Study: Avoid Completion ALND for Abemaciclib Eligibility in Early Breast Cancer

The use of completion axillary lymph node dissection (cALND) to determine the need for adjuvant abemaciclib (Verzenio) among women with luminal estrogen receptor (ER)-positive, HER2-negative early breast cancer should be discouraged, according to a post-hoc analysis of the phase III SENOMAC trial.

The prognostic procedure would need to be performed in 104 patients in order to avoid one invasive disease-free survival event at 5 years with the CDK4/6 inhibitor, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery, reported Jana de Boniface, MD, PhD, of Capio St. Göran’s Hospital in Stockholm, and colleagues.

After a median follow-up of 45.2 months among 1,342 patients, patient-reported severe or very severe impairment of physical arm function was reported in 13% of those who had undergone cALND compared with 4% of those who had sentinel lymph node biopsy only (χ² test P<0.0001).

“The high number of patients potentially developing severe arm morbidity after a cALND, among whom very few will have any oncological benefit as a result, clearly disqualifies this staging tool for the identification of candidates for adjuvant abemaciclib,” de Boniface and team wrote in Lancet Oncology.

In a commentary accompanying the study, Andrea V. Barrio, MD, of Memorial Sloan Kettering Cancer Center in New York City, noted that since arm morbidity was measured via patient-reported outcome measures and not volumetric measurements in this study, the morbidity associated with cALND “is probably underestimated in this trial.”

“Despite this limitation, the study findings show that use of cALND in this setting simply to eliminate uncertainty about abemaciclib candidacy is not justified due to an unfavorable risk-benefit ratio,” Barrio wrote. “Clinicians must return to making evidence-based systemic therapy decisions in the face of uncertainty regarding nodal status, and finally abandon ALND for patients with early-stage breast cancer once and for all.”

In luminal breast cancer, adjuvant CDK4/6 inhibitors such as abemaciclib improve invasive disease-free survival. The authors pointed out that for patients with T1-2, grade 1-2 tumors and one or two sentinel lymph node metastases, cALND is the only prognostic tool available that can reveal four or more nodal metastases (pN2-3) — the only indication for adjuvant abemaciclib in this setting.

The SENOMAC trial — which has a primary outcome of overall survival that has yet to be reported — previously showed that sentinel node biopsy only was noninferior to cALND in patients with clinically node-negative breast cancer who had sentinel-node macrometastases.

“Although adjuvant abemaciclib has become standard of care in high-risk luminal breast cancer, it has not yet shown an overall survival benefit,” de Boniface and team wrote. “And so, in light of these findings, which are in line with previous contributions to this clinical debate, we discourage the use of cALND in this setting.”

Patients included in the post-hoc analysis matched the eligibility criteria for cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have four or more nodal metastases.

In her commentary, Barrio noted that 19% of patients in the monarchE trial discontinued treatment with abemaciclib due to adverse events, “rendering any potential benefit of ALND obsolete in patients who are unable to complete treatment.”

“Another consideration is whether sentinel lymph node biopsy should be re-introduced in women aged 70 years and older, a practice that was largely abandoned after publication of CALGB 9343 to identify additional candidates for abemaciclib,” Barrio added.

The study was conducted across 67 centers in Sweden, Denmark, Germany, Greece, and Italy, and included a per-protocol population of 2,540 patients. For the post-hoc analysis, patients undergoing primary surgery for luminal, ER-positive, HER2-negative, T1-2, histological grade 1 or 2 breast cancer were selected from the per-protocol population.

Of these patients, 1,705 met the post-hoc analysis’ eligibility criteria, of whom 47% underwent cALND and 53% underwent a sentinel lymph node biopsy only. Median age at randomization was 62 years.

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