SABCS 2018: Comparing Letrozole With and Without Palbociclib in Metastatic Breast Cancer
Posted: Friday, December 14, 2018
Adding the targeted therapy palbociclib to letrozole suppressed malignant cell proliferation in patients with estrogen receptor–positive metastatic breast cancer, although it did not affect clinical response after 14 weeks. Stephen Johnston, MD, of The Royal Marsden NHS Foundation Trust, and colleagues presented the findings of the phase II PALLET trial at the 2018 San Antonio Breast Cancer Symposium (SABCS; Abstract GS3-02).
“We are hopeful, based on the results of this large trial, that combining this targeted therapy with hormone treatment may help to delay or even stop cancer coming back,” said Dr. Johnston in a press release from The Institute of Cancer Research. “This will require further research to confirm.”
The PALLET trial focused on postmenopausal women with estrogen receptor–positive primary breast cancer and tumors larger than 2 cm. The randomized trial recruited 307 patients, 279 of whom were evaluable at 14 weeks. Patients were randomly assigned to 1 of 4 treatment groups in a 3:2:2:2 ratio: 14 weeks of letrozole (group A); 2 weeks of letrozole followed by 14 weeks of letrozole plus palbociclib (group B); 2 weeks of palbociclib followed by 14 weeks of letrozole plus palbociclib (group C); and 14 weeks of letrozole plus palbociclib (group D). Group A was then compared with groups B, C, and D.
The co-primary endpoints were changes in expression of Ki67 protein, a marker of cell proliferation (measured by immunohistochemical staining), and clinical response (change in tumor size measured by ultrasonography). The Ki67 protein decreased significantly more in patients treated with letrozole plus palbociclib than in those treated with letrozole alone. A larger percentage of patients who received letrozole plus palbociclib achieved complete cell-cycle arrest (90%) compared with patients who received letrozole alone (59%).
Clinical response did not significantly differ among the groups. The authors speculated that this may have been because although adding palbociclib suppressed cell proliferation, it also reduced programmed cell death (apoptosis).
As for toxicity, in the groups treated with letrozole plus palbociclib, 50% of patients experienced a grade 3 or higher toxicity, compared with 17% in those who were treated with letrozole alone, mostly because of asymptomatic neutropenia.
