Adding Ibrance in the Adjuvant Setting Does Not Improve Survival in Early-Stage Breast Cancer Subtype

The addition of Ibrance (palbociclib) to endocrine therapy in the adjuvant setting did not improve disease-free survival, compared with adjuvant endocrine therapy alone, in patients with hormone receptor (HR)-positive, HER2-negative, early-stage breast cancer, according to results from the PALLAS study’s planned second interim analysis.

Previous findings have shown that the addition of Ibrance to endocrine therapy improved progression-free survival, or the time from treatment to disease worsening, in women with metastatic HR-positive, HER2-negative breast cancer. Therefore, the researchers aimed to see if patients with early-stage disease would experience the same benefit to further reduce the risk of recurrence.

In the ongoing, multicenter, open-label, randomized, phase 3 study, the researchers compared the addition of two years of treatment with Ibrance to endocrine therapy in the adjuvant setting – which follows initial treatment, especially to prevent recurrence – compared with endocrine therapy alone in 5760 patients with stage 2 to 3 HR-positive, HER2-negative breast cancer.

The primary aim of the study was to evaluate disease-free survival, which is defined as the length of time after a patient’s primary treatment for their cancer ends that they survive without any signs or symptoms of their disease. Safety was also assessed.

At a median follow-up of 23.7 months, 170 of the 2,883 patients who were treated with Ibrance plus endocrine therapy experienced invasive disease-free survival events, while, of the 2,877 patients who received endocrine therapy alone, 181 had invasive disease-free survival events.

At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9–29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone

The most common grade 3 to 4 side effects in the Ibrance combination group, compared with endocrine therapy alone, included neutropenia (61.3% versus 0.3%, respectively), leucopenia (30.2% versus 0.1%) and fatigue (2.1% versus 0.3%). In addition, serious side effects occurred in more patients treated with the addition of Ibrance, compared with endocrine therapy alone (12.4% versus 7.6%, respectively).

In the Ibrance combination arm, 42% of patients stopped treatment prematurely, primarily because of side effects.

Of note, there were no treatment-related deaths.

To conclude, the researchers noted that the results could be explained by whether or not the drug duration or exposure, or both, were adequate. “A substantial proportion of patients in the palbociclib plus endocrine therapy group stopped palbociclib before two years, and lack of adequate exposure to palbociclib might have prevented an accurate evaluation of drug benefit,” the researchers wrote, adding that more ongoing exploratory analyses will fully characterize the impact of early discontinuation and variable exposure of Ibrance on efficacy outcomes.

“Additionally, analysis of patient-reported outcomes and adherence questionnaires will offer insight into the experience of receiving adjuvant palbociclib and impact on adherence to oral therapies.”

The PALLAS trial will continue to evaluate ongoing, long-term follow-up, as well as additional clinical and translational analyses in order to determine Ibrance’s exposure and effect in early-stage HR-positive, HER2-negative breast cancer.

“The PALLAS trial represents an important global collaboration between academia, community practice, and industry, rapidly achieving its desired target accrual to answer an important question about the management of breast cancer,” the researchers concluded. “The results of the PALLAS study remind us that benefits observed in the metastatic setting do not necessarily translate into the adjuvant setting, under- scoring the importance of doing well designed adjuvant trials to determine the potential efficacy of such therapies.”

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