Tecentriq Falls Short in Phase III Trial in Post-Surgery Triple-Negative Breast Cancer Patients

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The addition of the immune checkpoint inhibitor Tecentriq (atezolizumab) to postoperative chemotherapy was not found to improve treatment outcomes for patients with high-risk early-stage triple-negative breast cancer (TNBC), according to results from the Phase III ALEXANDRA/IMpassion030 trial (NCT03498716) published by JAMA Network Open.^1,2 These findings reinforce the use of preoperative chemoimmunotherapy followed by surgery in the treatment of these patients, according to the study authors.

“TNBC is associated with a high risk of progression to metastatic disease, higher incidence in younger women compared with other subtypes, and higher incidence in non-Hispanic Black women,” the study authors wrote. “Historically, approximately one-third of individuals with stage II or III TNBC experience a metastatic recurrence, despite receiving the best-available chemotherapy, within 2 to 3 years after an early-stage diagnosis, which, in turn, has a life expectancy of only 12 to 18 months. Consequently, innovation beyond conventional chemotherapy has been an unmet need.”¹

In prior clinical trials, Tecentriq, a PD-L1 monoclonal antibody, has been found to be safe and effective both as a monotherapy and in combination with anthracycline-based chemotherapy. The FDA has approved Tecentriq for non–small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma.³

Trial Design

The international, open-label, randomized ALEXANDRA/IMpassion030 trial analyzed the combination of Tecentriq plus standard adjuvant chemotherapy and continued as maintenance therapy in the treatment of early-stage TNBC. Eligibility requirements included being 18 years of age or older with nonmetastatic operable stage II or III TNBC.

The trial was conducted at over 330 centers across 31 countries. Patients initially treated with surgery for stage II or III TNBC were enrolled between August 2, 2018, and November 11, 2022.

All patients received standard chemotherapy consisting of 80 mg/m2 of paclitaxel each week for 12 weeks followed by investigator’s choice of either 60 mg/m² of dose-dense doxorubicin or 90 mg/m² of dose-dense epirubicin administered with 600 mg/m² of cyclophosphamide every two weeks for four cycles, along with granulocyte or granulocyte-macrophage colony-stimulating factor. Participants were randomly assigned in a 1:1 ratio to either 20 weeks of chemotherapy alone (n = 1098) or in combination with Tecentriq (n = 1101) administered at a dose 840 mg every two weeks for up to 10 doses, with an experimental group administered 1200 mg of maintenance Tecentriq every three weeks for up to one year total.

The trial’s primary end point was invasive disease-free survival (iDFS), with secondary endpoints that included iDFS in patients with PD-L1–positive (ICs ≥1%) and node-positive TNBC; overall survival; iDFS including second primary non–breast invasive cancer; recurrence-free interval; distant recurrence–free interval; DFS; and safety. All patients enrolled in the trial stopped treatment with Tecentriq after investigators performed a planned early interim and futility analysis, with the trial continuing to a premature final analysis.

At a median follow up of 32 months, iDFS events were reported in 12.8% of patients in the Tecentriq combination cohort compared to 11.4% patients in the chemotherapy alone cohort. The final stratified iDFS hazard ratio was 1.11 (95% CI, 0.87-1.42; P = .38). In terms of safety, 54% of patients in the Tecentriq with chemotherapy cohort experienced treatment-related grade 3 or 4 adverse events compared to 44% in the chemotherapy alone cohort.

“Postoperative atezolizumab-mediated immune therapy did not add benefit to standard chemotherapy after surgery. The HR for invasive DFS of 1.11 (95% CI, 0.87-1.42; P = .38), and consistent descriptive results for secondary efficacy end points do not support adding atezolizumab to adjuvant chemotherapy for patients who have undergone primary surgery for early-stage TNBC,” the study authors concluded. “Safety results were consistent with the known safety profile of atezolizumab in early-stage TNBC and across indications. Atezolizumab was associated with increased incidences of treatment-related grade 3 or 4 and serious adverse events, although more frequent visits during maintenance atezolizumab may bias comparison with chemotherapy alone. Atezolizumab did not compromise delivery of the standard chemotherapy backbone.”¹

References

1. Ignatiadis M, Bailey A, McArthur H, et al. Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial. JAMA. Published online January 30, 2025. doi:10.1001/jama.2024.26886

2. A Study Comparing Atezolizumab (Anti PD-L1 Antibody) In Combination With Adjuvant Anthracycline/​Taxane-Based Chemotherapy Versus Chemotherapy Alone In Patients With Operable Triple-Negative Breast Cancer (IMpassion030). ClinicalTrials.gov. Updated August 21, 2024. Accessed February 6, 2025. https://clinicaltrials.gov/study/NCT03498716

3. Drugs.com. Tecentriq FDA approval history. December 19, 2022. Accessed February 6, 2025. https://www.drugs.com/history/tecentriq.html