The available evidence was insufficient to draw definitive conclusions about the effectiveness of prophylactic feeding tubes in the target patient population or to support an evidence-based practice guideline. After review of the evidence, of guidelines from other groups, and of current clinical practice in Canada, the multidisciplinary panel made consensus-based recommendations regarding comprehensive interdisciplinary clinical care before, during, and after cancer treatment. The recommendations are based on the expert opinion of the panel members and on their understanding of best clinical practice.

Background: Historically, androgens have been utilized for the treatment of BC as the androgen receptor (AR) is the most highly expressed steroid receptor (∼95% in estrogen receptor positive (ER+), ∼50% in ER negative). However, steroidal androgens often exhibit virilizing side effects, thus limiting clinical use. A non-steroidal, tissue-selective, AR modulator (SARM), GTx-024, offers a targeted approach of AR activation in ER+/AR+ BC without virilization or estrogenic effects. A previous Phase 2 study of 9 mg GTx-024 in MET ER+ BC demonstrated proof-of-concept, with 6/17 ER+/AR+ patients (pts) exhibiting clinical benefit (CB) following 6 months (m) of treatment. Increasing the dose to 18 mg has the potential for greater efficacy without compromising safety. Trial Design: Open label, multinational, randomized, parallel design Phase 2 study to assess the efficacy and safety of GTx-024 in PM ER+/AR+ BC. Pts will be randomized to receive GTx-024, 9 mg or 18 mg orally (PO) daily. Therapy continues until disease progression. Pts achieving a CB can be treated for 12 m following the initiation of study treatment; those demonstrating continued CB are offered continuation in a safety extension study under a separate protocol. Eligibility Criteria: Inclusion: Informed consent, female, ≥18 years (yr), PM, MET or LA ER+ (≥1% staining) BC, HER2 negative, ≥1 prior hormonal treatment for BC (≥6 m response for MET; ≥3 yr response for adjuvant), provide archived tumor tissue for AR determination, measurable or bone-only disease, evidence of PD within 30 days (d), ECOG 0 or 1. Exclusion: >1 prior chemotherapy regimen for MET, uncontrolled CNS metastases, radiotherapy ≤14d prior to enrollment, major surgery ≤28d prior to enrollment, currently receiving hormone replacement, hepatitis B/C positive, HIV positive, another active cancer. Specific Aims: Primary endpoint: proportion of AR+ pts in each arm achieving a CB response (CBR) at 24 weeks (wks). CBR defined as pts with a complete response (CR), partial response (PR), or stable disease (SD); per modified RECIST 1.1. Secondary endpoints: objective response rate, progression free survival, time to progression, and duration of response. Statistical Methods: Simon's two-stage (optimal) design will be used to assess primary efficacy, requiring up to 88 evaluable pts; i.e., pts with centrally confirmed AR+ who receive at least one dose of study drug. The trial will test for an unacceptably low CBR of ≤10% versus a CBR ≥30%. There is no intent to statistically compare the two dose arms, but to determine whether either or both doses result in an acceptable CBR. Target Accrual: Up to 118 pts will be enrolled. The first stage will be assessed in each arm among the first 18 evaluable pts. If at least 3/18 exhibit CB at 24 wks, then the arm will proceed to the second stage of recruitment up to a total of 44 pts. Otherwise, the arm will be discontinued for lack of efficacy. Trial Information: www.gtxinc.com Citation Format: Overmoyer B, Rugo H, Schwartzberg L, Palmieri C, Taylor R, Hancock M, Small S, Johnston MA. Phase 2 open label, multinational, randomized, parallel design study investigating the efficacy and safety of GTx-024 on metastatic (MET) or locally advanced (LA) ER+/AR+ breast cancer (BC) in postmenopausal (PM) women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-01-06.

Background: The androgen receptor (AR) is the most highly expressed steroid receptor in breast cancer (BC) with expression seen in up to 95% of estrogen receptor positive (ER+) and up to 50% of ER negative disease. Historically, steroidal androgens exhibited virilizing side effects, thus limiting clinical use. In TNBC, the expression of AR and androgen synthesizing enzymes is associated with lower proliferation, lower tumor grade, better overall survival, and more favorable clinical outcomes as compared to those patients with TNBC not expressing AR. Data from two trials targeting AR in TNBC indicates low level but encouraging clinical activity. A non-steroidal, tissue-selective, AR modulator (SARM), such as GTx-024, offers a targeted approach of AR activation in AR+ TNBC without virilization or estrogenic effects. Trial Design: Open label, multicenter, multinational, Phase 2 study for the treatment of advanced or metastatic TNBC. Subjects will receive GTx-024, 18 mg orally (PO) daily, continued until evidence of disease progression or toxicity. Subjects whose tumors demonstrate Clinical Benefit (CB) will be treated on study drug until progression. Eligibility Criteria: Inclusion: Female, ≥18 years old, confirmed AR+ (≥10% staining) TNBC (confirmed by medical history), up to 1-2 prior chemotherapy regimens, available archived tumor tissue, measurable or bone-only disease, ECOG 0 or 1, with prior toxicities from chemotherapy resolved. Exclusion: Life expectancy <4 months, uncontrolled CNS metastases, radiotherapy ≤14 days prior to enrollment, active hepatitis, HIV positive, prior treatment with anti-androgens, testosterone or testosterone-like agents, or estrogens or megesterol acetate, or prior treatment for a different cancer (other than BC or non-melanoma carcinoma of the skin) within the past 2 year Specific Aims: The primary aim is to measure the proportion of AR+ subjects with CB at 16 weeks; defined as subjects with a complete response (CR), partial response (PR), or stable disease (SD); per modified RECIST 1.1. Secondary endpoints include: objective response rate, progression free survival, and time to progression. Statistical Methods: Simon's two-stage (optimal) design will be used to assess primary efficacy, requiring up to 41 evaluable subjects; i.e., subjects with centrally confirmed AR+ who receive at least one dose of study drug. The first stage will be assessed among the first 21 evaluable subjects. If at least 2/21 achieve CB per modified RECIST 1.1 at 16 weeks, then the trial will proceed to the second stage of recruitment of up to a total of 41 subjects in the evaluable subset of the Full Analysis Set. Otherwise, the trial will be discontinued for lack of efficacy. The trial will test for an unacceptably low CBR of ≤5% versus a CBR more consistent with ≥20%. Target Accrual: Up to 55 subjects will be enrolled. Trial Information: www.gtxinc.com Citation Format: Rugo H, Overmoyer B, Schwartzberg L, Palmieri C, Taylor R, Hancock M, Small S, Johnston MA. A phase 2 open label, multi-center, multinational study investigating the efficacy and safety of GTx-024 on advanced, androgen receptor-positive triple negative breast cancer (AR+ TNBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-01-07.