Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer

To the Editor: In the PALOMA3 study, Turner et al. (July 16 issue)1 report that the addition of palbociclib to fulvestrant improved progression-free survival as compared with fulvestrant alone in patients with advanced breast cancer, with similar discontinuation rates because of adverse effects (2.6% and 1.7%, respectively). However, molecularly targeted therapies have moderate toxic effects that may become unacceptable over the long term and result in a deterioration in the quality of life, as shown in a previous report.2,3 The PALOMA1 study, a previous phase 2 trial of palbociclib with a median follow-up of approximately 30 months, showed that the combination of palbociclib and letrozole, as compared with letrozole alone, was associated with higher rates of discontinuation (11% vs. 2%) and dose interruption (33% vs. 4%) because of adverse effects.4 Furthermore, the rate of pulmonary embolism in the PALOMA1 study was higher than that in the PALOMA3 study (4% vs. 0.9%). Thus, because the authors report the results of a predetermined interim analysis with a median observation period of only 5.6 months, it is possible that further follow-up may reveal long-term toxic effects that disturb the regular administration of the combination therapy or hamper the use of subsequent therapies. Akihiko Ozaki, M.D. Minamisoma Municipal General Hospital Fukushima, Japan ozakiakihiko@gmail.com