Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study
Language English Country United States Media print-electronic
Document type Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
26371134
PubMed Central
PMC4737861
DOI
10.1200/jco.2015.61.5831
PII: JCO.2015.61.5831
Knihovny.cz E-resources
- MeSH
- Anastrozole MeSH
- Estrogen Receptor Antagonists administration & dosage MeSH
- Adult MeSH
- Estradiol administration & dosage analogs & derivatives MeSH
- Fulvestrant MeSH
- Antineoplastic Agents, Hormonal administration & dosage MeSH
- Aromatase Inhibitors administration & dosage MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Breast Neoplasms drug therapy pathology MeSH
- Nitriles administration & dosage MeSH
- Disease-Free Survival MeSH
- Drug Administration Schedule MeSH
- Aged MeSH
- Triazoles administration & dosage MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Anastrozole MeSH
- Estrogen Receptor Antagonists MeSH
- Estradiol MeSH
- Fulvestrant MeSH
- Antineoplastic Agents, Hormonal MeSH
- Aromatase Inhibitors MeSH
- Nitriles MeSH
- Triazoles MeSH
PURPOSE: To compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer. PATIENTS AND METHODS: The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor-positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring. RESULTS: In total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed. CONCLUSION: There are several limitations of this OS analysis, including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed, and that not all patients participated in additional OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast Cancer) trial (ClinicalTrials.gov identifier: NCT01602380).
See more in PubMed
Cardoso F, Costa A, Norton L, et al. ESO-ESMO 2nd International Consensus Guidelines for advanced breast cancer (ABC2) Ann Oncol. 2014;25:1871–1888. PubMed PMC
Cardoso F, Costa A, Norton L, et al. ESO-ESMO 2nd International Consensus Guidelines for advanced breast cancer (ABC2) Breast J. 2014;23:489–502. PubMed
Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J Clin Oncol. 2014;32:2255–2269. PubMed PMC
Ma CX, Reinert T, Chmielewska I, et al. Mechanisms of aromatase inhibitor resistance. Nat Rev Cancer. 2015;15:261–275. PubMed
Wakeling AE, Dukes M, Bowler J. A potent specific pure antiestrogen with clinical potential. Cancer Res. 1991;51:3867–3873. PubMed
Wakeling AE. Similarities and distinctions in the mode of action of different classes of antioestrogens. Endocr Relat Cancer. 2000;7:17–28. PubMed
Osborne CK, Wakeling A, Nicholson RI. Fulvestrant: An oestrogen receptor antagonist with a novel mechanism of action. Br J Cancer. 2004;90(suppl 1):S2–S6. PubMed PMC
Robertson JFR, Howell A, Gorbunova VA, et al. Sensitivity to further endocrine therapy is retained following progression on first-line fulvestrant. Breast Cancer Res Treat. 2005;92:169–174. PubMed
Osborne CK, Pippen J, Jones SE, et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: Results of a North American trial. J Clin Oncol. 2002;20:3386–3395. PubMed
Howell A, Robertson JFR, Quaresma Albano J, et al. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002;20:3396–3403. PubMed
Robertson JFR, Osborne CK, Howell A, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: A prospective combined analysis of two multicenter trials. Cancer. 2003;98:229–238. PubMed
Howell A, Robertson JFR, Abram P, et al. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: A multinational, double-blind, randomized trial. J Clin Oncol. 2004;22:1605–1613. PubMed
Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005;365:60–62. PubMed
Di Leo A, Jerusalem G, Petruzelka L, et al. Results of the CONFIRM Phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor–positive advanced breast cancer. J Clin Oncol. 2010;28:4594–4600. PubMed
Di Leo A, Jerusalem G, Petruzelka L, et al. Final overall survival: Fulvestrant 500mg vs 250mg in the randomized CONFIRM trial. J Natl Cancer Inst. 2014;106:djt337. PubMed PMC
Robertson JF, Llombart-Cussac A, Rolski J, et al. Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: Results from the FIRST study. J Clin Oncol. 2009;27:4530–4535. PubMed
Robertson JF, Lindemann J, Llombart-Cussac A, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: Follow-up analysis from the randomized ‘FIRST’ study. Breast Cancer Res Treat. 2012;136:503–511. PubMed
Nabholtz JM, Bonneterre J, Buzdar A, et al. Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: Survival analysis and updated safety results. Eur J Cancer. 2003;39:1684–1689. PubMed
Mehta RS, Barlow WE, Albain KS, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012;367:435–444. PubMed PMC
Mouridsen H, Gershanovich M, Sun Y, et al. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: Analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 2003;21:2101–2109. PubMed
Paridaens RJ, Dirix LY, Beex LV, et al. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: The European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol. 2008;26:4883–4890. PubMed PMC
Bergh J, Jönsson PE, Lidbrink EK, et al. FACT: An open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol. 2012;30:1919–1925. PubMed
Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor–positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): A randomised phase 2 study. Lancet Oncol. 2015;16:25–35. PubMed
Martin M, Loibl S, Von Minckwitz G, et al. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: The Letrozole/Fulvestrant and Avastin (LEA) study. J Clin Oncol. 2015;33:1045–1052. PubMed
Saad ED, Buyse M. Overall survival: Patient outcome, therapeutic objective, clinical trial end point, or public health measure? J Clin Oncol. 2012;30:1750–1754. PubMed
Turner NC, Ro J, Andre F, et al. Palbociclib in hormone receptor–positive advanced breast cancer. N Engl J Med. 2015 PubMed
Wardell SE, Ellis MJ, Alley HM, et al. Efficacy of SERD/SERM hybrid-CDK4/6 inhibitor combinations in models of endocrine therapy resistant breast cancer. Clin Cancer Res. 10.1158/1078-0432.CCR-15-0360 [epub ahead of print May 19, 2015] PubMed DOI PMC
ClinicalTrials.gov
NCT01602380
