HER2 Support Group Forums - View Single Post

Rich66 · 10-31-2009, 01:33 PM

Breast Cancer Res Treat. 2005 Jul;92(2):169-74.
Sensitivity to further endocrine therapy is retained following progression on first-line fulvestrant.

Robertson JF, Howell A, Gorbunova VA, Watanabe T, Pienkowski T, Lichinitser MR.
Unit of Surgery, City Hospital, NG5 1PB, Nottingham, UK. John.Robertson@nottingham.ac.uk
There is a need for new endocrine agents that lack cross-resistance with currently available treatments to extend the endocrine treatment window and delay the need for cytotoxic chemotherapy. This retrospective analysis evaluated the response of postmenopausal patients with previously untreated metastatic/locally advanced breast cancer to further endocrine treatment following progression on first-line fulvestrant or tamoxifen. Patients received fulvestrant 250 mg (intramuscular injection every 28 days) plus matching tamoxifen placebo (once daily), or tamoxifen 20 mg (orally once daily) plus matching fulvestrant placebo (every 28 days) in a double-blind, randomized, phase III trial. Treatment continued until disease progression or withdrawal, when further endocrine therapy was initiated (at the treating physician's discretion). Information regarding subsequent therapies and responses was obtained by follow-up questionnaire. Two-hundred-and-forty-five questionnaires were returned (from 587 patients), 149 of which yielded follow-up data on patients receiving second-line endocrine therapy following fulvestrant (n=83) and tamoxifen (n=66). Second-line therapy produced objective responses (OR) in 6/44 (13.6%) and clinical benefit (CB) in 25/44 (56.8%) patients who had CB with fulvestrant and produced OR in 5/41 (12.2%) patients and CB in 27/41 (65.8%) patients who had CB with first-line tamoxifen. For patients deriving no CB from trial therapy, second-line therapy produced OR in 3/39 (7.7%) and CB in 15/39 (38.5%) patients in the fulvestrant group and OR in 4/25 (16.0%) and CB in 12/25 (48.0%) patients in the tamoxifen group. Results from this questionnaire-based study suggest that postmenopausal women with advanced breast cancer who respond to first-line fulvestrant or tamoxifen retain sensitivity to subsequent endocrine therapy.

PMID: 15986127 [PubMed - indexed for MEDLINE]

Breast Cancer Res Treat. 2003 May;79(2):207-11.
Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy.

Vergote I, Robertson JF, Kleeberg U, Burton G, Osborne CK, Mauriac L; Trial 0020 Investigators; Trial 0021 Investigators.
Department of Gynecologic Oncology, University Hospitals, Leuven, Belgium. Ignace.Vergote@uz.kuleuven.ac.be
PURPOSE: This retrospective evaluation of data from two randomized, multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy, usually tamoxifen, and on the estrogen receptor (ER) antagonist fulvestrant ('Faslodex'). PATIENTS AND METHODS: A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection. After progression on fulvestrant, some patients received another endocrine therapy. Responses to subsequent endocrine therapy were assessed using a questionnaire sent to the trial investigators. Best responses were classified as a complete or partial response (CR or PR), stable disease (SD) lasting > or = 24 weeks, or disease progression. RESULTS: Follow-up data were available for 54 patients who derived clinical benefit (CB, defined as CR, PR or SD) from fulvestrant and who received subsequent endocrine therapy, resulting in a PR in 4 patients, SD in 21 patients, and disease progression in 29 patients. Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy, resulting in a PR in 1 patient, SD in 17 patients, and disease progression in 33 patients. Aromatase inhibitors were used as subsequent endocrine therapy in > 80% of patients. CONCLUSIONS: After progression on fulvestrant, patients may retain sensitivity to other endocrine agents. Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women, and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required.

PMID: 12825855 [PubMed - indexed for MEDLINE]

Endocr Relat Cancer. 2006 Mar;13(1):251-5.
Endocrine response after prior treatment with fulvestrant in postmenopausal women with advanced breast cancer: experience from a single centre.

