The addition of atezolizumab to neoadjuvant chemotherapy generated numerical improvements in event-free survival, disease-free survival, and overall survival compared with chemotherapy plus placebo in patients with early-stage triple-negative breast cancer.
The addition of atezolizumab (Tecentriq) to neoadjuvant chemotherapy generated numerical improvements in event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) compared with chemotherapy plus placebo in patients with early-stage triple-negative breast cancer (TNBC), according to data from the final analysis of the phase 3 IMpassion031 trial (NCT03197935).1
Findings presented at the 2023 ESMO Breast Cancer Annual Congress showed that neoadjuvant atezolizumab plus chemotherapy generated an improvement in EFS vs chemotherapy alone (HR, 0.76; 95% CI, 0.47-1.21). Patients treated with the combination (n = 165) experienced 1- and 2-year EFS rates of 95% (95% CI, 92%-98%) and 85% (95% CI, 79%-90%), respectively. Those rates were 91% (95% CI, 86%-95%) and 80% (95% CI, 74%-86%), respectively, in patients given chemotherapy alone (n = 168).
Previously reported findings from IMpassion031 showed that neoadjuvant atezolizumab plus chemotherapy elicited a statistically significant improvement in pathologic complete response (pCR) rates vs chemotherapy alone. Patients in the atezolizumab arm experienced a pCR rate of 58% compared with 41% for those in the control arm, translating to a difference of 17% (95% CI, 6%-27%; 1-sided P = .0044).2
“pCR continues to be a prognostically favorable variable for long-term outcomes at individual patient levels,” presenting study author Carlos H. Barrios, MD, of the Latin American Cooperative Oncology Group and Hospital São Lucas in Brazil, said in the presentation of the data.
The international, randomized trial enrolled patients with untreated stage II/III TNBC who had a primary tumor greater than 2 cm and cT2 to cT4, cN0-cN3, or cM0 disease.1
Patients were randomly assigned 1:1. Those in the experimental arm received 840 mg of atezolizumab every 2 weeks plus 125mg/m2 of nab-paclitaxel (Abraxane) every week for 12 weeks, followed by 840 mg of atezolizumab plus 60 mg/m2 of doxorubicin and 600 mg/m2 of cyclophosphamide (ddAC) every 2 weeks for 8 weeks prior to surgery. Adjuvant atezolizumab was given at 1200 mg once every 3 weeks for 11 cycles.
Those in the control arm were given placebo plus nab-paclitaxel for 12 weeks, followed by placebo plus ddAC for 8 weeks. Patients were observed following surgery.
After surgery, patients in both arms were allowed to receive adjuvant systemic therapy if they did not achieve a pCR.
Patients were stratified by stage (II vs III) and PD-L1 status (<1% vs ≥1%). Along with the primary end point of pCR, secondary end points included EFS, OS, and DFS in the intent-to-treat and PD-L1–positive populations, as well as safety and patient-reported outcomes.
The median age of patients in the atezolizumab arm was 51 years (range, 22-76) compared with 51 years (range, 26-78) in the placebo arm. Most patients had an ECOG performance status of 0 (95% and 91% in the atezolizumab and placebo arms, respectively), were White (62% and 64%), had stage II disease (76% and 77%), were PD-L1 negative (53% and 55%), had a T2 primary tumor (70% and 73%), and had ductal histology (85% and 83%). Thirty-four percent and 43% of patients in the experimental arm and control arm, respectively, had positive regional lymph nodes.
At a median follow-up of 40.3 months in the atezolizumab arm and 39.4 months in the placebo arm, 155 patients in the atezolizumab arm proceeded to surgery and received adjuvant atezolizumab, compared with 153 patients in the placebo arm who had surgery and underwent observation.
Among 70 patients in the atezolizumab arm who did not achieve a pCR, 14 patients (20%) received adjuvant systemic therapy, which consisted of capecitabine (n = 4), other chemotherapy (n = 9), other targeted therapy (n = 1), or endocrine therapy (n = 1). In the 99 patients in the placebo arm who did not have a pCR, 33 patients (33%) received adjuvant systemic therapy that included capecitabine (n = 26), other chemotherapy (n = 5), other targeted therapy (n = 2), or endocrine therapy (n = 3).
