Clinical Edge Journal Scan

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) treated with pertuzumab, trastuzumab, and docetaxel, rash during treatment and diarrhea after docetaxel discontinuation are predictors of survival outcomes.

Major finding: Development of rash during docetaxel administration predicted progression-free survival (PFS; adjusted hazard ratio [aHR], 0.71; P = .006) and overall survival (OS; aHR, 0.66; P = .01). Development of rash after docetaxel interruption also predicted PFS (aHR, 0.55; P = .002) and OS (aHR, 0.52; P = .018). Diarrhea was prognostic only for PFS (aHR, 0.65; P = .011) after docetaxel discontinuation.

Study details: The data come from a retrospective analysis of CLEOPATRA trial involving 777 patients with de novo or recurrent advanced HER2-positive MBC treated with docetaxel plus trastuzumab with or without pertuzumab.

Disclosures: No specific funding source was identified. Some authors reported receiving travel grants, consultation fees, and honoraria from various pharmaceutical companies.

Source: Ferreira AR et al. Eur J Cancer. 2020 Dec 31. doi: 10.1016/j.ejca.2020.11.023.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) treated with pertuzumab, trastuzumab, and docetaxel, rash during treatment and diarrhea after docetaxel discontinuation are predictors of survival outcomes.

Major finding: Development of rash during docetaxel administration predicted progression-free survival (PFS; adjusted hazard ratio [aHR], 0.71; P = .006) and overall survival (OS; aHR, 0.66; P = .01). Development of rash after docetaxel interruption also predicted PFS (aHR, 0.55; P = .002) and OS (aHR, 0.52; P = .018). Diarrhea was prognostic only for PFS (aHR, 0.65; P = .011) after docetaxel discontinuation.

Study details: The data come from a retrospective analysis of CLEOPATRA trial involving 777 patients with de novo or recurrent advanced HER2-positive MBC treated with docetaxel plus trastuzumab with or without pertuzumab.

Disclosures: No specific funding source was identified. Some authors reported receiving travel grants, consultation fees, and honoraria from various pharmaceutical companies.

Source: Ferreira AR et al. Eur J Cancer. 2020 Dec 31. doi: 10.1016/j.ejca.2020.11.023.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) treated with pertuzumab, trastuzumab, and docetaxel, rash during treatment and diarrhea after docetaxel discontinuation are predictors of survival outcomes.

Major finding: Development of rash during docetaxel administration predicted progression-free survival (PFS; adjusted hazard ratio [aHR], 0.71; P = .006) and overall survival (OS; aHR, 0.66; P = .01). Development of rash after docetaxel interruption also predicted PFS (aHR, 0.55; P = .002) and OS (aHR, 0.52; P = .018). Diarrhea was prognostic only for PFS (aHR, 0.65; P = .011) after docetaxel discontinuation.

Study details: The data come from a retrospective analysis of CLEOPATRA trial involving 777 patients with de novo or recurrent advanced HER2-positive MBC treated with docetaxel plus trastuzumab with or without pertuzumab.

Disclosures: No specific funding source was identified. Some authors reported receiving travel grants, consultation fees, and honoraria from various pharmaceutical companies.

Source: Ferreira AR et al. Eur J Cancer. 2020 Dec 31. doi: 10.1016/j.ejca.2020.11.023.

Key clinical point: Hormone therapy (HT) use and benign breast disease (BBD) history are more strongly associated with a higher risk for symptom-detected breast cancer (sym-BC), whereas alcohol intake and obesity are associated with an increased screen-detected BC (scrn-BC) risk.

Major finding: Factors more strongly associated with higher sym-BC vs. scrn-BC risk were estrogen HT use (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [CI], 1.15-1.71 vs. aHR, 0.95; 95% CI, 0.83-1.09), combined HT use (aHR, 2.07; 95% CI, 1.72-2.48 vs. aHR, 1.45; 95% CI, 1.27-1.65), and BBD history (aHR, 95% CI, 1.85; 1.64-2.08 vs. aHR, 1.43; 95% CI, 1.33-1.55). Factors more strongly associated with scrn-BC vs. sym-BC risk were alcohol intake (per drink aHR, 1.28; 95% CI, 1.18-1.39 vs. aHR, 1.07; 95% CI, 0.94-1.22) and body mass index ³30 kg/m² (aHR, 1.22; 95% CI, 1.01-1.48 vs. aHR, 0.76; 95% CI, 0.56-1.01).

Study details: The data come from an analysis of 77,206 women followed-up for a median of 14.8 years. BC was detected through screening or by symptoms in 2,711 and 1,281 women, respectively.

Disclosures: The study was supported by the American Cancer Society. The authors declared no conflicts of interest.

Source: Gaudet MM et al. Breast Cancer Res Treat. 2021 Jan 4. doi: 10.1007/s10549-020-06025-2.

Key clinical point: Hormone therapy (HT) use and benign breast disease (BBD) history are more strongly associated with a higher risk for symptom-detected breast cancer (sym-BC), whereas alcohol intake and obesity are associated with an increased screen-detected BC (scrn-BC) risk.

Major finding: Factors more strongly associated with higher sym-BC vs. scrn-BC risk were estrogen HT use (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [CI], 1.15-1.71 vs. aHR, 0.95; 95% CI, 0.83-1.09), combined HT use (aHR, 2.07; 95% CI, 1.72-2.48 vs. aHR, 1.45; 95% CI, 1.27-1.65), and BBD history (aHR, 95% CI, 1.85; 1.64-2.08 vs. aHR, 1.43; 95% CI, 1.33-1.55). Factors more strongly associated with scrn-BC vs. sym-BC risk were alcohol intake (per drink aHR, 1.28; 95% CI, 1.18-1.39 vs. aHR, 1.07; 95% CI, 0.94-1.22) and body mass index ³30 kg/m² (aHR, 1.22; 95% CI, 1.01-1.48 vs. aHR, 0.76; 95% CI, 0.56-1.01).