Cheung KL, Owers R, Robertson JF.
Division of Breast Surgery, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. kl.cheung@nottingham.ac.uk

FREE TEXT

The pure anti-oestrogen fulvestrant has now been licensed for use in advanced breast cancer which has progressed on an anti-oestrogen. Optimal sequencing of various endocrine agents becomes very important in the therapeutic strategy. We report our experience of further endocrine response with another endocrine agent after prior fulvestrant treatment. Among all patients with advanced breast cancer who had been entered into five phase II/III trials using fulvestrant as first- to ninth-line endocrine therapy in our Unit since 1993, 54 patients who fulfilled the following criteria were studied for their subsequent endocrine response: (i) oestrogen receptor positive or unknown; (ii) having been on a subsequent endocrine therapy for > or =6 months unless the disease progressed before; and (iii) with disease assessable for response according to International Union Against Cancer criteria. Eleven patients had received an aromatase inhibitor prior to fulvestrant, which resulted in five CBs (clinical benefit = objective remission/stable disease (SD)) for > or =6 months). Twenty-eight patients achieved CB on fulvestrant. They went on subsequent endocrine therapy with two partial responses, 11 SDs and 15 PDs (progressive disease) at 6 months. The median survival from starting fulvestrant and subsequent endocrine therapy was respectively 46.6 and 18.2 months. Among the remaining 26 patients who progressed at 6 months on fulvestrant, there were three SDs and 23 PDs at 6 months on subsequent endocrine therapy. The median survival from starting fulvestrant and subsequent endocrine therapy was respectively 12.5 and 9.3 months. Of all these 54 patients, 30% (n = 16) therefore achieved CB using another (second- to tenth-line) endocrine agent (anastrozole = 26; tamoxifen = 12; megestrol acetate = 11; others = 5). It would thus appear that further endocrine response can be induced in a reasonable proportion of patients after failing fulvestrant.

PMID: 16601292 [PubMed - indexed for MEDLINE]

