Palbociclib ( Ibrance ) is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6. In the randomized, open-label, phase II PALOMA-1/TRIO-18 trial, Palbociclib in combination with Letrozole ( Femara ) improved progression-free survival ( PFS ) compared with Letrozole alone as first-line treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer ( 20.2 months versus 10.2 months; hazard ratio, HR = 0.488, 95 % confidence interval ( CI ) 0.319-0.748; one-sided p = 0.0004 ).
Grade 3-4 neutropenia was the most common adverse event in the Palbociclib plus Letrozole arm.
Researchers have now presented efficacy and safety analyses based on several specific patient and tumor characteristics, and presented in detail the clinical patterns of neutropenia observed in the Palbociclib plus Letrozole arm of the overall safety population.
Postmenopausal women ( n = 165 ) with ER+, HER2-negative, advanced breast cancer who had not received any systemic treatment for their advanced disease were randomized 1:1 to receive either Palbociclib in combination with Letrozole or Letrozole alone.
Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death.
The primary endpoint was progression-free survival ( PFS ).
A clinically meaningful improvement in median progression-free survival and clinical benefit response ( CBR ) rate was seen with Palbociclib plus Letrozole in every subgroup evaluated.
Grade 3-4 neutropenia was the most common adverse effects with Palbociclib plus Letrozole in all subgroups.
Analysis of the frequency of neutropenia by grade during the first six cycles of treatment showed that there was a downward trend in grade 3-4 neutropenia over time.
Among those who experienced grade 3-4 neutropenia, 71.7 % had no overlapping infections of any grade and none had overlapping grade 3-4 infections.
In conclusion, the magnitude of clinical benefit seen with the addition of Palbociclib to Letrozole in improving both median progression-free survival and clinical benefit response rate is consistent in nearly all subgroups analyzed, and consistent with that seen in the overall study population.
The safety profile of the combination treatment in all subgroups was also comparable to that in the overall safety population of the study. ( Xagena )
Finn RS et al, Breast Cancer Res 2016;18:67. doi: 10.1186/s13058-016-0721-5