Mammalian target of rapamycin (mTOR) inhibitor therapy plus endocrine therapy

The Breast Cancer Trial of Oral Everolimus (BOLERO-2 [NCT00863655]) was a randomized, phase III, placebo-controlled trial in which patients with hormone receptor–positive metastatic breast cancer that is resistant to nonsteroidal aromatase inhibition were randomly assigned to receive either the mTOR inhibitor everolimus plus exemestane, or placebo plus exemestane.[27][Level of evidence B1]

The Breast Cancer Trial of Oral Everolimus (BOLERO-2 [NCT00863655]) was a randomized, phase III, placebo-controlled trial in which patients with hormone receptor–positive metastatic breast cancer that is resistant to nonsteroidal aromatase inhibition were randomly assigned to receive either the mTOR inhibitor everolimus plus exemestane, or placebo plus exemestane.[27][Level of evidence B1]

At the interim analysis, median PFS was 6.9 months for everolimus plus exemestane and 2.8 months for placebo plus exemestane (HR, 0.43; 95% CI, 0.35–0.54; P < .001).

The Breast Cancer Trial of Oral Everolimus (BOLERO-2 [NCT00863655]) was a randomized, phase III, placebo-controlled trial in which patients with hormone receptor–positive metastatic breast cancer that is resistant to nonsteroidal aromatase inhibition were randomly assigned to receive either the mTOR inhibitor everolimus plus exemestane, or placebo plus exemestane.[27][Level of evidence B1]

The addition of everolimus to exemestane was more toxic than was placebo plus exemestane, with the most-common grade 3 or 4 adverse events being stomatitis (8% vs. 1%), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%).

The Breast Cancer Trial of Oral Everolimus (BOLERO-2 [NCT00863655]) was a randomized, phase III, placebo-controlled trial in which patients with hormone receptor–positive metastatic breast cancer that is resistant to nonsteroidal aromatase inhibition were randomly assigned to receive either the mTOR inhibitor everolimus plus exemestane, or placebo plus exemestane.[27][Level of evidence B1]

OS differences were not significant after further follow-up.[28]

TAMRAD (NCT01298713) was an open-label, randomized, phase II trial comparing tamoxifen with tamoxifen plus everolimus in postmenopausal women whose disease had progressed after receiving an AI in the adjuvant or metastatic setting. The trial randomly assigned 57 women to receive tamoxifen and 54 women to receive the combination therapy.[29]

TAMRAD (NCT01298713) was an open-label, randomized, phase II trial comparing tamoxifen with tamoxifen plus everolimus in postmenopausal women whose disease had progressed after receiving an AI in the adjuvant or metastatic setting. The trial randomly assigned 57 women to receive tamoxifen and 54 women to receive the combination therapy.[29]

Median time to progression was 8.6 months in the combination group and 4.5 months in the tamoxifen group (HR, 0.54; 95% CI, 0.56−0.81; P = .002).

TAMRAD (NCT01298713) was an open-label, randomized, phase II trial comparing tamoxifen with tamoxifen plus everolimus in postmenopausal women whose disease had progressed after receiving an AI in the adjuvant or metastatic setting. The trial randomly assigned 57 women to receive tamoxifen and 54 women to receive the combination therapy.[29]

Toxicities were greater on the everolimus arm and similar to those in the BOLERO2 trial.

TAMRAD (NCT01298713) was an open-label, randomized, phase II trial comparing tamoxifen with tamoxifen plus everolimus in postmenopausal women whose disease had progressed after receiving an AI in the adjuvant or metastatic setting. The trial randomly assigned 57 women to receive tamoxifen and 54 women to receive the combination therapy.[29]

In an exploratory analysis, OS was 32.9 months in the tamoxifen group and not reached in the combination group (HR, 0.45; 95% CI, 0.24−0.81; P = .007).[29][Level of evidence A1]

PrE0102 (NCT01797120) was a double-blind, randomized, phase II trial comparing fulvestrant with fulvestrant plus everolimus in postmenopausal women whose disease had progressed after receiving an AI in the adjuvant or metastatic setting. Sixty-six women were randomly assigned to the combination arm and 65 to fulvestrant alone.[30]

PrE0102 (NCT01797120) was a double-blind, randomized, phase II trial comparing fulvestrant with fulvestrant plus everolimus in postmenopausal women whose disease had progressed after receiving an AI in the adjuvant or metastatic setting. Sixty-six women were randomly assigned to the combination arm and 65 to fulvestrant alone.[30]

Median PFS was 10.3 months on the combination arm and 5.1 months on the fulvestrant-alone arm (HR, 0.61; 95% CI, 0.40−0.92; P = .02).[30][Level of evidence B1]

PrE0102 (NCT01797120) was a double-blind, randomized, phase II trial comparing fulvestrant with fulvestrant plus everolimus in postmenopausal women whose disease had progressed after receiving an AI in the adjuvant or metastatic setting. Sixty-six women were randomly assigned to the combination arm and 65 to fulvestrant alone.[30]

Toxicities were similar to those in previous studies.

PrE0102 (NCT01797120) was a double-blind, randomized, phase II trial comparing fulvestrant with fulvestrant plus everolimus in postmenopausal women whose disease had progressed after receiving an AI in the adjuvant or metastatic setting. Sixty-six women were randomly assigned to the combination arm and 65 to fulvestrant alone.[30]

The was no observed difference in OS between the arms.

The single-arm SWISH trial (NCT02069093) assessed the efficacy of a dexamethasone oral solution (0.5 mg per 5 mL) in the prevention of stomatitis in women receiving exemestane plus everolimus.[31] The incidence of grade 2 or worse stomatitis was 2% in the 85 evaluable patients in this study compared with 33% in the BOLERO-2 trial.