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Study Offers Guidance for Future Trials of Adjuvant Therapy for Early-Stage Hormone Receptor–Positive/HER2-Negative Breast Cancer


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To fully evaluate hormone-blocking therapy following surgery for patients with early-stage high-risk hormone receptor–positive/HER2-negative breast cancer, researchers should continue to track patients for at least 5 years after the completion of active treatment, according to a study reported at the 2022 ASCO Annual Meeting by Regan et al (Abstract 508). The study also showed that when planning 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 cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in the adjuvant treatment of patients with high-risk hormone receptor–positive/HER2-negative breast cancer. Several clinical trials of such inhibitors in combination with endocrine therapy have produced inconsistent early findings 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 2 to 3 years after treatment, leading to abemaciclib’s approval for patients with early-stage high-risk hormone receptor–positive/HER2-negative breast cancer. Although the Penelope-B trial also showed an early treatment effect with the CDK4/6 inhibitor palbociclib plus endocrine therapy, that benefit disappeared after about 4 years. A third trial, PALLAS, found no survival benefit for palbociclib in combination with endocrine therapy.

To gain some perspective on these findings, Meredith Regan, ScD, of the Dana-Farber Cancer Institute, and 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 nonmetastatic breast cancer. The trials, which collectively enrolled more than 10,000 patients, had reported results after 5 years, leaving open the question of how the drugs performed in the short term.          

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 2 to 3 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 although the effects of treatment sometimes diminished over 5 years, rather than 2 years, they didn’t diminish nearly as much as they had over 4 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 although the risk is relatively high in the short term, it declines steadily over the next 5 to 10 years and persists at a low level. In each of the three trials, the pattern of risk over the first 2 to 3 years was somewhat different—something oncologists should be aware of when deciding on treatment plans with patients. 

Disclosures: For full disclosures of the study authors, visit coi.asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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