Study details: The data come from an analysis of 77,206 women followed-up for a median of 14.8 years. BC was detected through screening or by symptoms in 2,711 and 1,281 women, respectively.

Disclosures: The study was supported by the American Cancer Society. The authors declared no conflicts of interest.

Source: Gaudet MM et al. Breast Cancer Res Treat. 2021 Jan 4. doi: 10.1007/s10549-020-06025-2.

Key clinical point: Hormone therapy (HT) use and benign breast disease (BBD) history are more strongly associated with a higher risk for symptom-detected breast cancer (sym-BC), whereas alcohol intake and obesity are associated with an increased screen-detected BC (scrn-BC) risk.

Major finding: Factors more strongly associated with higher sym-BC vs. scrn-BC risk were estrogen HT use (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [CI], 1.15-1.71 vs. aHR, 0.95; 95% CI, 0.83-1.09), combined HT use (aHR, 2.07; 95% CI, 1.72-2.48 vs. aHR, 1.45; 95% CI, 1.27-1.65), and BBD history (aHR, 95% CI, 1.85; 1.64-2.08 vs. aHR, 1.43; 95% CI, 1.33-1.55). Factors more strongly associated with scrn-BC vs. sym-BC risk were alcohol intake (per drink aHR, 1.28; 95% CI, 1.18-1.39 vs. aHR, 1.07; 95% CI, 0.94-1.22) and body mass index ³30 kg/m² (aHR, 1.22; 95% CI, 1.01-1.48 vs. aHR, 0.76; 95% CI, 0.56-1.01).

Study details: The data come from an analysis of 77,206 women followed-up for a median of 14.8 years. BC was detected through screening or by symptoms in 2,711 and 1,281 women, respectively.

Disclosures: The study was supported by the American Cancer Society. The authors declared no conflicts of interest.

Source: Gaudet MM et al. Breast Cancer Res Treat. 2021 Jan 4. doi: 10.1007/s10549-020-06025-2.

Key clinical point: Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous (SC) injection was noninferior to intravenous (IV) dosing in patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer.

Major finding: Geometric mean ratio of cycle 7 pertuzumab serum C_trough of the SC group to the IV group was 1.22 (90% confidence interval, 1.14-1.31). Total pathologic complete response was achieved by 59.5% and 59.7% of patients in IV and SC groups, respectively. Common grade 3-4 adverse events were similar.

Study details: In the phase 3 FeDeriCa trial, patients with HER2+ early breast cancer were randomly assigned to receive either fixed-dose SC (n = 248) or IV (n = 252) pertuzumab and trastuzumab along with neoadjuvant chemotherapy.

Disclosures: This study was funded by F Hoffmann-La Roche and Genentech. The lead author AR Tan reported receving financial support from F Hoffmann-La Roche, Genentech, Pfizer, Merck, Tesaro, Novartis, Immunomedics, Celgene, and AbbVie. His coauthors also reported relationships with various pharmaceutical companies including F Hoffmann-La Roche and Genentech.

Source: Tan AR et al. Lancet Oncol. 2020 Dec 21. doi: 10.1016/S1470-2045(20)30536-2.

Key clinical point: Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous (SC) injection was noninferior to intravenous (IV) dosing in patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer.

Major finding: Geometric mean ratio of cycle 7 pertuzumab serum C_trough of the SC group to the IV group was 1.22 (90% confidence interval, 1.14-1.31). Total pathologic complete response was achieved by 59.5% and 59.7% of patients in IV and SC groups, respectively. Common grade 3-4 adverse events were similar.

Study details: In the phase 3 FeDeriCa trial, patients with HER2+ early breast cancer were randomly assigned to receive either fixed-dose SC (n = 248) or IV (n = 252) pertuzumab and trastuzumab along with neoadjuvant chemotherapy.

Disclosures: This study was funded by F Hoffmann-La Roche and Genentech. The lead author AR Tan reported receving financial support from F Hoffmann-La Roche, Genentech, Pfizer, Merck, Tesaro, Novartis, Immunomedics, Celgene, and AbbVie. His coauthors also reported relationships with various pharmaceutical companies including F Hoffmann-La Roche and Genentech.

Source: Tan AR et al. Lancet Oncol. 2020 Dec 21. doi: 10.1016/S1470-2045(20)30536-2.

Key clinical point: Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous (SC) injection was noninferior to intravenous (IV) dosing in patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer.

Major finding: Geometric mean ratio of cycle 7 pertuzumab serum C_trough of the SC group to the IV group was 1.22 (90% confidence interval, 1.14-1.31). Total pathologic complete response was achieved by 59.5% and 59.7% of patients in IV and SC groups, respectively. Common grade 3-4 adverse events were similar.

Study details: In the phase 3 FeDeriCa trial, patients with HER2+ early breast cancer were randomly assigned to receive either fixed-dose SC (n = 248) or IV (n = 252) pertuzumab and trastuzumab along with neoadjuvant chemotherapy.

Disclosures: This study was funded by F Hoffmann-La Roche and Genentech. The lead author AR Tan reported receving financial support from F Hoffmann-La Roche, Genentech, Pfizer, Merck, Tesaro, Novartis, Immunomedics, Celgene, and AbbVie. His coauthors also reported relationships with various pharmaceutical companies including F Hoffmann-La Roche and Genentech.

Source: Tan AR et al. Lancet Oncol. 2020 Dec 21. doi: 10.1016/S1470-2045(20)30536-2.

Key clinical point: In patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (ER⁺/HER2⁻ BC), adjuvant S-1 plus standard endocrine therapy (ET) significantly reduced invasive disease-free survival (IDFS) events compared with ET alone.

Major finding: IDFS events were observed in 16% vs. 11% of patients in ET-only vs. ET+S-1 groups (hazard ratio [HR], 0.63; P = .0003), respectively. The estimated 5-year IDFS was 87% in the ET+S-1 group vs. 82% in the ET-only group. However, adverse events were higher in patients receiving ET+S-1 therapy (99%) vs. ET alone (79%) but were majorly manageable.

 Study details: Phase 3 trial included 1,930 women with ER⁺/HER⁻ BC with intermediate to high risk for recurrence who were randomly allocated to receive either ET alone (n=973) or ET+S-1 (n=957) for a median follow-up of 52.2 months.

Disclosures: This study was sponsored by the Public Health Research Foundation, Japan, and funded by Taiho Pharmaceuticals. Masakazu Toi and other study authors reported funding and ties with various pharmaceutical companies including Taiho during and outside the conduct of the study.

Source: Toi M et al. Lancet Oncol. 2021 Jan 1. doi: 10.1016/S1470-2045(20)30534-9.

Key clinical point: In patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (ER⁺/HER2⁻ BC), adjuvant S-1 plus standard endocrine therapy (ET) significantly reduced invasive disease-free survival (IDFS) events compared with ET alone.

Major finding: IDFS events were observed in 16% vs. 11% of patients in ET-only vs. ET+S-1 groups (hazard ratio [HR], 0.63; P = .0003), respectively. The estimated 5-year IDFS was 87% in the ET+S-1 group vs. 82% in the ET-only group. However, adverse events were higher in patients receiving ET+S-1 therapy (99%) vs. ET alone (79%) but were majorly manageable.

 Study details: Phase 3 trial included 1,930 women with ER⁺/HER⁻ BC with intermediate to high risk for recurrence who were randomly allocated to receive either ET alone (n=973) or ET+S-1 (n=957) for a median follow-up of 52.2 months.

Disclosures: This study was sponsored by the Public Health Research Foundation, Japan, and funded by Taiho Pharmaceuticals. Masakazu Toi and other study authors reported funding and ties with various pharmaceutical companies including Taiho during and outside the conduct of the study.

Source: Toi M et al. Lancet Oncol. 2021 Jan 1. doi: 10.1016/S1470-2045(20)30534-9.

Key clinical point: In patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (ER⁺/HER2⁻ BC), adjuvant S-1 plus standard endocrine therapy (ET) significantly reduced invasive disease-free survival (IDFS) events compared with ET alone.

Major finding: IDFS events were observed in 16% vs. 11% of patients in ET-only vs. ET+S-1 groups (hazard ratio [HR], 0.63; P = .0003), respectively. The estimated 5-year IDFS was 87% in the ET+S-1 group vs. 82% in the ET-only group. However, adverse events were higher in patients receiving ET+S-1 therapy (99%) vs. ET alone (79%) but were majorly manageable.

 Study details: Phase 3 trial included 1,930 women with ER⁺/HER⁻ BC with intermediate to high risk for recurrence who were randomly allocated to receive either ET alone (n=973) or ET+S-1 (n=957) for a median follow-up of 52.2 months.

Disclosures: This study was sponsored by the Public Health Research Foundation, Japan, and funded by Taiho Pharmaceuticals. Masakazu Toi and other study authors reported funding and ties with various pharmaceutical companies including Taiho during and outside the conduct of the study.

Source: Toi M et al. Lancet Oncol. 2021 Jan 1. doi: 10.1016/S1470-2045(20)30534-9.

Key clinical point: Metabolic syndrome (MS) is associated with poorer disease-free survival (DFS), but not with overall survival (OS) in patients with triple-negative breast cancer (TNBC). Hypertension was the only MS component associated with poor DFS and OS.

Major finding: MS was significantly associated with poor DFS (adjusted HR [aHR], 2.24; P = .030), but not OS (aHR, 1.92; P = .103). Hypertension was significantly associated with worse DFS (aHR, 3.63; P = .006) and OS (aHR, 3.45; P = .035).

Study details: Retrospective study of 177 patients with TNBC with (n=48) or without (n=129) MS who were followed-up for at least 5 years.

Disclosures: The study was supported by the Sharpe Strumia Foundation. The authors declared no conflicts of interest.

Source: Kennard K et al. Breast Cancer Res Treat. 2021 Jan 3. doi: 10.1007/s10549-020-06034-1.

Key clinical point: Metabolic syndrome (MS) is associated with poorer disease-free survival (DFS), but not with overall survival (OS) in patients with triple-negative breast cancer (TNBC). Hypertension was the only MS component associated with poor DFS and OS.

Major finding: MS was significantly associated with poor DFS (adjusted HR [aHR], 2.24; P = .030), but not OS (aHR, 1.92; P = .103). Hypertension was significantly associated with worse DFS (aHR, 3.63; P = .006) and OS (aHR, 3.45; P = .035).

Study details: Retrospective study of 177 patients with TNBC with (n=48) or without (n=129) MS who were followed-up for at least 5 years.

