Breast Cancer

Program death-ligand 1 (PD-L1) inhibition suppresses tumor activity via modulation of immune and tumor cell interaction. TNBC is characterized by higher PD-L1 expression and increased immune infiltration, compared to other subtypes. In the randomized, phase 3 IMpassion130 trial, among 902 patients who were treatment naïve in the metastatic TNBC setting, an exploratory analysis in the PD-L1-positive population demonstrated a clinically meaningful OS benefit with atezolizumab + nab-paclitaxel compared to placebo + nab-paclitaxel (25.4 vs 17.9 months; HR 0.67) (Emens et al). Additionally, the phase 3 KEYNOTE-355 trial demonstrated PFS benefit among patients with mTNBC with combined positive score (CPS) ≥10 with pembrolizumab + chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) versus placebo + chemotherapy (mPFS 9.7 vs 5.6 months; HR 0.65, 95% CI 0.49-0.86). These results are in contrast to the phase 3 IMpassion131 trial which found no statistically significant difference in PFS or OS among 651 patients with mTNBC randomized to atezolizumab + paclitaxel vs placebo + paclitaxel (PD-L1-positive population: PFS 6.0 vs 5.7 months, HR 0.82, 95% CI 0.60-1.12; OS 22.1 vs 28.3 months, HR 1.11, 95% CI 0.76-1.62) (Miles et al). The reasons underlying these differences remain unclear and warrant further investigation. Some thoughts raised include lack of information on BRCA status (which may serve as prognostic factor) in IMpassion131, concomitant use of steroids with paclitaxel, and allowance of sufficient long-term follow-up for generation of events. Regardless, these studies suggest chemotherapy backbone is relevant and the regimens utilized in IMpassion130 and KEYNOTE-355 have gained FDA approval in the first-line mTNBC setting.

The phase 3 CLEOPATRA trial has established the regimen of docetaxel + trastuzumab + pertuzumab as standard of care in the first-line setting for metastatic HER2-positive breast cancer with an OS benefit of 16 months compared to docetaxel + trastuzumab + placebo (57.1 vs 40.8 months; HR 0.69, 95% CI 0.58-0.82) with over 8 years of follow-up. PERUSE was a single-arm phase 3b study that investigated the safety and efficacy of trastuzumab + pertuzumab combined with various taxanes (docetaxel, paclitaxel or nab-paclitaxel) among 1426 patients with HER2+ mBC (Miles et al). In the overall population at follow-up of 5.7 years, median PFS and OS were 20.7 and 65.3 months, respectively, and were similar regardless of taxane backbone. Docetaxel was associated with higher incidences of neutropenia and febrile neutropenia. These results support consideration of an alternative taxane combined with trastuzumab + pertuzumab in this setting (for example paclitaxel) in patients who may not be ideal candidates for docetaxel.

In the second-line treatment setting for HER2+ mBC with prior exposure to trastuzumab and taxane, the phase 3 EMILIA study showed improvement in OS with T-DM1 vs capecitabine + lapatinib (mOS 29.9 vs 25.9 months, HR 0.75, 95% CI 0.64-0.88). Ethier et al explored real-world application and outcomes associated with pertuzumab and T-DM1 in the first- and second-line settings respectively, in a population-based, retrospective cohort study in Ontario, Canada. In the pertuzumab cohort, median OS and time on treatment were 43 and 4 months, respectively. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively. Additionally, patients in the T-DM1 cohort who were pertuzumab-naïve appeared to do better, potentially suggesting less responsiveness to subsequent HER2-targeted treatment in the real world setting among those who received prior pertuzumab. Findings from this population study demonstrate inferior outcomes when compared to the pivotal CLEOPATRA and EMILIA trials, and highlight a gap between clinical trial and real-world observations (described by authors as efficacy-effectiveness gap). Potential etiologies for these differences include patient factors, prior therapies and delivery of care models, and convey the importance of recognizing this gap exists and optimizing any modifiable factors as trial data and novel therapies are applied to routine clinical practice.

References:

Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361-70.

Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828.

Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.

Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732-742.

