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In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach.
In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events.
Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.
A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)
Additional Reference
1. André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904
In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach.
In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events.
Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.
A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)
Additional Reference
1. André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904
In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach.
In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events.
Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.
A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)
Additional Reference
1. André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904