Disclosures: The study was supported by the Sharpe Strumia Foundation. The authors declared no conflicts of interest.

Source: Kennard K et al. Breast Cancer Res Treat. 2021 Jan 3. doi: 10.1007/s10549-020-06034-1.

Key clinical point: Metabolic syndrome (MS) is associated with poorer disease-free survival (DFS), but not with overall survival (OS) in patients with triple-negative breast cancer (TNBC). Hypertension was the only MS component associated with poor DFS and OS.

Major finding: MS was significantly associated with poor DFS (adjusted HR [aHR], 2.24; P = .030), but not OS (aHR, 1.92; P = .103). Hypertension was significantly associated with worse DFS (aHR, 3.63; P = .006) and OS (aHR, 3.45; P = .035).

Study details: Retrospective study of 177 patients with TNBC with (n=48) or without (n=129) MS who were followed-up for at least 5 years.

Disclosures: The study was supported by the Sharpe Strumia Foundation. The authors declared no conflicts of interest.

Source: Kennard K et al. Breast Cancer Res Treat. 2021 Jan 3. doi: 10.1007/s10549-020-06034-1.

Key clinical point: Palbociclib+endocrine therapy (ET) did not yield superior progression-free survival (PFS) vs. capecitabine in patients with aromatase inhibitor-resistant metastatic breast cancer (AIR-MBC) but was well tolerated and improved quality of life (QoL).

Major finding: Median PFS with palbociclib+fulvestrant vs. capecitabine was 7.5 vs. 10.0 months (adjusted hazard ratio [aHR], 1.13; P = .398). Palbociclib+ET did not show PFS superiority vs. capecitabine in patients with wild-type estrogen receptor-1 AIR-MBC (8.0 vs. 10.6 months; aHR, 1.11; P = .404). Palbociclib+ET was better tolerated and improved QoL (aHR, 0.67; P = .001).

Study details: Phase 3 PEARL trial randomly allocated postmenopausal women with AIR-MBC to receive either palbociclib+exemestane or capecitabine (n=296) or palbociclib+fulvestrant or capecitabine (n=305).

Disclosures: This study was supported by Pfizer and AstraZeneca and sponsored by GEICAM Spanish Breast Cancer Group. The lead author reported ties with AstraZeneca, Pfizer, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, and Daiichi-Sankyo. Other investigators reported owning stocks, being an employee, receiving support, and/or consulting for various pharmaceutical companies including Pfizer and AstraZeneca.

Source: Martin M et al. Ann Oncol. 2020 Dec 29. doi: 10.1016/j.annonc.2020.12.013.

Key clinical point: Palbociclib+endocrine therapy (ET) did not yield superior progression-free survival (PFS) vs. capecitabine in patients with aromatase inhibitor-resistant metastatic breast cancer (AIR-MBC) but was well tolerated and improved quality of life (QoL).

Major finding: Median PFS with palbociclib+fulvestrant vs. capecitabine was 7.5 vs. 10.0 months (adjusted hazard ratio [aHR], 1.13; P = .398). Palbociclib+ET did not show PFS superiority vs. capecitabine in patients with wild-type estrogen receptor-1 AIR-MBC (8.0 vs. 10.6 months; aHR, 1.11; P = .404). Palbociclib+ET was better tolerated and improved QoL (aHR, 0.67; P = .001).

Study details: Phase 3 PEARL trial randomly allocated postmenopausal women with AIR-MBC to receive either palbociclib+exemestane or capecitabine (n=296) or palbociclib+fulvestrant or capecitabine (n=305).

Disclosures: This study was supported by Pfizer and AstraZeneca and sponsored by GEICAM Spanish Breast Cancer Group. The lead author reported ties with AstraZeneca, Pfizer, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, and Daiichi-Sankyo. Other investigators reported owning stocks, being an employee, receiving support, and/or consulting for various pharmaceutical companies including Pfizer and AstraZeneca.

Source: Martin M et al. Ann Oncol. 2020 Dec 29. doi: 10.1016/j.annonc.2020.12.013.

Key clinical point: Palbociclib+endocrine therapy (ET) did not yield superior progression-free survival (PFS) vs. capecitabine in patients with aromatase inhibitor-resistant metastatic breast cancer (AIR-MBC) but was well tolerated and improved quality of life (QoL).

Major finding: Median PFS with palbociclib+fulvestrant vs. capecitabine was 7.5 vs. 10.0 months (adjusted hazard ratio [aHR], 1.13; P = .398). Palbociclib+ET did not show PFS superiority vs. capecitabine in patients with wild-type estrogen receptor-1 AIR-MBC (8.0 vs. 10.6 months; aHR, 1.11; P = .404). Palbociclib+ET was better tolerated and improved QoL (aHR, 0.67; P = .001).

Study details: Phase 3 PEARL trial randomly allocated postmenopausal women with AIR-MBC to receive either palbociclib+exemestane or capecitabine (n=296) or palbociclib+fulvestrant or capecitabine (n=305).

Disclosures: This study was supported by Pfizer and AstraZeneca and sponsored by GEICAM Spanish Breast Cancer Group. The lead author reported ties with AstraZeneca, Pfizer, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, and Daiichi-Sankyo. Other investigators reported owning stocks, being an employee, receiving support, and/or consulting for various pharmaceutical companies including Pfizer and AstraZeneca.

Source: Martin M et al. Ann Oncol. 2020 Dec 29. doi: 10.1016/j.annonc.2020.12.013.

Key clinical point: Incidence of brain metastases is high in patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative metastatic breast cancer (MBC), highlighting the need for relevant screening in these high-risk populations.

