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, MD^1,2;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

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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