Atezolizumab with neoadjuvant anti-human epidermal growth factor receptor 2 therapy and chemotherapy in human epidermal growth factor receptor 2-positive early breast cancer: Primary results of the randomized phase III IMpassion050 trial Journal Article
| Authors: | Huober, J.; Barrios, C. H.; Niikura, N.; Jarząb, M.; Chang, Y. C.; Huggins-Puhalla, S. L.; Pedrini, J.; Zhukova, L.; Graupner, V.; Eiger, D.; Henschel, V.; Gochitashvili, N.; Lambertini, C.; Restuccia, E.; Zhang, H.; the IMpassion050 Trial Investigators |
| Article Title: | Atezolizumab with neoadjuvant anti-human epidermal growth factor receptor 2 therapy and chemotherapy in human epidermal growth factor receptor 2-positive early breast cancer: Primary results of the randomized phase III IMpassion050 trial |
| Abstract: | PURPOSECombining standard of care (pertuzumab-trastuzumab [PH], chemotherapy) with cancer immunotherapy may potentiate antitumor immunity, cytotoxic activity, and patient outcomes in high-risk, human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We report the phase III IMpassion050 primary analysis of neoadjuvant atezolizumab, PH, and chemotherapy in these patients.METHODSPatients with a primary tumor of > 2 cm and histologically confirmed, positive lymph node status (T2-4, N1-3, M0) were randomly assigned 1:1 to atezolizumab/placebo with dose-dense doxorubicin/cyclophosphamide, followed by paclitaxel, and PH. After surgery, patients were to continue atezolizumab/placebo and PH (total: 1 year of HER2-targeted therapy); those with residual disease could switch to ado-trastuzumab emtansine with atezolizumab/placebo. Coprimary efficacy end points were pathologic complete response (pCR; ypT0/is ypN0) rates in intention-to-treat (ITT) and programmed cell death-ligand 1 (PD-L1)-positive populations.RESULTSAt clinical cutoff (February 5, 2021), pCR rates in the placebo and atezolizumab groups in the ITT populations were 62.7% (n = 143/228) and 62.4% (n = 141/226), respectively (difference -0.33%; 95% CI, -9.2 to 8.6; P =.9551). The pCR rates in the placebo and atezolizumab groups in patients with PD-L1-positive tumors were 72.5% (n = 79/109) and 64.2% (n = 70/109), respectively (difference -8.26%; 95% CI, -20.6 to 4.0; P =.1846). Grade 3-4 and serious adverse events were more frequent in the atezolizumab versus placebo group. Five grade 5 adverse events occurred (four neoadjuvant, one adjuvant; two assigned to study treatment), all with atezolizumab. Overall, the safety profile was consistent with that of atezolizumab in other combination studies.CONCLUSIONAtezolizumab with neoadjuvant dose-dense doxorubicin/cyclophosphamide-paclitaxel and PH for high-risk, HER2-positive early breast cancer did not increase pCR rates versus placebo in the ITT or PD-L1-positive populations. PH and chemotherapy remains standard of care; longer follow-up may help to inform the long-term impact of atezolizumab. © American Society of Clinical Oncology. |
| Keywords: | adult; cancer chemotherapy; controlled study; treatment outcome; treatment response; aged; middle aged; cancer surgery; primary tumor; major clinical study; clinical trial; fatigue; histopathology; hepatitis; doxorubicin; placebo; cancer growth; drug efficacy; drug safety; side effect; paclitaxel; cancer patient; neoadjuvant therapy; cancer staging; outcome assessment; follow up; antineoplastic agent; metabolism; multiple cycle treatment; randomized controlled trial; vomiting; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; cyclophosphamide; pathology; breast neoplasms; monoclonal antibody; asthenia; loading drug dose; rash; alanine aminotransferase; aspartate aminotransferase; minimal residual disease; breast tumor; lymph node; cancer size; sepsis; receptor, erbb-2; phase 3 clinical trial; hyperthyroidism; hypothyroidism; trastuzumab; pertuzumab; programmed death 1 ligand 1; surgical patient; molecularly targeted therapy; adverse event; clinical outcome; septic shock; demographics; trastuzumab emtansine; lung alveolitis; antibodies, monoclonal, humanized; human epidermal growth factor receptor 2 positive breast cancer; dose densification; very elderly; humans; human; male; female; article; atezolizumab; b7-h1 antigen; alanine aminotransferase level; aspartate aminotransferase level; coronavirus disease 2019 |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 40 |
| Issue: | 25 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2022-09-01 |
| Start Page: | 2946 |
| End Page: | 2956 |
| Language: | English |
| DOI: | 10.1200/jco.21.02772 |
| PUBMED: | 35763704 |
| PROVIDER: | scopus |
| PMCID: | PMC9426828 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2022 -- Source: Scopus |