Major finding: The pooled cumulative incidence of brain metastases in patients with HER2+ and triple-negative MBC was 31% (interquartile range [IQR], 24.0-34.0) and 32% (IQR,18.5-40.6) during a median follow-up of 30.7 and 32.8 months, respectively. The incidence of brain metastases per patient-year was 13% for HER2+ and triple negative MBC.

Study details: Meta-analysis of 25 studies including patients with HER2+ MBC (n=5,971), triple-negative (n=4,102), and hormone receptor+/HER2− MBC (n=14,656).

Disclosures: This study did not receive any funding. The lead author reported no disclosures. Some of his coinvestigators reported ties with various pharmaceutical companies.

Source: Kuksis M et al. Neuro Oncol. 2020 Dec 23. doi: 10.1093/neuonc/noaa285.

Key clinical point: Incidence of brain metastases is high in patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative metastatic breast cancer (MBC), highlighting the need for relevant screening in these high-risk populations.

Major finding: The pooled cumulative incidence of brain metastases in patients with HER2+ and triple-negative MBC was 31% (interquartile range [IQR], 24.0-34.0) and 32% (IQR,18.5-40.6) during a median follow-up of 30.7 and 32.8 months, respectively. The incidence of brain metastases per patient-year was 13% for HER2+ and triple negative MBC.

Study details: Meta-analysis of 25 studies including patients with HER2+ MBC (n=5,971), triple-negative (n=4,102), and hormone receptor+/HER2− MBC (n=14,656).

Disclosures: This study did not receive any funding. The lead author reported no disclosures. Some of his coinvestigators reported ties with various pharmaceutical companies.

Source: Kuksis M et al. Neuro Oncol. 2020 Dec 23. doi: 10.1093/neuonc/noaa285.

Key clinical point: Incidence of brain metastases is high in patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative metastatic breast cancer (MBC), highlighting the need for relevant screening in these high-risk populations.

Major finding: The pooled cumulative incidence of brain metastases in patients with HER2+ and triple-negative MBC was 31% (interquartile range [IQR], 24.0-34.0) and 32% (IQR,18.5-40.6) during a median follow-up of 30.7 and 32.8 months, respectively. The incidence of brain metastases per patient-year was 13% for HER2+ and triple negative MBC.

Study details: Meta-analysis of 25 studies including patients with HER2+ MBC (n=5,971), triple-negative (n=4,102), and hormone receptor+/HER2− MBC (n=14,656).

Disclosures: This study did not receive any funding. The lead author reported no disclosures. Some of his coinvestigators reported ties with various pharmaceutical companies.

Source: Kuksis M et al. Neuro Oncol. 2020 Dec 23. doi: 10.1093/neuonc/noaa285.

Key clinical point: Rates of ipsilateral breast tumor recurrence (IBTR) were similar between partial breast irradiation (PBI) and whole breast irradiation (WBI). Acute skin toxicities were lower with PBI.

Major finding: The rate of IBTR at 5 years was not different between PBI (1.8%; 95% highest posterior density [HPD], 0.68%-3.2%) and WBI (1.7%; 95% HPD, 0.92%-2.4%). Rates of grade 2 or greater acute skin toxicity were lower with PBI (7.1%; 95% HPD, 0%-63.4%) vs. WBI (47.5%; 95% HPD, 0%-93.4%).

Study details: Meta-analysis of 7 randomized trials including 9,758 patients receiving either WBI (n=4,840) or PBI (n=4,918).

Disclosures: No funding source was identified. The lead author reported ties with Impedimed, PreludeDX, Varian Medical Systems, and Vision RT. Some other coinvestigators reported receiving grants or consultation fees from various pharmaceutical companies.

Source: Shah C et al. Ann Surg Oncol. 2021 Jan 3. doi: 10.1245/s10434-020-09447-w.

Key clinical point: Rates of ipsilateral breast tumor recurrence (IBTR) were similar between partial breast irradiation (PBI) and whole breast irradiation (WBI). Acute skin toxicities were lower with PBI.

Major finding: The rate of IBTR at 5 years was not different between PBI (1.8%; 95% highest posterior density [HPD], 0.68%-3.2%) and WBI (1.7%; 95% HPD, 0.92%-2.4%). Rates of grade 2 or greater acute skin toxicity were lower with PBI (7.1%; 95% HPD, 0%-63.4%) vs. WBI (47.5%; 95% HPD, 0%-93.4%).

Study details: Meta-analysis of 7 randomized trials including 9,758 patients receiving either WBI (n=4,840) or PBI (n=4,918).

Disclosures: No funding source was identified. The lead author reported ties with Impedimed, PreludeDX, Varian Medical Systems, and Vision RT. Some other coinvestigators reported receiving grants or consultation fees from various pharmaceutical companies.

Source: Shah C et al. Ann Surg Oncol. 2021 Jan 3. doi: 10.1245/s10434-020-09447-w.

Key clinical point: Rates of ipsilateral breast tumor recurrence (IBTR) were similar between partial breast irradiation (PBI) and whole breast irradiation (WBI). Acute skin toxicities were lower with PBI.

Major finding: The rate of IBTR at 5 years was not different between PBI (1.8%; 95% highest posterior density [HPD], 0.68%-3.2%) and WBI (1.7%; 95% HPD, 0.92%-2.4%). Rates of grade 2 or greater acute skin toxicity were lower with PBI (7.1%; 95% HPD, 0%-63.4%) vs. WBI (47.5%; 95% HPD, 0%-93.4%).

