SC Trastuzumab Induces Immune Function in HER2+ Breast Cancer

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Trastuzumab administered subcutaneously delivered unique immunomodulation effects vs intravenous trastuzumab in patients with treatment-naive HER2-positive breast cancer.

Breast cancer: ©Science RF - stock.adobe.com

Breast cancer: ©Science RF - stock.adobe.com

Trastuzumab administered subcutaneously (SC) induced stromal tumor infiltrating lymphocyte (sTIL) enrichment, as well as favorably varied immune parameters in patients with HER2-positive breast cancer with residual disease after neoadjuvant treatment and had comparable efficacy to intravenous (IV) trastuzumab, according to a study published in the Journal for ImmunoTherapy of Cancer.1

A total of 63 patients were enrolled in the phase 2 study (NCT03144947) evaluating SC (n = 32) vs IV (n = 31) trastuzumab administration. In the IV trastuzumab arm, 20 of 31 (64.5%; 95% CI, 45.5%-80.1%) experienced a pathological complete response compared with 19 of 32 (59.4%; 95% CI, 40.1%-76.3%) patients in the SC trastuzumab arm. A relatively high rate (46%) of sTILs in post neoadjuvant residual tumors was seen in the SC administration arm compared with 27% in the IV administration arm.

Further, an upregulation of PD-1 on sTILs of residual disease and a decline of CD4-positive FoxP3-positive regulatory T cells was observed in the SC administration arm, while PD-L1 was upregulated in residual tumors in the IV administration arm. Both arms had significant CD8-positive T-cell increases in residual disease.

“In our patients, PD-L1 expression on pretreatment sTILs inversely correlated with CD3 expression on sTILs in residual disease after SC trastuzumab, thus suggesting that SC administration of trastuzumab may favor a shift towards T-cell mediated antitumor response,” study authors wrote.1

For safety, 23% and 33% of adverse events (AEs) were associated with pertuzumab (Perjeta) plus docetaxel with IV or SC trastuzumab, respectively. A total of 92% of all patients experienced AEs, with most being mild (grade 1 or 2).

The study enrolled patients with treatment-naive non-metastatic HER2-positive breast cancer. Patients needed to have an ECOG performance status ≤1, baseline left ventricular ejection fraction ≥55, and normal organ function.

Patients in the study received neoadjuvant IV 5-fluorouracil 500 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2 every 3 weeks for 3 cycles. Patients were then randomized to receive IV trastuzumab, pertuzumab, and docetaxel, or SC trastuzumab and IV pertuzumab and docetaxel every 3 weeks for 4 cycles. Patients underwent surgery 3 to 7 weeks after neoadjuvant therapy, and then patients received trastuzumab either IV or SC every 3 weeks for 14 cycles. Docetaxel dose modification was permitted, but dose modification was not allowed for pertuzumab or trastuzumab.

“A more mature follow-up is required to look for distinct prognostic significance of residual diseases bearing different immune profiles of TILs after either SC or intravenous neoadjuvant trastuzumab,” study authors wrote. “Based on our findings, novel immunotherapy strategies using [SC trastuzumab and pertuzumab] should be tested in clinical trials to achieve SC-specific, antitumor immune response.”

REFERENCE:
Pellegrino B, Tommasi C, Serra O, et al. Randomized, open-label, phase II, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with locally advanced, inflammatory, or early HER2-positive breast cancer-Immun-HER trial (GOIRC-01-2016). J Immunother Cancer. 2023;11(11):e007667. Published 2023 Nov 28. doi:10.1136/jitc-2023-007667
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