KEY TAKEAWAYS
- The PALOMA-4 trial compared palbociclib with letrozole to placebo plus letrozole in postmenopausal Asian women.
- The method involved randomizing 340 patients to palbociclib plus letrozol or placebo plus letrozole.
- The most common AEs with palbociclib plus letrozole were neutropenia, leukopenia, thrombocytopenia, anemia, and grade 3/4 neutropenia.
- Palbociclib and letrozole are recommended as first-line treatment for postmenopausal Asian women with ER+/HER2- ABC.
Women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) have shown efficacy and a manageable safety profile with the cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with endocrine therapy in international phase 3 trials. Palbociclib plus letrozole was compared to placebo plus letrozole for effectiveness and safety in Asian women with ER+/HER2- ABC in a phase 3 experiment called PALOMA-4. The study randomized (n = 340) postmenopausal women who had never received any systemic treatment for advanced illness to receive either palbociclib (125 mg/d orally; 3 weeks on, 1 week off) with 2.5 mg/d of letrozole or placebo plus letrozole (orally; continuously). The primary endpoint was progression-free survival (PFS), as measured by the investigators. Both tumor response and safety were measured but not prioritized.
Compared to placebo plus letrozole, the median PFS for those who received palbociclib and letrozole was 21.5 months (95% CI, 16.6-24.9 months) (hazard ratio, 0.68 [95% CI, 0.53-0.87]; P = 0.0012). Neutropenia, leukopenia, thrombocytopenia, and anemia were the most prevalent adverse events (AEs) with palbociclib plus letrozole, which aligns with the known safety profile. Those receiving palbociclib were less likely to experience neutropenia of any grade than those receiving a placebo (1.2% vs 84.5%). In the palbociclib group, there was one severe adverse event (AE), febrile neutropenia. The results of PALOMA-4 show that first-line palbociclib plus letrozole is effective and safe for postmenopausal Asian women with ER+/HER2- ABC. The combination of palbociclib and letrozole has not been linked to any new safety concerns.
Source: https://pubmed.ncbi.nlm.nih.gov/36155117/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02297438
Xu B, Hu X, Li W, Sun T, Shen K, Wang S, Cheng Y, Zhang Q, Cui S, Tong Z, Geng C, Song E, Huang CS, Sriuranpong V, Ngan RKC, Chia YH, Wang X, Zhao H. Palbociclib plus letrozole versus placebo plus letrozole in Asian postmenopausal women with oestrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Primary results from PALOMA-4. Eur J Cancer. 2022 Nov;175:236-245. doi: 10.1016/j.ejca.2022.08.012. Epub 2022 Sep 22. PMID: 36155117.
