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Mammakarzinom: Biphosphonat-Therapie

allgemeines

  
EBCTCG - Metaanalyse(1) Fragestellung: Verbessern Biphosphonate das Ergebnis der adjuvanten Behandlung des Mammakarzinoms?
Antwort: Biphosphonate vermindern bei postmenopausalen Frauen die Rate von Knochenmetastasen und die Brustkrebsmortalität bei der adjuvanten Behandlung des Mammakarzinoms! Praemenopausale Frauen profitieren nicht von einer adjuvanten Biphosphonat - Therapie.
Kriterium alle nur PM
RR Statistik RR Statistik
Rezidiv 0,94 95% CI 0,87-1,01; 2p=0,08 0,86 95% CI 0,78-0,94; 2p=0,002
Metastasen 0,92 95% CI 0,85-0,99; 2p=0,03 0,82 95% CI 0,74-0,92; 2p=0,0003
Brustkrebs-Mortalität 0,91 95% CI 0,83-0,99; 2p=0,04 0,82 95% CI 0,73-0,93; 2p=0,002)
Knochen - Metastasen 0,83 95% CI 0,73-0,94; 2p=0,004 0,72 95% CI 0,60-0,86; 2p=0,0002
Frakturen 0,73 95% CI 0,94; 2p=0,004    
  • 18,766 Frauen mit Brustkrebs
  • 2-5 Jahre adjuvant Bisphosphonate
  • überwiegend Zoledronsäure und Clodronat
  • medianer Follow-up 5,6 Jahre
  • 3453 erste Rezidive
  • 2106 Sterbefälle
adjuvante Studien
Studie Patienten Tumor Chemotherapie Biphosphonat Dosis follow-up DFS (RR) OS (RR)
AZURE alle (4) 3360 Stadien II/III 95% Zoledronat 4 mg, 6x q3-4w, 8xq3m,5xq6m 60 Monate 0,98 (p=0,79) 1,01 (p=0,93)
AZURE: nur PM (4) 1101 Stadien II/III 95% Zoledronat 4 mg, 6 x q3-4w, 8xq3m,5xq6m 60 Monate 0,71 (p=0,0017) 0,71 (p=0,017)
ABCSG-12 (2) 1803 Prämenopausal <5% Zoledronat 4mg, 6xq6m 84 Monate 0,72 (p = 0,014) 0,63 (p = 0,0049)
ZOFAST (3) 1065 postmenopausal 0% Zoledronat 4 mg, 6xq6m 60 Monate 0,66 (p = 0,0375) n.s.
NSABP-B34 (7) 3323 Alle Stadien 65% Clodronat 1600 mg/d über 5 Jahre 101 Monate 0,91 (p=0,27) 0,84 (p=0,13)
Powles (6) 1069 Alle Stadien ? Clodronat 1600 mg/d über 2 Jahre 88 Monate 0,77 (p=0,127) 0,77 (p=0,047)
Diel (5) 302 Dis. Tumorzellen im KM 40% Clodronat 1600mg/d über 2 Jahre 103 Monate 0,98 (p=0,222) 0,83 (p=0,049)
Sarto 296 Nodal positive 90% Clodronat 1600 mg/d über 2 Jahre 98 Monate n.s. n.s.

Quellen

1.) Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Coleman R, et al.:
Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials.
Lancet 2015;386:1353-61. doi: 10.1016/S0140-6736(15)60908-4.

2.) Gnant M, Mlineritsch B, Schippinger W et al.:
Endocrine therapy plus zoledronic acid in premenopausal breast cancer.
N Engl J Med 2009; 360 (7): 679-691

3.) de Boer R, Bundred N, Eidtmann H et al.:
Long-Term survival Outcomes among Post­menopausal Women with Hormone Recep­tor-Positive Early Breast Cancer Receiving Adjuvant Letrozole and Zoledronic Acid: 5-Year Follow-Up of ZO-FAST.
Cancer Res 2011; 71

4.) Coleman RE, Marshall H, Cameron D et al.:
Breast-cancer adjuvant therapy with zoled­ronic acid.
N Engl J Med 2011; 365: 1396-1405

5.) Diel I, Jaschke A, Solomayer EF et al.:
Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the hone marrow: a longterm follow-up.
Ann Oncol 2008; 19: 2007-2011

6.) Powles T, Paterson S, Kanis JA et al.:
Rando­mized, placebo-controlled trial of clodrona­te in patients with primary operable breast cancer.
J Clin Oncol 2002; 20: 3219-3224

7.) Paterson AHG, Anderson SJ, Lembersky BC et al.:
NSABP Protocol B-34: A Clinical Trial Comparing Adjuvant clodronate vs. Placebo in Early Stage Breast Cancer patients Receiving Systemic Chemotherapy and / or Tamoxifen or No Therapy - Final Analysis.
Cancer Res 2011; 71

8.) Paterson AHG, Anderson SJ, Lembersky BC et al.:
Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial.
Lancet Oncol 2012;13:734-42. doi: 10.1016/S1470-2045(12)70226-7.

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Impressum                             Zuletzt geändert am 08.07.2024 11:56

Eur J Cancer. 2015 Dec 23;54:57-63. doi: 10.1016/j.ejca.2015.10.011. [Epub ahead of print] Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials. Kroep JR1, Charehbili A2, Coleman RE3, Aft RL4, Hasegawa Y5, Winter MC3, Weilbaecher K4, Akazawa K6, Hinsley S7, Putter H2, Liefers GJ2, Nortier JW2, Kohno N8. Author information Abstract PURPOSE: The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response. METHODS: Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (pCRb) and in the breast and lymph nodes (pCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC. RESULTS: pCRb and pCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase pCRb or pCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the pCRb rate (10.8% for CT only versus 17.7% with CT+ZA; odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01-4.55) and a non-significant benefit of the pCR rate (7.8% for CT only versus 14.6% with CT+ZA; OR 2.62, 95% CI 0.90-7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA. CONCLUSION: This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on pCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC.