Applying results to practice
“In luminal early breast cancer, the following patients – irrespective of their age – can safely be treated by endocrine therapy alone: patients with zero to three involved lymph nodes and recurrence score 0-11, and those with limited nodal burden (zero to two lymph nodes), recurrence score 12-25, and endocrine response after short preoperative endocrine therapy,” Dr. Harbeck summarized.
“Oncotype Dx testing can spare chemotherapy for the majority of patients with up to three involved lymph nodes. Dynamic Ki-67 response testing is feasible in clinical routine and complements baseline risk assessment to define patient selection for therapy deescalation or escalation,” she added.
The investigators have used the trial’s data to develop an algorithm for predicting the probability of response to short-course preoperative endocrine therapy that is available free of charge online (www.enrep.info).
“This may support everyday clinical decision-making in luminal early breast cancer; for example, whether to start a short period of preoperative endocrine therapy at all, and whether to rely on adjuvant endocrine therapy alone, but also in times like these, whether it’s safe to delay surgery by putting patients on prolonged preoperative endocrine therapy if surgical resources are scarce,” Dr. Harbeck commented.
Her clinic is now recruiting patients for the ADAPT Cycle trial, which is testing an endocrine-based approach with a CDK4/6 inhibitor versus chemotherapy in patients who are not candidates for adjuvant endocrine therapy alone. Therefore, all eligible patients receive the short course of endocrine therapy up front as the standard.
“But if you don’t have a trial, what are you going to do on Monday morning? Please let your patient know whether her tumor is endocrine responsive by doing this 3-week preoperative endocrine therapy,” Dr. Harbeck recommended. “It’s easy to do, you can schedule your surgeries better, and in patients with up to three lymph nodes, it helps with your decision-making, not just in the postmenopausal patients but also in the premenopausal patients, regarding whether they can forgo chemotherapy.”
Findings in context
More than 75% of ADAPT patients with RS 12-25 had a response to short-course endocrine therapy, noted invited discussant Lajos Pusztai, MD, DPhil, of the Yale Cancer Center in New Haven, Conn.
Dr. Lajos Pusztai
“This implies that the endocrine challenge is not informative for most patients,” he said, adding that a related question is whether the 25% of patients who did not have a response and were therefore given chemotherapy benefited from that therapy.
Dr. Pusztai cautioned that, among patients in the group with RS 12-25 who had a response to preoperative endocrine therapy, certain subgroups were fairly or very small: those aged 50 years or younger (330 patients) and those with two or three positive nodes (75 and 22 patients, respectively).
And collective findings of the similar but much larger TAILORx trial and RxPONDER trial (also reported at SABCS 2020) do suggest a benefit of chemotherapy in younger women, regardless of the number of positive nodes.
“Selection of [estrogen receptor]–positive patients with zero to three lymph nodes for adjuvant chemotherapy currently should be based on age and baseline recurrence score or a similar validated molecular assay,” Dr. Pusztai recommended. “TAILORx results guide us in regard to the use of the recurrence score in node-negative patients with a recurrence score of less than 26, and the recently presented RxPONDER results provide evidence for the use of recurrence score in patients with one to three positive nodes with a recurrence score in the range of 0-26. Both of these trials showed benefit in younger women from adjuvant chemotherapy.”
The ADAPT trial was sponsored by Roche, Genomic Health/Exact Sciences, Celgene, Bayer, Teva, and Amgen. Dr. Harbeck disclosed relationships with Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Merck, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Samsung, Sandoz, and Seattle Genetics. Dr. Pusztai disclosed relationships with AstraZeneca, Athenex, Almac, Bristol-Myers Squibb, Biotheranostics, Clovis, Daiichi, Eisai, Genentech, H2Bio, H3 Biomedicine, Immunomedics, Merck, Novartis, Pfizer, Pieris, Radius Health, Syndax, and Seattle Genetics,.