Article

Abemaciclib Plus Endocrine Therapy May Benefit Patients With Certain Characteristics

Patients with prognostic characteristics including higher-grade tumors, progesterone receptor (PgR)–negative tumors, liver metastases, and shorter treatment-free intervals derived a greater benefit from the addition of abemaciclib to endocrine therapy (ET) compared with ET alone, according to a recent study.

This story has been corrected to note that abemaciclib is an initial treatment for advanced breast cancer.

Patients with prognostic characteristics including higher-grade tumors, progesterone receptor (PgR)—negative tumors, liver metastases, and shorter treatment-free intervals derived a greater benefit from the addition of abemaciclib to endocrine therapy (ET) compared with ET alone, according to a recent study.

Treatment of hormone receptor—positive breast cancer with ET has been highly effective and well tolerated, though most patients will eventually progress. One approach to combating ET resistance has been the use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors with ET. CDK4/6 inhibitors such as abemaciclib in combination with ET as initial therapy and after ET progression have led to improved progression-free survival and objective response rates compared with ET alone.

Although the benefits of combination therapy tend to be greater than those of endocrine monotherapy, they are not universally applicable. In some patients, the benefits of endocrine monotherapy may be equivalent to those achieved with ET and abemaciclib, adding needless drug burden for these patients. Current treatment guidelines regarding this implication do not address which patients will benefit from combination therapy versus ET alone. In this analysis, prognostic characteristics were independently examined to determine subgroups who would derive the greatest benefits from abemaciclib and those who should receive endocrine monotherapy only.

Patients in the MONARCH 2 and MONARCH 3 trials were included for analysis. In the MONARCH 2 trial, patients who progressed after ET received fulvestrant with or without abemaciclib. In the MONARCH 3 trial, patients received a nonsteroidal aromatase inhibitor with or without abemaciclib as initial therapy for metastatic breast cancer.

In both trials, investigators found that the addition of abemaciclib provided the greatest benefit in patients with high-grade tumors, PgR-negative tumors, and liver metastases. Other poor prognostic factors, such as a higher Eastern Cooperative Oncology Group (ECOG) performance score and metastases in areas in addition to the bone, were also associated with significantly greater benefits. Factors such as age, presence of lung metastases, presence of pleural metastases, and prior neoadjuvant or adjuvant chemotherapy were found to not be significant prognostic factors.

In the MONARCH 3 trial, a longer treatment-free interval and time from diagnosis to recurrence represented better prognoses than did shorter periods for either interval. Investigators found that patients with shorter treatment-free intervals derived a greater benefit from adding abemaciclib to ET than patients with longer treatment-free intervals. Time from diagnosis to recurrence appeared to also be significantly prognostic, but it did not appear in an interpretable pattern, so it should not be used as a treatment indicator, according to investigators.

Although longer follow-up studies are needed, this analysis indicates that patients with more aggressive disease tend to benefit more from abemaciclib in combination with ET than ET alone, the researchers reported.

Reference

Di Leo AD, O’Shaunghnessy J, Sledge GW, et al. Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy. NPJ Breast Cancer. 2018;4(41). doi: 10.1038/s41523-018-0094-2.

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