Palbociclib—a CDK 4/6 inhibitor—demonstrated significant efficacy in combination with the aromatase inhibitor letrozole in the first-line setting of estrogen receptor (ER)-positive, HER2-negative postmenopausal metastatic breast cancer, according to a study presented at the 2018 Miami Breast Cancer Conference (March 8-11, 2018).

Researchers analyzed the results form the phase III PALOMA-2 study. Across the full study, the combination of palbociclib plus letrozole significantly improved median progression-free survival (PFS) vs placebo plus letrozole in the first-line setting for metastatic disease.

The study enrolled 666 postmenopausal women from February 2013 to July 2014 and randomly assigned them (2:1) to receive palbociclib plus letrozole or placebo plus letrozole.

Researchers reported that the most common prior endocrine therapies received were tamoxifen, anastrozole, letrozole, and exemestane. The median average daily palbociclib dose was 125 mg across all subgroups.

Results from the study found that for patients with prior endocrine therapy, median PFS for the palbociclib-plus-letrozole group was 22.2 months vs 11.3 months for the placebo-plus-letrozole group. The objective response rate (ORR) was 33.7% vs 27%, respectively.

For patients with no prior endocrine therapy, the median PFS was 25.7 months in the palbociclib group vs 19.6 in the control group. The respective ORR rate was 52.8% and 44.8%.

Additionally, researchers reported that among those treated with prior chemotherapy, the median PFS was 22.4 months vs 13.7 months for those in the non-palbociclib group. The ORRs were 36.2% vs 30.3%, respectively. For patients with no prior chemotherapy, median PFS was 25.7 months vs 17 months in the palbociclib-plus letrozole group, with respective ORR rates of 47.6% vs 38.9%.

The most common treatment related adverse events were neutropenia, infections, leukopenia, nausea, fatigue, and arthralgia. Treatment emergent adverse events of any grade leading to permanent discontinuation occurred in less than 10% of patients, regardless of prior.

Investigators found that tolerability was consistent across the subgroups and in accord with the known safety profile of palbociclib when combined with endocrine therapy.—Janelle Bradley