# Palbociclib and Letrozole in Advanced Breast Cancer

Source: https://onco.cc/key-papers/paper-paloma-2-n-engl-j-med-2016/  
OnCo record `paper-paloma-2-n-engl-j-med-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the PALOMA-2 trial registered as NCT01740427, in New England Journal of Medicine (2016), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication.

Methods: In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety.

Results: The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group.

Conclusions: Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib combined with letrozole resulted in significantly longer progression-free survival than that with letrozole alone, although the rates of myelotoxic effects were higher with palbociclib-letrozole. (Funded by Pfizer; PALOMA-2 ClinicalTrials.gov number, NCT01740427.).

Indexed on Europe PMC as PubMed record 27959613 (DOI 10.1056/nejmoa1607303). Its abstract cites the registry id NCT01740427, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2016
- DOI: 10.1056/nejmoa1607303
- Authors: Finn RS, Martin M, Rugo HS, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT01740427 with the most citations, so it is the natural first reading for anyone following the PALOMA-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- N Engl J Med 2016: https://doi.org/10.1056/nejmoa1607303
- PubMed: https://pubmed.ncbi.nlm.nih.gov/27959613/
- Europe PMC: https://europepmc.org/article/MED/27959613
- ClinicalTrials.gov NCT01740427: https://clinicaltrials.gov/study/NCT01740427

## Connected records

- trials: [PALOMA-2](https://onco.cc/trials/paloma-2/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- ideas: [CDK4-selective inhibitors as the new first-line backbone](https://onco.cc/ideas/idea-cdk4-selective-first-line/)

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