Breast Cancer

Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer—The Penelope-B Trial

Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer—The Penelope-B Trial

Background and Purpose


Patients with hormone receptor positive HerR-2/neu negative breast cancer, who underwent neoadjuvant chemotherapy, have a significant risk of having residual disease. This has a negative impact on long-term survival. This study was designed to determine the efficacy of 1 year of palbociclib, a cyclin-dependent kinase 4 / 6 inhibitor in the adjuvant setting along with an endocrine agent.

Patients of methods


PENELOPE-B is a double-blind, placebo controlled, phase 3 clinical trial in women with hormone receptor positive HER-2/neu negative primary breast cancer we did not achieve a pathologic complete response after taxane containing neoadjuvant chemotherapy or at high risk of relapse.  Clinical pathologic staging estrogen receptor grading score of at least 3 or 2 and ypN+.  Patients were randomized 1:1 to 1-13 cycles of palbociclib 125 mg once daily or placebo on days 1 through 21 and a 28-day cycle in addition to endocrine therapy. The primary endpoint was invasive disease-free survival. Final analysis was planned after 290 invasive disease-free survival events with a 2-sided efficacy boundary of P < 0.0463.

Results 

1,250 patients were randomly assigned.  The median age was 49 years old. The majority had positive residual disease in their lymph nodes. The Ki-67 was less than 15% for the majority of patients. 59.4% of patients had a clinical pathologic staging estrogen receptor grading score of at least 3. 50.1% received an aromatase inhibitor while 33% of premenopausal women received a luteinizing hormone releasing hormone analog in addition to either tamoxifen or an AI.  The median follow-up was 42.8 months, where 308 events were confirmed.  Palbociclib did not improve invasive disease-free survival versus placebo added to endocrine therapy, ET-stratified hazard ratio, 0.93 (95% CI, 0.74–1.17) and two-sided weighted log – rank test, P=0.525.  There was no difference among the subgroups.  Infection and vascular disorders were the most common serious adverse events, seen in 113 events, 9.1% of patients with no difference between the treatment arms.  There were 8 fatalities, 2 associated with palbociclib and 6 associated with placebo.

Conclusion

The authors concluded that 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.

https://ascopubs.org/doi/full/10.1200/JCO.20.03639

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