medwireNews: The addition of palbociclib to adjuvant endocrine therapy does not prolong invasive disease-free survival (DFS) in hormone receptor-positive, HER2-negative, stage II–III breast cancer, shows the phase 3 PALLAS trial.
Reporting the results of the interim analysis at the ESMO Virtual Conference 2020, Erica Mayer (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) noted that “the benefits observed in the metastatic setting with palbociclib did not translate into the earlier adjuvant setting.”
Erica Mayer explains why the story of adjuvant palbociclib is not yet over despite the failure of the PALLAS study to meet its primary endpoint (2:42)
Indeed, the 3-year invasive DFS rates were comparable between the 2883 patients who were randomly assigned to receive the CDK4/6 inhibitor palbociclib 125 mg/day on a 3 weeks on and 1 week off schedule for 2 years with adjuvant endocrine therapy and the 2887 patients who received endocrine therapy alone, at 88.2% and 88.5%.
And after a median 23.7 months of follow-up, the 3-year distant recurrence-free survival was also similar between the palbociclib and control groups, at 89.3% and 90.7%, respectively.
Patients were enrolled in the study within 12 months of diagnosis and within 6 months of initiating adjuvant treatment; around 82% had stage IIB–III disease and a similar proportion had received prior chemotherapy. And 58.7% of patients had high clinical risk, meaning that they had at least four nodes involved or they had 1–3 nodes involved with T3–4 and/or histologic grade 3 disease.
Further analysis of subgroups did not find any particular subset of patients who derived benefit from the addition of palbociclib to endocrine therapy, including patients with high or low clinical risk. But Mayer emphasized that these analyses were limited by the small numbers of events.
She added that “no new toxicities were observed in patients receiving adjuvant palbociclib compared with the metastatic breast cancer setting,” with no treatment-related deaths. Nevertheless, more grade 3 or higher adverse events (AEs) occurred in the patients who received palbociclib plus endocrine therapy than endocrine therapy alone, at 72.4% versus 14.6%, the most common being neutropenia (61.3 vs 0.4%) and leukopenia (30.2 vs 0.1%).
In the combination arm, 42.2% of participants discontinued palbociclib early and 6.9% discontinued endocrine therapy early, and this was attributed to AEs in 64.2% and 14.3% of cases, respectively. By comparison, 6.3% of participants in the control arm discontinued endocrine therapy early, due to AEs in 12.5% of cases.
But “the PALLAS story does not end here,” stressed Mayer, and concluded that long-term follow-up “will continue for the PALLAS patient population at least for the next decade.”
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