As reported in the Journal of Clinical Oncology by Sibylle Loibl, MD, PhD, and colleagues, the phase III PENELOPE-B trial has shown that palbociclib plus endocrine therapy did not improve invasive disease–free survival vs placebo plus endocrine therapy in patients with residual invasive hormone receptor (HR)-positive, HER2-negative breast cancer following neoadjuvant chemotherapy.
Study Details
The double-blind trial included 1,250 patients from sites in 11 countries without pathologic complete response after taxane-containing neoadjuvant chemotherapy at high risk of relapse (clinical pathologic staging–estrogen receptor grading score ≥ 3 or 2 and ypN1). They were randomly assigned between February 2014 and December 2017 to receive 13 cycles of palbociclib at 125 mg once daily or placebo on days 1 to 21 in 28-day cycles in addition to endocrine therapy. The primary endpoint was invasive disease–free survival.
Palbociclib for 1 year in addition to endocrine therapy did not improve invasive disease–free survival in women with residual invasive disease after neoadjuvant chemotherapy.— Sibylle Loibl, MD, PhD, and colleagues
Tweet this quote
Invasive Disease–Free Survival
Median follow-up was 42.8 months. At time of final analysis, confirmed invasive disease–free survival events occurred in 24.1% of patients in the palbociclib group vs 25.2% of the placebo group (stratified hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.74–1.17, P = .525). Most events were distant recurrence (76.3% vs 71.2%), followed by invasive locoregional recurrence (13.8% vs 17.3%). Estimated 3-year invasive disease–free survival was 81.2% vs 77.7%. Benefit of palbociclib was not identified in any subgroup evaluated.
Analysis excluding second primary invasive nonbreast cancers as an event showed a similar outcome (HR = 0.93, P = .501). Locoregional recurrence cumulative incidence rate at 3 years was 3.7% vs 4.6% (HR = 0.83, P = .514). Apparent benefit of palbociclib in locoregional recurrence was observed among the 200 patients with no response (stable or progressive disease) to neoadjuvant chemotherapy (HR = 0.20, P = .043).
Interim analysis of overall survival (after 131 deaths) showed no significant difference between groups (HR = 0.87, P = .420), with 3-year rates of 93.6% vs 90.5%.
Adverse Events
Grade 3 to 4 adverse events occurred in 79.6% of patients in the palbociclib group vs 20.1% of the placebo group, reflecting a higher incidence of hematologic events (73.1% vs 1.3%), including neutropenia (70.0% vs 1.0%) and leukopenia (56.1% vs 0.7%). The incidence of grade 3 to 4 nonhematologic events was similar in the two groups (19.9% v 19.0%). Nonhematologic adverse events of any grade that were more common with palbociclib were hypocalcemia (35.2% vs 24.4%), fatigue (66.4% vs 51.1%), stomatitis (27.5% vs 8.7%), constipation (22.1% vs 13.7%), cough (20.9% vs 16.2%), and infection (59.9% vs 51.1%); arthralgia (41.2% vs 46.8%) and hot flushes (43.8% vs 50.9%) were more common in the placebo group.
Overall, 3.0% of patients discontinued treatment due to toxicity. Eight fatal serious adverse events were reported, including two in the palbociclib group and six in the placebo group, with none considered related to treatment.
The investigators concluded, “Palbociclib for 1 year in addition to endocrine therapy did not improve invasive disease–free survival in women with residual invasive disease after neoadjuvant chemotherapy.”
Dr. Loibl, of the German Breast Group, c/o GBG Forschungs GmbH, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pfizer. For full disclosures of the study authors, visit ascopubs.org.
