KEY TAKEAWAYS
- The phase III IMpassion050 study examined neoadjuvant atezolizumab PH and chemotherapy.
- The trial compared atezolizumab and placebo pCR rates in ITT and PD-L1-positive populations.
- Atezolizumab or placebo was given to patients with a primary tumor> 2 cm and positive lymph nodes.
- In ITT and PD-L1-positive patients, atezolizumab with dose-dense doxorubicin/cyclophosphamide-paclitaxel and PH did not improve pCR rates.
- However, atezolizumab had more grade 3-4 and serious adverse events than other combo studies.
- Atezolizumab’s long-term effects are unknown; however, PH and chemotherapy are still recommended for high-risk, HER2-positive early breast cancer.
Antitumor immunity, cytotoxic activity, and patient outcomes in high-risk, HER2-positive early breast cancer may be enhanced by combining standard of care (pertuzumab-trastuzumab [PH], chemotherapy) with cancer immunotherapy. The researchers present the primary analysis of neoadjuvant atezolizumab, phosphine hydrochloride, and chemotherapy in phase III IMpassion050. Patients with tumors> 2 centimeters in diameter and lymph node positivity (T2-4, N1-3, M0) were randomly assigned to receive either atezolizumab or placebo in combination with dose-dense doxorubicin/cyclophosphamide, then paclitaxel, and finally phosphamide (PH).
Patients were instructed to continue with atezolizumab/placebo and PH (total: 1 year of HER2-targeted therapy) following surgery, with the option to transition to ado-trastuzumab emtansine with atezolizumab/placebo for those who showed signs of residual illness. pathologic complete response (pCR) (ypT0/ypN0) and programmed cell death ligand 1 (PD-L1) positivity were the end goals of coprimary efficacy.
In the intent-to-treat populations, the pCR rates for placebo and atezolizumab 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 clinical cutoff date was February 5, 2021. 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). The incidence of adverse events in grades 3–4 and seriousness was higher in the atezolizumab group than in the placebo group. Atezolizumab was associated with five grade 5 adverse events (four neoadjuvant, one adjuvant, and two allocated to study treatment).
The safety profile was generally in line with what has been seen previously with atezolizumab in combo studies. In high-risk, HER2-positive early breast cancer, the addition of atezolizumab to neoadjuvant dose-dense doxorubicin/cyclophosphamide-paclitaxel and PH did not improve pCR rates compared to placebo in the intent-to-treat (ITT) or PD-L1-positive groups. Standard treatment for PH is still chemotherapy, but extended follow-ups may shed light on the drug’s long-term effects.
Source: https://pubmed.ncbi.nlm.nih.gov/35763704/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03726879
Jens Huober 1 2, Carlos H Barrios 3, Naoki Niikura 4, Michał Jarząb 5, Yuan-Ching Chang 6, Shannon L Huggins-Puhalla 7, José Pedrini 8, Lyudmila Zhukova 9, Vilma Graupner 10, Daniel Eiger 10, Volkmar Henschel 11, Nino Gochitashvili 12, Chiara Lambertini 13, Eleonora Restuccia 10, Hong Zhang
Huober J, Barrios C, Niikura N, Jarzab M, Chang Y, Puhalla S, Pedrini J, Zhukova L, Graupner V, Eiger D, Henschel V, Gochitashvili N, Lambertini C, Restuccia E & Zhang H. 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. 10.1200/JCO.21.02772.
