Palbociclib Plus Letrozole Did Not Show Clinical Benefit in PALLET Trial
Addition of CDK4/6 inhibitor palbociclib to letrozole did not show clinical benefit, though it did enhance the suppression of malignant cell proliferation.
|The following article features coverage from the San Antonio Breast Cancer Symposium (SABCS) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
The addition of CDK4/6 inhibitor palbociclib to letrozole did not show clinical benefit as a neoadjuvant therapy for postmenopausal women with estrogen-receptor (ER)–positive primary breast cancer, though it did enhance the suppression of malignant cell proliferation (as assessed by Ki-67), according to results from the phase 2 PALLET trial (ClinicalTrials.gov Identifier: NCT02296801). The trial results were presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas, and published online in the Journal of Clinical Oncology.1,2
In the PALLET trial, 307 postmenopausal women with ER-positive primary breast cancer and tumors of at least 2.0 cm were recruited. Participants were randomized in a 3:2:2:2 fashion to 1 of 4 treatment arms. In arm A, patients received letrozole alone for 14 weeks. In arm B, patients received letrozole for 2 weeks followed by palbociclib plus letrozole to 14 weeks. In arm C, patients received palbociclib for 2 weeks followed by palbociclib plus letrozole to 14 weeks. In arm D, patients received palbociclib plus letrozole for 14 weeks.
The coprimary end points for letrozole (arm A) versus letrozole plus palbociclib (arms B, C, and D) were change in proliferation marker Ki-67 after 14 weeks and clinical response by ultrasound after 14 weeks.
Of the 307 patients recruited, 279 patients (90.8%) had a clinical response available and 190 patients (61.9%) had a paired Ki-67 available.
No significant difference was seen in objective response rate (complete response plus partial response) between those who received letrozole alone (arm A) and letrozole plus palbociclib (arms B, C, and D) (49.5% letrozole alone vs 54.4% letrozole combination; P = .20). The letrozole plus palbociclib arms had a greater median log-fold change in Ki-67 than the letrozole alone arm (4.1 vs 2.2; P < .0001). More patients who received letrozole combination had complete cell-cycle arrest than those who received letrozole alone (90% vs 59%; P < .001).
No new safety signals were observed.
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- Dowsett M, Jacobs S, Johnston S, et al. PALLET: A neoadjuvant study to compare the clinical and antiproliferative effects of letrozole with and without palbociclib. Oral presentation at: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Abstract GS3-02.
- Johnston S, Puhalla S, Wheatley D, et al. Randomized phase II study evaluating palbociclib in addition to letrozole as neoadjuvant therapy in estrogen receptor–positive early breast cancer: PALLET trial[published online December 6, 2018]. J Clin Oncol. doi: 10.1200/JCO.18.01624