Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer
Open accessAbstract
BACKGROUND: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We report the results of a prespecified analysis of overall survival. METHODS: We randomly assigned patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety. RESULTS: Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib-fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo-fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16% of the patients in the placebo-fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib-fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo-fulvestrant group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib-fulvestrant group, as compared with 8.8 months in the placebo-fulvestrant group (hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up. CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib-fulvestrant resulted in longer overall survival than treatment with placebo-fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135 .).
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Consistent differences in outcomes (OS and IDFS) have emerged across phase III studies of CDK4/6 inhibitors.
“consistent differences in outcomes (OS and IDFS) have emerged across phase III studies of these therapies”
From Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3. (2024) · cites this paper as [21]
The Results report overall survival (OS) outcomes from the PALOMA-3 phase III trial, and the Discussion mentions OS data from other CDK4/6 inhibitor trials. But the Discussion says final OS data across trials were limited; it does not establish consistent differences across studies, and the paper does not report invasive disease-free survival (IDFS) outcomes. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPalbociclib, in contrast to abemaciclib and ribociclib, has not shown a clinically meaningful or statistically significant difference in OS in the first- or second-line ABC setting or an invasive disease-free survival (IDFS) benefit in the EBC setting.
“which in contrast to abemaciclib and ribociclib, has not shown a clinically meaningful or statistically significant difference in OS in the firstor second-line ABC setting or an invasive disease-free survival (IDFS) benefit in the EBC setting.17,18,21,22”
From Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3. (2024) · cites this paper as [21]
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Experimental — accuracy not yet measuredPALOMA-3 found a 19% lower death risk that was not deemed significant.
“The PALOMA-3 trial showed a 19% lower risk of death, which was”
From Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. (2022) · cites this paper as [30]
Palbociclib + fulvestrant failed to demonstrate a statistically significant overall survival benefit in the final prespecified or extended follow-up analysis of PALOMA-3.
“In PALOMA-3, palbociclib + fulvestrant failed to demonstrate a statistically significant OS benefit in the final prespecified (HR 0.81; 95% CI 0.64–1.03; P = 0.09) or extended follow-up analysis (HR 0.81; 95% CI 0.65–0.99) [11, 12].”
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“In PALOMA-3, palbociclib + fulvestrant did not demonstrate a statistically significant improvement in OS versus fulvestrant alone (HR 0.81; 95% CI 0.64–1.03; P = 0.09) in the final prespecified analysis or in an extended follow-up exploratory analysis (HR 0.81; 95% CI 0.65–0.99) [11, 12].”
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- Authors
- Turner, N. C., Slamon, D. J., Ro, J., Bondarenko, I., Im, S.-A., Masuda, N., Colleoni, M., DeMichele, A., Loi, S., Verma, S., Iwata, H., Harbeck, N., Loibl, S., André, F., Puyana Theall, K., Huang, X., Giorgetti, C., Huang Bartlett, C., & Cristofanilli, M.
- Affiliations
- Institute of Cancer Research (GB)
- University of California, Los Angeles (US)
- Seoul National University (KR)
- From the Institute of Cancer Research and Royal Marsden Hospital, London (N.C.T.); David Geffen School of Medicine at University of California, Los Angeles, Santa Monica (D.J.S.), and Pfizer Oncology, San Diego (X.H.) — both in California; National Cancer Center, Goyang-si, Gyeonggi-do (J.R.), and Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul (S.-A.I.) — both in South Korea; Dnipropetrovsk Medical Academy, City Multiple-Discipline...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-11-15
- Volume
- 379
- Issue
- 20
- Pages
- 1926-1936
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2896846857
- Cited by
- 1,276
- References
- 24
- Citations by year
- 2026: 98 · 2025: 168 · 2024: 153 · 2023: 183 · 2022: 183 · 2021: 201 · 2020: 171 · 2019: 106 · 2018: 11 · 2016: 1
- FWCI
- 92.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- palbociclib, fulvestrant, CDK4/6 inhibitors, hormone receptor-positive breast cancer, HER2-negative breast cancer, advanced breast cancer, overall survival, endocrine therapy sensitivity, visceral metastases, menopausal status, treatment safety, endocrine therapy resistance, progression-free survival, time to chemotherapy
- MeSH terms
- Fulvestrant, Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Double-Blind Method, Estradiol, Female, Humans, Middle Aged, Piperazines, Pyridines, Receptors, Steroid, Survival Analysis, Protein Kinase Inhibitors, ErbB Receptors
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