Adding palbociclib to letrozole significantly improved progression-free survival compared with letrozole alone among patients with previously untreated estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to findings published in The New England Journal of Medicine.1

The phase 2 PALOMA-1/TRIO-18 study demonstrated that progression-free survival was longer with the cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole than letrozole alone in the first-line treatment of postmenopausal women with ER-positive, HER2-negative advanced breast cancer. To confirm and expand the efficacy and safety data for this combination in this patient population, researchers designed the double-blind, phase 3 PALOMA-2 trial ( Identifier, NCT01740427).

Investigators enrolled 666 postmenopausal women with newly diagnosed ER-positive, HER2-negative breast cancer who had not received prior treatment for advanced disease. Participants were randomly assigned 2:1 to receive palbociclib in combination with letrozole or letrozole plus placebo.

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After a median follow-up of 23 months, researchers found that the combination of palbociclib and letrozole reduced the risk of progression or death by 42% (hazard ratio, 0.58; 95% CI, 0.46-0.72; P < .001) compared with letrozole alone; median progression-free survival was 24.8 months (95% CI, 22.1-not estimable) and 14.5 months (95% CI, 12.9-17.1), respectively.

The confirmed objective response rate among patients assigned to the palbociclib-letrozole group was 42.1% (95% CI, 37.5-46.9) overall vs 34.7% (95% CI, 28.4-41.3) in the letrozole arm. Among those with measurable disease, the confirmed objective response rate was 55.3% (95% CI, 49.9-60.7) with palbociclib-letrozole and 44.4% (95% CI, 36.9-52.2) with letrozole-placebo.

Patients in the palbociclib plus letrozole arm more frequently reported grade 3 or 4 neutropenia, leukopenia, anemia, and fatigue. Approximately 2% of patients experienced febrile neutropenia in the combination arm vs no patients in the letrozole arm.

RELATED: Breast Cancers With PIK3CA Mutations May Derive Greater Benefit From Letrozole

Findings from the PALOMA-2 trial confirmed the earlier results of PALOMA-1. Although the addition of palbociclib was associated with higher rates of myelotoxicity, investigators have been able to successfully manage these effects with appropriate supportive care and dose reductions.


  1. Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375:1925-36. doi: 10.1056/NEJMoa1607303