Neoadjuvant Palbociclib Plus Letrozole in ER-Positive Early Breast Cancer: PALLET Trial

Lidia Schapira, MD


March 07, 2019

Randomized Phase II Study Evaluating Palbociclib in Addition to Letrozole as Neoadjuvant Therapy in Estrogen Receptor-Positive Early Breast Cancer: PALLET trial

Johnston S, Puhalla S, Wheatley D, et al
J Clin Oncol. 2019;37:178-189.

Study Summary

Palbociclib has been shown to be effective in treating metastatic breast cancer when used in combination with endocrine therapies. This study evaluated the effects of palbociclib plus letrozole as neoadjuvant therapy for postmenopausal women with estrogen receptor (ER)-positive breast cancer who were being treated with the intent for cure.

The study included 307 patients who were randomly assigned to treatment with letrozole alone for 14 weeks; letrozole for 2 weeks and then palbociclib plus letrozole to week 14; palbociclib for 2 weeks and then palbociclib plus letrozole to week 14; or palbociclib plus letrozole for 14 weeks.

The study had co-primary endpoints: change in Ki-67 from baseline to 14 weeks, and clinical response assessed by exam and ultrasound.

Clinical response was not significantly different between the groups, although measurements of Ki-67 favored palbociclib plus letrozole compared with letrozole alone, and this was accompanied by a reduction of apoptosis.

The investigators concluded that adding palbociclib to letrozole may not alter clinical response at 14 weeks but was found to enhance suppression of malignant proliferation in ER-positive breast cancer.


This report describes a phase 2 study of a CDK4/6 inhibitor given alone and in combination with letrozole in the neoadjuvant setting.

Although this will not change clinical practice, it provides interesting physiologic information about the effect of this class of drugs on previously untreated patients who present with early-stage breast cancer. Combination therapy induced a more pronounced suppression of Ki-67, and this is considered a better indicator of therapeutic activity than clinical response in ER-positive early breast cancer. Biomarker analysis suggests that the response to palbociclib was correlated with RB1 mutation status.

We will definitely learn more about the role of these agents from ongoing neoadjuvant and adjuvant trials and further analysis of tumor specimens.


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