Study details: Meta-analysis of 7 randomized trials including 9,758 patients receiving either WBI (n=4,840) or PBI (n=4,918).

Disclosures: No funding source was identified. The lead author reported ties with Impedimed, PreludeDX, Varian Medical Systems, and Vision RT. Some other coinvestigators reported receiving grants or consultation fees from various pharmaceutical companies.

Source: Shah C et al. Ann Surg Oncol. 2021 Jan 3. doi: 10.1245/s10434-020-09447-w.

Systemic therapy advances for metastatic breast cancer (MBC) have led to improved overall survival; however, the CNS sanctuary site can be challenging to treat and cause significant neurologic symptoms. Kuksis and colleagues reported that HER2-positive and triple-negative breast MBC subtypes have high incidence of brain metastases, with pooled cumulative incidences of 31% and 32%, respectively. The incidence per patient-year was 13% for both subtypes. The treatment landscape for HER2-positive MBC is rapidly evolving. The combination of tucatinib/capecitabine/trastuzumab demonstrated reduced risk of intracranial progression or death (HR 0.32), improvement in intracranial objective response rate (47.3% versus 20.0%) and reduced risk of death (0.58) in the HER2CLIMB study. An MRI screening program may enhance early detection and study prevention of brain metastases.

Trastuzumab and pertuzumab have significantly improved outcomes in early-stage and advanced HER2-positive breast cancer. These monoclonal antibodies are given with chemotherapy initially, followed by dual antibody therapy to complete one year for curative treatment and until disease progression in the metastatic setting. The FeDeriCa randomized phase 3 study demonstrated that fixed-dose subcutaneous combination of pertuzumab and trastuzumab was non-inferior to intravenous formulations with a geometric mean ratio of cycle 7 pertuzumab serum trough concentration of 1.22 (90% CI 1.14-1.31). Furthermore, efficacy appeared similar with pathologic complete response rates of 60% for both groups. Trastuzumab and pertuzumab administration in an infusion center requires hospital resources, cost, and patient’s time. The MetasphHER study showed that patients preferred subcutaneous trastuzumab compared to IV, and further investigation into long-term outcomes and impact on quality of life and resource allocation is desired.

The phase 3 CLEOPATRA study demonstrated improvement in overall survival with the addition of pertuzumab to docetaxel and trastuzumab in patients with HER2-positive MBC. Rash and diarrhea are well-recognized potential side effects related to pertuzumab. Ferreira et al demonstrated that rash was prognostic for PFS and OS both during and after docetaxel discontinuation, while diarrhea was only prognostic after docetaxel. Neither rash nor diarrhea were predictive of pertuzumab benefit. Studies have shown that patients who developed immune-related adverse events during anti-PD-1 treatment had PFS and OS benefit compared to those who did not. These results may help inform and encourage patients and providers regarding benefit of various treatments in the setting of toxicities. Future research exploring biomarker prognostic and predictive capability is certainly warranted. 

Endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for hormone receptor-positive MBC. Progression that occurs rapidly or through multiple lines of endocrine therapy combinations, may indicate endocrine resistance. The phase 3 PEARL trial did not demonstrate superior PFS among patients with wild type ESR1 AI-resistant MBC with palbociclib/endocrine therapy compared to capecitabine (mPFS 8.0 vs 10.6 months, adjusted HR 1.11; p=0.404); similar PFS and aHR were seen in palbociclib/fulvestrant versus capecitabine cohort. Therapy sequencing in HR+/HER2-negative MBC is indeed relevant, and a previous meta-analysis demonstrated chemotherapy was not better than endocrine therapy plus CDK 4/6 inhibitor in first- or second-line setting. Importantly, palbociclib plus endocrine therapy was associated with better tolerability and quality of life, which should be considered when selecting treatment with similar PFS outcomes.

References:

Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38:2610-2619.

Pivot X, Spano JP, Espie M, Cottu P, Jouannaud C, Pottier V, Moreau L, Extra JM, Lortholary A, Rivera P, Spaeth D, Attar-Rabia H, Benkanoun C, Dima-Martinez L, Esposito N, Gligorov J. Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study. Eur J Cancer. 2017;82:230-236.

Das S, Ciombor KK, Haraldsdottir S, Pumpalova Y, Sahin IH, Pineda G, Shyr Y, Lin EP, Hsu CY, Chu SK, Goff LW, Cardin DB, Bilen MA, Fisher GA, Wu C, Berlin J. Immune-related adverse events and immune checkpoint inhibitor efficacy in patients with gastrointestinal cancer with Food and Drug Administration-approved indications for immunotherapy. Oncologist. 2020;25:669-679.

Giuliano M, Schettini F, Rognoni C, Milani M, Jerusalem G, Bachelot T, De Laurentiis M, Thomas G, De Placido P, Arpino G, De Placido S, Cristofanilli M, Giordano A, Puglisi F, Pistilli B, Prat A, Del Mastro L, Venturini S, Generali D. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. Lancet Oncol. 2019;20:1360-1369.

Systemic therapy advances for metastatic breast cancer (MBC) have led to improved overall survival; however, the CNS sanctuary site can be challenging to treat and cause significant neurologic symptoms. Kuksis and colleagues reported that HER2-positive and triple-negative breast MBC subtypes have high incidence of brain metastases, with pooled cumulative incidences of 31% and 32%, respectively. The incidence per patient-year was 13% for both subtypes. The treatment landscape for HER2-positive MBC is rapidly evolving. The combination of tucatinib/capecitabine/trastuzumab demonstrated reduced risk of intracranial progression or death (HR 0.32), improvement in intracranial objective response rate (47.3% versus 20.0%) and reduced risk of death (0.58) in the HER2CLIMB study. An MRI screening program may enhance early detection and study prevention of brain metastases.

