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A new immunotherapy schedule in addition to first-line hormone therapy for metastatic breast cancer patients in a state of clinical benefit during hormone therapy

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Abstract

Acquired resistance occurs in metastatic hormone receptor–positive breast cancer patients. The addition of interferon beta/interleukin-2 immunotherapy to first-line salvage hormone therapy (HT) prolonged progression-free (PFS) and overall survivals (OS) in 26 patients, as compared with 30 historical controls and literature data. This was a 2 : 1 ratio case–control retrospective observational study. The cases were from an open pilot study, started in 1992, and controls were recruited in 2006. The planned mean follow-up time was the time at which more than 80% of controls progressed. The median PFS was significantly longer in the cases than that in controls, 33.1 (95% CI 24.5–41.8) vs 18 (95% CI 12.1–23.8) months (p < 0.0001). Also, median OS was significantly longer in the cases, 81 vs 62 (95% CI 48.1–75.9) months (p < 0.0029). When analysis of the 2 groups was adjusted for the disease-free interval (DFI), hormone receptor status, HER2, site of metastases and molecular-targeted therapies, the hazard ratio for PFS and for OS in the cases increased from 2.347 to 3.090 and from 1.874 to 2.147, respectively. This occurred in spite of the higher proportion of controls (82% vs 7.1%) treated with aromatase inhibitors (AIs), while selective oestrogen receptor modulators (SERMs) were given to 92.9% of the cases and to 18% of the control group (p < 0.0001). Immunotherapy significantly prolonged PFS and OS during conventional first-line HT. A multi-centre randomised clinical trial is advised to enter this immunotherapy into clinical practice.

Key messages

• Acquired resistance occurs in metastatic endocrine-dependent breast cancer patients.

• Interferon beta-interleukin-2 immunotherapy added to first-line salvage hormone therapy prolonged progression-free (PFS) and overall (OS) survivals in 26 patients of a pilot study as compared with 30 historical controls.

• In this 2:1 ratio case–control prospective observational study, the PFS median time was significantly longer in the study group than that in controls, 33.1 (95% CI 24.5–41.8) vs 18 (95% CI 12.1–23.8) months (p < 0.0001).

• Also, the OS median time was significantly longer in the study group, 81 vs 62 (95% CI 48.1–75.9) months (p < 0.0029).

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Availability of data and material

All data used are available in the archive of the Department of Oncology, Oncologic Centre of Pisa University Hospital.

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Authors and Affiliations

  1. Department of Oncology, Transplantations and New Technologies in Medicine, University of Pisa, Pisa, Italy

    Andrea Nicolini & Paola Ferrari

  2. Epidemiology and Biostatistics Unit, Institute of Clinical Physiology,, National Research Council (CNR) and G. Monasterio Foundation, Pisa, Italy

    Giuseppe Rossi

  3. Statistics Section, University Hospital of Pisa, Pisa, Italy

    Riccardo Morganti

  4. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Angelo Carpi

Authors
  1. Andrea Nicolini
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  2. Giuseppe Rossi
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  3. Paola Ferrari
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  4. Riccardo Morganti
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  5. Angelo Carpi
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Contributions

All authors had full access to all data of the submitted study.

A. N. conceived the initial experimental design, conducted the study and wrote the manuscript; G. R. conceived the retrospective case–control observational study and carried out statistical analysis of previously published reports; P. F. conducted the study and revised the manuscript; R. M. carried out statistical analysis; A. C. conducted the study and revised the manuscript.

Corresponding author

Correspondence to Andrea Nicolini.

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Ethics approval and consent

All patients gave witnessed written informed consent and the study was approved by the Council of the Department of Internal Medicine of Pisa University. The study was performed in accordance with the Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Nicolini, A., Rossi, G., Ferrari, P. et al. A new immunotherapy schedule in addition to first-line hormone therapy for metastatic breast cancer patients in a state of clinical benefit during hormone therapy. J Mol Med 98, 375–382 (2020). https://doi.org/10.1007/s00109-020-01881-3

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  • DOI: https://doi.org/10.1007/s00109-020-01881-3

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