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 (ClinicalTrials.gov 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.
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.
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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.
- 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