The Absolute Effect / Evidence / Breast Cancer
PENELOPE-B
Clinical question: Does adding one year of palbociclib to endocrine therapy improve outcomes after residual invasive HR-positive/HER2-negative disease following neoadjuvant chemotherapy?
Registry: NCT01864746 · One underlying study; follow-up publications consolidated.
Phase III · randomized · placebo-controlled · Evidence cut-off: 8 November 2026
Design, population and eligibility
International randomized double-blind phase III trial of one year of palbociclib after residual invasive disease following neoadjuvant chemotherapy.
1,250 randomized patients with high-risk HR-positive/HER2-negative residual disease.
HR-positive/HER2-negative early breast cancer with residual invasive disease after taxane-containing neoadjuvant chemotherapy and high-risk features.
Final survival analysis at median follow-up 77.8 months; six-year outcomes reported.
Treatment and comparator
Intervention: Palbociclib 125 mg orally days 1–21 of each 28-day cycle for 13 cycles, plus endocrine therapy.
Comparator: Placebo plus endocrine therapy.
Primary endpoint: Invasive disease-free survival (iDFS).
Key efficacy outcomes
6-year iDFS: 65.1% palbociclib vs 64.5% placebo HR 0.94 (95% CI 0.78–1.14); p=0.55.
6-year OS: 82.4% vs 80.3% HR 0.87 (95% CI 0.67–1.14); p=0.31.
Grade 3–4 adverse events: 79.6% vs 20.1% Predominantly haematological toxicity with palbociclib.
No improvement in iDFS or OS was demonstrated. At six years the iDFS absolute difference was +0.6 percentage points; HR 0.94, p=0.55.
Absolute outcome visualization
Six-year iDFS and overall survival.
Bars display source-reported rates; no rates are inferred from medians. Single-arm outcomes are not comparative effects.
NNT / NNH
No NNT: palbociclib did not significantly improve iDFS (HR 0.94; p=0.55).
The 59.5-point difference in grade 3–4 adverse events is clinically important, but the exact NNH should be calculated from the full trial safety population and endpoint definition; it is not derived here from summary percentages.
Toxicity, grade 3–5 harms and treatment burden
Grade 3–4 adverse events occurred in 79.6% with palbociclib versus 20.1% with placebo, mainly haematological. Treatment interruptions, dose reductions and discontinuations were more frequent with palbociclib; detailed event-specific grade 3–5 rates should be taken from the full safety tables.
13 cycles of 21 days on / 7 days off over approximately one year, with regular blood-count monitoring and dose holds/reductions for cytopenias.
Quality of life and patient-reported outcomes
No clinically meaningful QoL advantage is established. Additional monitoring and cytopenias add treatment burden without demonstrated efficacy benefit.
Subgroups and applicability
No discernible benefit across major prespecified subgroups in final survival analysis. Exploratory lobular histology signals are hypothesis-generating only.
Critical appraisal and limitations
Negative phase III study; selected high-risk post-neoadjuvant residual-disease population. Do not extrapolate the result to adjuvant ribociclib or abemaciclib trials, which have different populations and evidence.
Clinical interpretation
PENELOPE-B is important negative evidence: one year of palbociclib after residual disease did not improve iDFS or OS and substantially increased grade 3–4 toxicity.
Contemporary-practice note (8 November 2026): Historical trial results are separated from current practice. Comprehensive guideline-level freshness review remains pending for this batch; use current disease-specific guidance and multidisciplinary context.