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

Author(s): Jens Huober, MD1,2;Carlos H. Barrios, MD3;Naoki Niikura, MD, PhD4;Michał Jarząb, MD, PhD5;Yuan-Ching Chang, MD, PhD6;Shannon L. Huggins-Puhalla, MD7;José Pedrini, MD, PhD8;Lyudmila Zhukova, MD, PhD9;Vilma Graupner, PhD10;Daniel Eiger, MD10;Volkmar Henschel, PhD11;Nino Gochitashvili, MD, PhD12;Chiara Lambertini, PhD13;Eleonora Restuccia, MD10;and Hong Zhang, MD, PhD14;the IMpassion050 Trial Investigators
Source: DOI: 10.1200/JCO.21.02772 Journal of Clinical Oncology 40, no. 25
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

No soup for Atezolizumab on this one!  This expensive, six drug combination did not show any benefit in any subgroup.  Checkpoint inhibition does not seem to have any ground in neoadjuvant HER2+ breast cancer.

PURPOSE

Combining 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.

METHODS

Patients 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.

RESULTS

At 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.

CONCLUSION

Atezolizumab 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.

Author Affiliations

1Cantonal Hospital, Breast Center St Gallen, St Gallen, Switzerland;2University Hospital, Ulm, Germany;3Centro de Pesquisa em Oncologia, Hospital São Lucas, PUCRS, Porto Alegre, Brazil;4Department of Breast Oncology, Tokai University School of Medicine, Isehara, Japan;5Breast Cancer Unit, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland;6Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan;7UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA;8Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil;9SBIH Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM, Moscow, Russia;10Product Development Oncology, F. Hoffmann-La Roche Ltd, Basel, Switzerland;11Product Development Data Science, F. Hoffmann-La Roche Ltd, Basel, Switzerland;12Product Development Safety, Roche Products Limited, Welwyn Garden City, United Kingdom;13Oncology Biomarker Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland;14Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

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