Trastuzumab and pertuzumab have significantly improved outcomes in early-stage and advanced HER2-positive breast cancer. These monoclonal antibodies are given with chemotherapy initially, followed by dual antibody therapy to complete one year for curative treatment and until disease progression in the metastatic setting. The FeDeriCa randomized phase 3 study demonstrated that fixed-dose subcutaneous combination of pertuzumab and trastuzumab was non-inferior to intravenous formulations with a geometric mean ratio of cycle 7 pertuzumab serum trough concentration of 1.22 (90% CI 1.14-1.31). Furthermore, efficacy appeared similar with pathologic complete response rates of 60% for both groups. Trastuzumab and pertuzumab administration in an infusion center requires hospital resources, cost, and patient’s time. The MetasphHER study showed that patients preferred subcutaneous trastuzumab compared to IV, and further investigation into long-term outcomes and impact on quality of life and resource allocation is desired.

The phase 3 CLEOPATRA study demonstrated improvement in overall survival with the addition of pertuzumab to docetaxel and trastuzumab in patients with HER2-positive MBC. Rash and diarrhea are well-recognized potential side effects related to pertuzumab. Ferreira et al demonstrated that rash was prognostic for PFS and OS both during and after docetaxel discontinuation, while diarrhea was only prognostic after docetaxel. Neither rash nor diarrhea were predictive of pertuzumab benefit. Studies have shown that patients who developed immune-related adverse events during anti-PD-1 treatment had PFS and OS benefit compared to those who did not. These results may help inform and encourage patients and providers regarding benefit of various treatments in the setting of toxicities. Future research exploring biomarker prognostic and predictive capability is certainly warranted. 

Endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for hormone receptor-positive MBC. Progression that occurs rapidly or through multiple lines of endocrine therapy combinations, may indicate endocrine resistance. The phase 3 PEARL trial did not demonstrate superior PFS among patients with wild type ESR1 AI-resistant MBC with palbociclib/endocrine therapy compared to capecitabine (mPFS 8.0 vs 10.6 months, adjusted HR 1.11; p=0.404); similar PFS and aHR were seen in palbociclib/fulvestrant versus capecitabine cohort. Therapy sequencing in HR+/HER2-negative MBC is indeed relevant, and a previous meta-analysis demonstrated chemotherapy was not better than endocrine therapy plus CDK 4/6 inhibitor in first- or second-line setting. Importantly, palbociclib plus endocrine therapy was associated with better tolerability and quality of life, which should be considered when selecting treatment with similar PFS outcomes.

References:

Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38:2610-2619.

Pivot X, Spano JP, Espie M, Cottu P, Jouannaud C, Pottier V, Moreau L, Extra JM, Lortholary A, Rivera P, Spaeth D, Attar-Rabia H, Benkanoun C, Dima-Martinez L, Esposito N, Gligorov J. Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study. Eur J Cancer. 2017;82:230-236.

Das S, Ciombor KK, Haraldsdottir S, Pumpalova Y, Sahin IH, Pineda G, Shyr Y, Lin EP, Hsu CY, Chu SK, Goff LW, Cardin DB, Bilen MA, Fisher GA, Wu C, Berlin J. Immune-related adverse events and immune checkpoint inhibitor efficacy in patients with gastrointestinal cancer with Food and Drug Administration-approved indications for immunotherapy. Oncologist. 2020;25:669-679.

Giuliano M, Schettini F, Rognoni C, Milani M, Jerusalem G, Bachelot T, De Laurentiis M, Thomas G, De Placido P, Arpino G, De Placido S, Cristofanilli M, Giordano A, Puglisi F, Pistilli B, Prat A, Del Mastro L, Venturini S, Generali D. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. Lancet Oncol. 2019;20:1360-1369.

Systemic therapy advances for metastatic breast cancer (MBC) have led to improved overall survival; however, the CNS sanctuary site can be challenging to treat and cause significant neurologic symptoms. Kuksis and colleagues reported that HER2-positive and triple-negative breast MBC subtypes have high incidence of brain metastases, with pooled cumulative incidences of 31% and 32%, respectively. The incidence per patient-year was 13% for both subtypes. The treatment landscape for HER2-positive MBC is rapidly evolving. The combination of tucatinib/capecitabine/trastuzumab demonstrated reduced risk of intracranial progression or death (HR 0.32), improvement in intracranial objective response rate (47.3% versus 20.0%) and reduced risk of death (0.58) in the HER2CLIMB study. An MRI screening program may enhance early detection and study prevention of brain metastases.

Trastuzumab and pertuzumab have significantly improved outcomes in early-stage and advanced HER2-positive breast cancer. These monoclonal antibodies are given with chemotherapy initially, followed by dual antibody therapy to complete one year for curative treatment and until disease progression in the metastatic setting. The FeDeriCa randomized phase 3 study demonstrated that fixed-dose subcutaneous combination of pertuzumab and trastuzumab was non-inferior to intravenous formulations with a geometric mean ratio of cycle 7 pertuzumab serum trough concentration of 1.22 (90% CI 1.14-1.31). Furthermore, efficacy appeared similar with pathologic complete response rates of 60% for both groups. Trastuzumab and pertuzumab administration in an infusion center requires hospital resources, cost, and patient’s time. The MetasphHER study showed that patients preferred subcutaneous trastuzumab compared to IV, and further investigation into long-term outcomes and impact on quality of life and resource allocation is desired.