10-31-2009, 01:33 PM	#4
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Fulvestrant+chemo synergy Breast Cancer Res Treat. 2005 Jul;92(2):169-74. Sensitivity to further endocrine therapy is retained following progression on first-line fulvestrant. Robertson JF, Howell A, Gorbunova VA, Watanabe T, Pienkowski T, Lichinitser MR. Unit of Surgery, City Hospital, NG5 1PB, Nottingham, UK. John.Robertson@nottingham.ac.uk There is a need for new endocrine agents that lack cross-resistance with currently available treatments to extend the endocrine treatment window and delay the need for cytotoxic chemotherapy. This retrospective analysis evaluated the response of postmenopausal patients with previously untreated metastatic/locally advanced breast cancer to further endocrine treatment following progression on first-line fulvestrant or tamoxifen. Patients received fulvestrant 250 mg (intramuscular injection every 28 days) plus matching tamoxifen placebo (once daily), or tamoxifen 20 mg (orally once daily) plus matching fulvestrant placebo (every 28 days) in a double-blind, randomized, phase III trial. Treatment continued until disease progression or withdrawal, when further endocrine therapy was initiated (at the treating physician's discretion). Information regarding subsequent therapies and responses was obtained by follow-up questionnaire. Two-hundred-and-forty-five questionnaires were returned (from 587 patients), 149 of which yielded follow-up data on patients receiving second-line endocrine therapy following fulvestrant (n=83) and tamoxifen (n=66). Second-line therapy produced objective responses (OR) in 6/44 (13.6%) and clinical benefit (CB) in 25/44 (56.8%) patients who had CB with fulvestrant and produced OR in 5/41 (12.2%) patients and CB in 27/41 (65.8%) patients who had CB with first-line tamoxifen. For patients deriving no CB from trial therapy, second-line therapy produced OR in 3/39 (7.7%) and CB in 15/39 (38.5%) patients in the fulvestrant group and OR in 4/25 (16.0%) and CB in 12/25 (48.0%) patients in the tamoxifen group. Results from this questionnaire-based study suggest that postmenopausal women with advanced breast cancer who respond to first-line fulvestrant or tamoxifen retain sensitivity to subsequent endocrine therapy. PMID: 15986127 [PubMed - indexed for MEDLINE] Breast Cancer Res Treat. 2003 May;79(2):207-11. Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy. Vergote I, Robertson JF, Kleeberg U, Burton G, Osborne CK, Mauriac L; Trial 0020 Investigators; Trial 0021 Investigators. Department of Gynecologic Oncology, University Hospitals, Leuven, Belgium. Ignace.Vergote@uz.kuleuven.ac.be PURPOSE: This retrospective evaluation of data from two randomized, multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy, usually tamoxifen, and on the estrogen receptor (ER) antagonist fulvestrant ('Faslodex'). PATIENTS AND METHODS: A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection. After progression on fulvestrant, some patients received another endocrine therapy. Responses to subsequent endocrine therapy were assessed using a questionnaire sent to the trial investigators. Best responses were classified as a complete or partial response (CR or PR), stable disease (SD) lasting > or = 24 weeks, or disease progression. RESULTS: Follow-up data were available for 54 patients who derived clinical benefit (CB, defined as CR, PR or SD) from fulvestrant and who received subsequent endocrine therapy, resulting in a PR in 4 patients, SD in 21 patients, and disease progression in 29 patients. Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy, resulting in a PR in 1 patient, SD in 17 patients, and disease progression in 33 patients. Aromatase inhibitors were used as subsequent endocrine therapy in > 80% of patients. CONCLUSIONS: After progression on fulvestrant, patients may retain sensitivity to other endocrine agents. Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women, and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required. PMID: 12825855 [PubMed - indexed for MEDLINE] Endocr Relat Cancer. 2006 Mar;13(1):251-5. Endocrine response after prior treatment with fulvestrant in postmenopausal women with advanced breast cancer: experience from a single centre. Cheung KL, Owers R, Robertson JF. Division of Breast Surgery, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. kl.cheung@nottingham.ac.uk FREE TEXT The pure anti-oestrogen fulvestrant has now been licensed for use in advanced breast cancer which has progressed on an anti-oestrogen. Optimal sequencing of various endocrine agents becomes very important in the therapeutic strategy. We report our experience of further endocrine response with another endocrine agent after prior fulvestrant treatment. Among all patients with advanced breast cancer who had been entered into five phase II/III trials using fulvestrant as first- to ninth-line endocrine therapy in our Unit since 1993, 54 patients who fulfilled the following criteria were studied for their subsequent endocrine response: (i) oestrogen receptor positive or unknown; (ii) having been on a subsequent endocrine therapy for > or =6 months unless the disease progressed before; and (iii) with disease assessable for response according to International Union Against Cancer criteria. Eleven patients had received an aromatase inhibitor prior to fulvestrant, which resulted in five CBs (clinical benefit = objective remission/stable disease (SD)) for > or =6 months). Twenty-eight patients achieved CB on fulvestrant. They went on subsequent endocrine therapy with two partial responses, 11 SDs and 15 PDs (progressive disease) at 6 months. The median survival from starting fulvestrant and subsequent endocrine therapy was respectively 46.6 and 18.2 months. Among the remaining 26 patients who progressed at 6 months on fulvestrant, there were three SDs and 23 PDs at 6 months on subsequent endocrine therapy. The median survival from starting fulvestrant and subsequent endocrine therapy was respectively 12.5 and 9.3 months. Of all these 54 patients, 30% (n = 16) therefore achieved CB using another (second- to tenth-line) endocrine agent (anastrozole = 26; tamoxifen = 12; megestrol acetate = 11; others = 5). It would thus appear that further endocrine response can be induced in a reasonable proportion of patients after failing fulvestrant. PMID: 16601292 [PubMed - indexed for MEDLINE] __________________ Mom's treatment history (link)