To fully evaluate hormone-blocking therapy following surgery for patients with early-stage high-risk HR+/HER2- breast cancer, researchers should continue to track patients for at least five years after the completion of active treatment, according to a study reported by Dana-Farber’s Meredith Regan, ScD.

The study also shows when planning post-surgical, or adjuvant, therapy for such patients, oncologists should carefully weigh the benefits and toxicities of available treatments, whether alone or in combination.

The study sought to clarify issues about the early, short-term effectiveness of drugs known as CDK4/6 inhibitors in adjuvant treatment of patients with high-risk hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer, after several clinical trials of such inhibitors in combination with endocrine therapy – drugs like tamoxifen or aromatase inhibitors, which deprive HR+ breast tumours of estrogen – have produced inconsistent early results and do not yet have long-term results available.

The monarchE trial found that combining the CDK4/6 inhibitor abemaciclib with endocrine therapy improved survival in the first two to three years after treatment, leading to abemaciclib’s approval for patients with early high-risk HR+/HER2- breast cancer.

While the Penelope-B trial also showed an early treatment effect for the CDK4/6 inhibitor palbociclib plus endocrine therapy, that benefit disappeared after about four years.

A third trial, dubbed PALLAS, found no survival benefit for palbociclib in combination with endocrine therapy.         

To gain some perspective on these findings, Regan and her colleagues drew on data from three earlier clinical trials – BIG 1-98, TEXT, and SOFT – that compared tamoxifen and aromatase inhibitors as adjuvant therapy for patients with non-metastatic breast cancer.

The trials, which collectively enrolled more than 10,000 patients, had reported results only after five years, leaving open the question of how the drugs performed in the short term, while also knowing the longer-term results.         

Because the trials included patients with both high- and low-risk breast cancer, researchers extracted data specifically on high-risk patients for comparison with the trials involving CDK4/6 inhibitors.

They focused on how these patients fared the first few years after treatment.           

They found that with two to three years of follow-up, the benefit of endocrine therapy in the BIG 1-98, SOFT, and TEXT trials was essentially the same as that of abemaciclib plus endocrine therapy in the monarchE study.

The three endocrine therapy studies showed that while the effects of treatment sometimes diminished over five years, rather than two years, they didn’t diminish nearly as much as they had over four years in the Penelope-B trial.         

By focusing on the years immediately following treatment in the endocrine therapy trials, researchers gained new insights into the risk of cancer recurrence during that period.

As expected, the trials showed that while the risk is relatively high in the short term, it declines steadily over the next five to ten years and persists at a low level. 

In each of the three trials, the pattern of risk over the first two to three years was somewhat different – something oncologists should be aware of when deciding on treatment plans with patients.

Source: Dana-Farber Cancer Institute