833f-83140af45d19&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=013025.

2. Atezolizumab. NIH. Updated January 2, 2025. Accessed January 29, 2025. https://www.cancer.gov/about-cancer/treatment/drugs/atezolizumab.

3. Aleem A, Shah H. Atezolizumab. NIH. Updated October 29, 2024. Accessed January 29, 2025.

https://www.ncbi.nlm.nih.gov/books/NBK567758/#:~:text=Atezolizumab%20is%20a%20humanized%20IgG1,unresectable%20or%20metastatic%20hepatocellular%20carcinoma.