The phase 3 CLEOPATRA study demonstrated improvement in overall survival with the addition of pertuzumab to docetaxel and trastuzumab in patients with HER2-positive MBC. Rash and diarrhea are well-recognized potential side effects related to pertuzumab. Ferreira et al demonstrated that rash was prognostic for PFS and OS both during and after docetaxel discontinuation, while diarrhea was only prognostic after docetaxel. Neither rash nor diarrhea were predictive of pertuzumab benefit. Studies have shown that patients who developed immune-related adverse events during anti-PD-1 treatment had PFS and OS benefit compared to those who did not. These results may help inform and encourage patients and providers regarding benefit of various treatments in the setting of toxicities. Future research exploring biomarker prognostic and predictive capability is certainly warranted. 

Endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for hormone receptor-positive MBC. Progression that occurs rapidly or through multiple lines of endocrine therapy combinations, may indicate endocrine resistance. The phase 3 PEARL trial did not demonstrate superior PFS among patients with wild type ESR1 AI-resistant MBC with palbociclib/endocrine therapy compared to capecitabine (mPFS 8.0 vs 10.6 months, adjusted HR 1.11; p=0.404); similar PFS and aHR were seen in palbociclib/fulvestrant versus capecitabine cohort. Therapy sequencing in HR+/HER2-negative MBC is indeed relevant, and a previous meta-analysis demonstrated chemotherapy was not better than endocrine therapy plus CDK 4/6 inhibitor in first- or second-line setting. Importantly, palbociclib plus endocrine therapy was associated with better tolerability and quality of life, which should be considered when selecting treatment with similar PFS outcomes.

References:

Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38:2610-2619.

Pivot X, Spano JP, Espie M, Cottu P, Jouannaud C, Pottier V, Moreau L, Extra JM, Lortholary A, Rivera P, Spaeth D, Attar-Rabia H, Benkanoun C, Dima-Martinez L, Esposito N, Gligorov J. Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study. Eur J Cancer. 2017;82:230-236.

Das S, Ciombor KK, Haraldsdottir S, Pumpalova Y, Sahin IH, Pineda G, Shyr Y, Lin EP, Hsu CY, Chu SK, Goff LW, Cardin DB, Bilen MA, Fisher GA, Wu C, Berlin J. Immune-related adverse events and immune checkpoint inhibitor efficacy in patients with gastrointestinal cancer with Food and Drug Administration-approved indications for immunotherapy. Oncologist. 2020;25:669-679.

Giuliano M, Schettini F, Rognoni C, Milani M, Jerusalem G, Bachelot T, De Laurentiis M, Thomas G, De Placido P, Arpino G, De Placido S, Cristofanilli M, Giordano A, Puglisi F, Pistilli B, Prat A, Del Mastro L, Venturini S, Generali D. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. Lancet Oncol. 2019;20:1360-1369.

Key clinical point: Information of the flow cytometry immunophenotyping (FCI) data during therapy combined with the hematological response can help physicians identify patients with myelodysplastic syndrome (MDS) with a higher probability of maintaining a good quality of response to 5-azacitidine (AZA) therapy for a longer period of time.

Major finding: After a median of 6 cycles of AZA, an FCI improvement was found in 41% of patients, and this finding correlated with a better clinical response (P less than .001). FCI improvement correlated with hematological improvement (HI), and the probability of maintaining a clinical response at 12 cycles of AZA was twice as large (67%) for those who achieved an HI and an FCI improvement after 6 cycles of AZA compared with patients who only achieved an HI (33%).

Study details: The data come from a study of 81 patients diagnosed with MDS in 5 European centers.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Subirá D et al. Ann Hematol. 2021 Jan 9. doi: 10.1007/s00277-021-04411-4.

Key clinical point: Information of the flow cytometry immunophenotyping (FCI) data during therapy combined with the hematological response can help physicians identify patients with myelodysplastic syndrome (MDS) with a higher probability of maintaining a good quality of response to 5-azacitidine (AZA) therapy for a longer period of time.

Major finding: After a median of 6 cycles of AZA, an FCI improvement was found in 41% of patients, and this finding correlated with a better clinical response (P less than .001). FCI improvement correlated with hematological improvement (HI), and the probability of maintaining a clinical response at 12 cycles of AZA was twice as large (67%) for those who achieved an HI and an FCI improvement after 6 cycles of AZA compared with patients who only achieved an HI (33%).

Study details: The data come from a study of 81 patients diagnosed with MDS in 5 European centers.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Subirá D et al. Ann Hematol. 2021 Jan 9. doi: 10.1007/s00277-021-04411-4.

Key clinical point: Information of the flow cytometry immunophenotyping (FCI) data during therapy combined with the hematological response can help physicians identify patients with myelodysplastic syndrome (MDS) with a higher probability of maintaining a good quality of response to 5-azacitidine (AZA) therapy for a longer period of time.

Major finding: After a median of 6 cycles of AZA, an FCI improvement was found in 41% of patients, and this finding correlated with a better clinical response (P less than .001). FCI improvement correlated with hematological improvement (HI), and the probability of maintaining a clinical response at 12 cycles of AZA was twice as large (67%) for those who achieved an HI and an FCI improvement after 6 cycles of AZA compared with patients who only achieved an HI (33%).

Study details: The data come from a study of 81 patients diagnosed with MDS in 5 European centers.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Subirá D et al. Ann Hematol. 2021 Jan 9. doi: 10.1007/s00277-021-04411-4.