For patients with triple-negative breast cancer (TNBC), Tecentriq (atezolizumab) plus neoadjuvant chemotherapy followed by adjuvant Tecentriq did not significantly improve event-free survival (EFS), missing the primary end point of the phase 3 NSABP B-59/GBG-96-GeparDouze trial.
Results presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) showed that at a median follow-up of 46.9 months, the four-year EFS rate was 85.2% with Tecentriq plus chemotherapy versus 81.9% with placebo plus chemotherapy. This difference was not considered statistically significant, according to the researchers.
This lack of benefit was consistent across all patient subgroup except clinical nodal status, in which there was a significant difference favoring Tecentriq in patients with positive node status.
Glossary
Neoadjuvant: treatment given before surgery.
Adjuvant: treatment given after surgery.
Event-free survival (EFS): time without disease progression or relapse.
Primary end point: main goal measured at the end of a study to see if treatment worked.
Pathological complete response (pCR): no detectable cancer after treatment.
Disease-free survival: the time after treatment without cancer recurrence.
Overall survival (OS): time until death from any cause.
Distant disease-free survival: time without cancer spread to other organs.
Area under the curve: a measure of the drug concentration in the blood over time.
There was no overall survival (OS) benefit with Tecentriq at four years, with a rate of 90.2% versus 89.5% with placebo. The researchers noted that the addition Tecentriq to neoadjuvant chemotherapy boosted the pathological complete response (pCR) rate at 63% versus 57% with placebo.
“While not meeting efficacy criteria for the primary end point, the results support translational studies for potential biomarkers to identify subsets of patients with TNBC who may benefit from the addition of checkpoint inhibitors to neoadjuvant or adjuvant therapy,” said presenting author Dr. Charles Geyer from the University of Pittsburgh Medical Center.
The safety analysis for the trial included 1,532 of the 1,550 initially randomized patients. The results showed little difference between the two groups regarding rates of treatment-emergent side effects.
Across the entire safety population, nearly all patients experienced at least one treatment-emergent side effect, with 74.3% having grade 3 or 4 (severe or life-threatening) treatment-emergent side effects and 32.7% having serious treatment-emergent side effects.
Treatment-emergent side effects resulting in treatment discontinuation occurred at 12.1% versus 11.4% for paclitaxel in the Tecentriq versus chemotherapy arms, respectively; 8.5% versus 7.3%, respectively, for carboplatin; 5.2% versus 3.5%, respectively, for Adriamycin (doxorubicin) plus cyclophosphamide with epirubicin plus cyclophosphamide; and 21.2% versus 10.6%, respectively, for Tecentriq plus placebo. Treatment-emergent side effects were considered the cause of death for two patients in the Tecentriq group and three patients in the placebo group.
The trial enrolled 1,550 patients with TNBC. Across the whole population, the median age was 49 years and all patients except one were female. Forty-one percent of patients were node-positive, 59% had a primary tumor size between 1.1 and 3.0 centimeters (cm) and 41% had a primary tumor size greater than 3 cm. Sixty-four percent of patients were PD-L1 negative.
Ninety-five percent of patients had invasive ductal/invasive carcinoma of no special type, 81% of patients had grade 3 tumors. About half (52.8%) of patients had BRCA1/2 and PALB-2 wild-type. Specifically, 8.3% had a BRCA1 mutation, 2.5% had a BRCA2 mutation and 0.8% had a PALB-2 pathogenic variant.
Patients were randomized to Tecentriq or placebo with paclitaxel plus carboplatin, followed by investigator’s choice of cyclophosphamide with Adriamycin or epirubicin. After surgery, patients resumed Tecentriq at the same dose or placebo as adjuvant therapy for six months. Radiotherapy was administered with Tecentriq and placebo.
The primary end point of the trial was EFS, with secondary end points including OS, pCR in the breast and lymph nodes, distant disease-free survival, disease-free survival and toxicity.
Reference
“GS3-05: NSABP B-59/GBG-96-GeparDouze: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy with atezolizumab or placebo followed by adjuvant atezolizumab or placebo in patients with Stage II and III triple-negative breast cancer.” By Dr. Geyer C, et al. Presented at: San Antonio Breast Cancer Conference; December 10-14, 2024; Abstract GS3-05.
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