NSABP B-42 - "A Clinical Trial to Determine the Efficacy of Five Years of Letrozole Compared to Placebo in Patients Completing Five Years of Hormonal Therapy Consisting of an Aromatase Inhibitor (AI) or Tamoxifen Followed by an AI in Prolonging Disease-Free Survival in Postmenopausal Women with Hormone Receptor Positive Breast Cancer"

Treatment Plan    (Supplied Drug:  Letrozole/placebo)

Letrozole/placebo:  2.5mg, PO, QD, x 5 yrs

Pts should be evaluated for osteoporosis and fracture risks.  BMD required q 2 yrs while taking study drug.  See protocol for osteoporosis mgmt recommendations.

Eligibility

• Female pts only.

• ECOG perf status 0-1.

• Postmenopausal at regist.  No premenopausal or perimenopausal women requiring therapy w/LHRH analogs to suppress ovarian function.  See protocol for study's postmenopausal definition.

• Disease-free from time of initial breast cancer dx until randomiz.

• Must have had histol-confirmed invasive breast carcinoma by core needle bx or final path eval of the surgical specimen.

• Pts who received neoadjuv chemo must have been clin Stg I, II, or IIIA.  For pts who received adjuv, the prim tumor must have been T1-3 on path eval and ipsilateral nodes must have been pN0, pN1 (pN1mi, pNi1, pN1b, pN1c), pN2a, pN3a, or pN3b.

• Prim tumor must have been ER+ &/or PgR+ (pts considered borderline for hormone receptor positivity and who were treated w/Tamoxifen &/or AI are eligible).

• Must have undergone lumpectomy w/axillary nodal staging followed by breast RT or total mastectomy w/axillary nodal staging (acceptable axillary nodal staging includes SN bx alone, if sentinel nodes were negative on H&E staining).

• Duration of hormonal therapy following breast cancer dx must be 57-63 mos from 1st dose regardless of number of missed doses.  Hormonal therapy must be an AI or combination of <3 yrs Tamoxifen followed by AI.  No Tamoxifen during yrs 4 & 5 of adjuv hormonal therapy allowed.  NOTE:  Pts must discontinue adjuv AI therapy at regist. 

  See protocol for Optional Letrozole Regist Program for pts who have not yet completed 5 yrs of hormonal therapy.  During that time, Letrozole will be provided at no cost by Novartis.

• Randomiz w/i 6 mos following completion of 5 yrs (57-63 mos) of initial adjuv hormonal therapy.

• At time of randomiz:

  • H&P w/i 3 mos showing no recur breast cancer

  • Bilat mammogram w/i 1 yr (unilateral if mastectomy; mammogram not required if pt had prophylactic contralateral mastectomy)

  • BMD w/i 1 yr

  • Fasting lipid profile w/total cholesterol <grade 1 (CTCAE v3.0) w/ or w/o cholesterol-lowering therapy

    • w/i 1 yr if hx of hypercholesterolemia controlled w/cholesterol-lowering therapy &/or therapeutic lifestyle changes OR pt has hx of >1 of following:  diabetes, HTN, obesity, tobacco use, hypertriglyceridemia, documented CAD, or family hx of premature CHD.

    • w/i 2 yrs for all other pts

• No hx of non-traumatic osteoporotic fx of wrist, hip, or spine.

• No bilat breast cancer including DCIS (synchronous or metachronous).

• No other malignancies unless disease-free >5 yrs pre-randomiz and at low risk for recurrence (physician's opinion).  Following cancers are allowed if diagnosed and treated w/i past 5 yrs:  cervical or colon carcinoma or melanoma in situ, or non-melanoma skin cancer.

• No sex hormonal therapy (i.e., ER or PgR replacement therapy) or oral contraceptives, unless therapy DC'd pre-randomiz.

• No hormonal agent (i.e., Raloxifene) for mgmt of osteoporosis, unless therapy DC'd pre-randomiz.

• No investigational agent administered w/i 30 days pre-study entry.

• PRESTUDY REQUIREMENTS:

  • H&P, ht, wt (w/i 3 mos pre-randomiz)

  • Asmt of cardiac risk factors (w/i 3 mos pre-randomiz)

  • Fasting lipid panel (total chol, LDL-C, HDL-C, triglycerides) - w/i 1-2 yrs pre-randomiz*

  • Bilat mammogram (unilateral if mastectomy) - w/i 12 mos pre-randomiz

  • BMD testing (w/i 12 mos pre-randomiz)

  • Tumor block collection (w/i 3 mos after randomiz, w/pt's consent)

  *      Within 1 yr for pts w/hx of hypercholesterolemia or other risk factors for cardiovascular events or within 2 yrs for all other pts.

• Signed informed consent.