Additional data showed that long-term outcomes favored the atezolizumab regimen vs the placebo regimen numerically for DFS (HR, 0.76; 0.44-1.30) and OS (HR, 0.56; 95% CI, 0.30-1.04). In the PD-L1–positive population, atezolizumab plus chemotherapy was also favored for DFS (HR, 0.57; 95% CI, 0.23-1.43) and OS (HR, 0.71; 95% CI, 0.26-0.91).
The 1- and 2-year DFS rates for the atezolizumab arm were 93% (95% CI, 89%-97%) and 87% (95% CI, 82%-93%), respectively, compared with a 1-year DFS rate of 90% (95% CI, 86%-95%) and a 2-year DFS rate of 83% (95% CI, 77%-89%) for the placebo arm.
In the atezolizumab arm, the 1-year OS rate was 99% (95% CI, 97%-100%), and the 2-year OS rate was 95% (95% CI, 91%-98%). In the placebo arm, the 1- and 2-year OS rates were 96% (95% CI, 93%-99%) and 90% (95% CI, 85%-95%), respectively.
No new safety signals or treatment-related deaths were reported with atezolizumab. Specifically for neoadjuvant therapy, grade 3/4 adverse effects (AEs) occurred in 63% and 60% of patients in the atezolizumab and placebo arms, respectively. Rates of grade 3/4 treatment-related AEs (TRAEs) were 57% and 53%, respectively. One patient in each arm experienced a grade 5 AE.
AEs leading to treatment discontinuation were reported in 23% of patients in the experimental arm and 20% of patients in the control arm. AEs leading to treatment discontinuation of atezolizumab or placebo occurred in 12% and 11% of patients, respectively.
Any-grade AEs of special interest were observed in 71% of patients in the atezolizumab arm, including 15% who had grade 3/4 events. Those rates were 60% and 12% in the placebo arm. Thirteen percent and 10% of patients required steroids in the experimental and control arms, respectively.
Regarding neoadjuvant and adjuvant treatment, grade 3/4 AEs were reported in 70% and 62% of patients in the control and experimental groups, respectively. Fifty-nine percent of patients in the atezolizumab arm had grade 3/4 TRAEs vs 54% in the placebo arm. One patient in the atezolizumab arm and 2 in the experimental arm had a grade 5 AE.
Twenty-five percent of patients in the experimental arm discontinued treatment, including 15% who discontinued atezolizumab. Twenty percent of patients in the placebo arm discontinued treatment, including 11% who discontinued placebo.
AEs of special interest occurred in 81% of patients in the atezolizumab arm, including 17% with grade 3/4 events, compared with 61% in the placebo arm, including 13% with grade 3/4 events. Sixteen percent and 10% of patients required steroids in the experimental and control arms, respectively.
An exploratory analysis showed that circulating tumor DNA (ctDNA) clearance was 89% at surgery in the atezolizumab arm, compared with 86% in the placebo arm. No patients who did not achieve ctDNA clearance had a pCR, compared with 50% of patients who did clear ctDNA. The pCR rates for patients who achieved ctDNA clearance were 62% in the experimental arm vs 41% in the control arm.
Positive ctDNA at surgery was associated with worse DFS (HR, 2.89; 95% CI, 220.127.116.11) and OS (HR, 3.08; 95% CI, 0.97-9.80). Additionally, OS favored the atezolizumab regimen in patients who did not achieve pCR and had ctDNA positivity (HR, 0.31; 95% CI, 0.03-2.67).
“[Patients who had] pCR and negative ctDNA had the best DFS and OS rates,” Barrios concluded.
Disclosures: Dr Barrios reported grants/research support to his institution from Nektar, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, GSK, Janssen, OBI Pharma, Lilly, Seagen, Roche, Bristol Myers Squibb, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda, TRIO, PharmaMar, Celgene, PPD, Syneos Health, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, Worldwide, Gilead Sciences, Bayer, and Servier; academic research projects with CPO, PUCRS, LACOG, and GBECAM; ownership or stock with Thummi and MEDSir; and advisory board or consulting roles with Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi, and Daiichi.
The study was sponsored by F Hoffmann-La Roche.