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Breast cancer

PALOMA-3 confirms that CDK4/6 is a key therapeutic target

Nature Reviews Clinical Oncology volume 12, page 436 (2015)Cite this article

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Activation of cyclin-dependent kinases 4 and 6 (CDK4/6)—key proteins that upon binding to cyclin D1, promote cell-cycle entry—seems to drive proliferation of breast cancer cells in hormone-receptor positive (HR+) disease. Now, the initial results of the PALOMA-3 trial confirm that the CDK4/6 inhibitor palbociclib, in combination with hormonal therapy, is an effective treatment option for women with HR+ metastatic breast cancer that had progressed on prior endocrine therapy.

Nicholas Turner, lead author of the study, explains the rationale of PALOMA-3, “prior research with derived endocrine-resistant cell lines has suggested that as breast cancers become resistant to endocrine therapy, they remain dependent on CDK4/6.” Furthermore, palbociclib, a highly specific CDK4/6 inhibitor, is able to induce responses in HR+ tumours and has a synergistic effect when combined with endocrine therapy, such as fulvestrant. Thus, in this double-blinded phase III trial, the investigators randomized 521 patients with HR+ and HER2-negative advanced-stage breast cancer that had relapsed or progressed during prior endocrine therapy to receive fulvestrant in combination with palbociclib or placebo in a 2:1 ratio.

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References

  1. Turner, N. et al. Palbociclib in hormone-receptor–positive advanced breast cancer. N. Engl. J. Med. 10.1056/NEJMoa1505270

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  1. Alessia Errico
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Errico, A. PALOMA-3 confirms that CDK4/6 is a key therapeutic target. Nat Rev Clin Oncol 12, 436 (2015). https://doi.org/10.1038/nrclinonc.2015.113

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