Program death-ligand 1 (PD-L1) inhibition suppresses tumor activity via modulation of immune and tumor cell interaction. TNBC is characterized by higher PD-L1 expression and increased immune infiltration, compared to other subtypes. In the randomized, phase 3 IMpassion130 trial, among 902 patients who were treatment naïve in the metastatic TNBC setting, an exploratory analysis in the PD-L1-positive population demonstrated a clinically meaningful OS benefit with atezolizumab + nab-paclitaxel compared to placebo + nab-paclitaxel (25.4 vs 17.9 months; HR 0.67) (Emens et al). Additionally, the phase 3 KEYNOTE-355 trial demonstrated PFS benefit among patients with mTNBC with combined positive score (CPS) ≥10 with pembrolizumab + chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) versus placebo + chemotherapy (mPFS 9.7 vs 5.6 months; HR 0.65, 95% CI 0.49-0.86). These results are in contrast to the phase 3 IMpassion131 trial which found no statistically significant difference in PFS or OS among 651 patients with mTNBC randomized to atezolizumab + paclitaxel vs placebo + paclitaxel (PD-L1-positive population: PFS 6.0 vs 5.7 months, HR 0.82, 95% CI 0.60-1.12; OS 22.1 vs 28.3 months, HR 1.11, 95% CI 0.76-1.62) (Miles et al). The reasons underlying these differences remain unclear and warrant further investigation. Some thoughts raised include lack of information on BRCA status (which may serve as prognostic factor) in IMpassion131, concomitant use of steroids with paclitaxel, and allowance of sufficient long-term follow-up for generation of events. Regardless, these studies suggest chemotherapy backbone is relevant and the regimens utilized in IMpassion130 and KEYNOTE-355 have gained FDA approval in the first-line mTNBC setting.

The phase 3 CLEOPATRA trial has established the regimen of docetaxel + trastuzumab + pertuzumab as standard of care in the first-line setting for metastatic HER2-positive breast cancer with an OS benefit of 16 months compared to docetaxel + trastuzumab + placebo (57.1 vs 40.8 months; HR 0.69, 95% CI 0.58-0.82) with over 8 years of follow-up. PERUSE was a single-arm phase 3b study that investigated the safety and efficacy of trastuzumab + pertuzumab combined with various taxanes (docetaxel, paclitaxel or nab-paclitaxel) among 1426 patients with HER2+ mBC (Miles et al). In the overall population at follow-up of 5.7 years, median PFS and OS were 20.7 and 65.3 months, respectively, and were similar regardless of taxane backbone. Docetaxel was associated with higher incidences of neutropenia and febrile neutropenia. These results support consideration of an alternative taxane combined with trastuzumab + pertuzumab in this setting (for example paclitaxel) in patients who may not be ideal candidates for docetaxel.

In the second-line treatment setting for HER2+ mBC with prior exposure to trastuzumab and taxane, the phase 3 EMILIA study showed improvement in OS with T-DM1 vs capecitabine + lapatinib (mOS 29.9 vs 25.9 months, HR 0.75, 95% CI 0.64-0.88). Ethier et al explored real-world application and outcomes associated with pertuzumab and T-DM1 in the first- and second-line settings respectively, in a population-based, retrospective cohort study in Ontario, Canada. In the pertuzumab cohort, median OS and time on treatment were 43 and 4 months, respectively. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively. Additionally, patients in the T-DM1 cohort who were pertuzumab-naïve appeared to do better, potentially suggesting less responsiveness to subsequent HER2-targeted treatment in the real world setting among those who received prior pertuzumab. Findings from this population study demonstrate inferior outcomes when compared to the pivotal CLEOPATRA and EMILIA trials, and highlight a gap between clinical trial and real-world observations (described by authors as efficacy-effectiveness gap). Potential etiologies for these differences include patient factors, prior therapies and delivery of care models, and convey the importance of recognizing this gap exists and optimizing any modifiable factors as trial data and novel therapies are applied to routine clinical practice.

References:

Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361-70.

Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828.

Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.

Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732-742.

Program death-ligand 1 (PD-L1) inhibition suppresses tumor activity via modulation of immune and tumor cell interaction. TNBC is characterized by higher PD-L1 expression and increased immune infiltration, compared to other subtypes. In the randomized, phase 3 IMpassion130 trial, among 902 patients who were treatment naïve in the metastatic TNBC setting, an exploratory analysis in the PD-L1-positive population demonstrated a clinically meaningful OS benefit with atezolizumab + nab-paclitaxel compared to placebo + nab-paclitaxel (25.4 vs 17.9 months; HR 0.67) (Emens et al). Additionally, the phase 3 KEYNOTE-355 trial demonstrated PFS benefit among patients with mTNBC with combined positive score (CPS) ≥10 with pembrolizumab + chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) versus placebo + chemotherapy (mPFS 9.7 vs 5.6 months; HR 0.65, 95% CI 0.49-0.86). These results are in contrast to the phase 3 IMpassion131 trial which found no statistically significant difference in PFS or OS among 651 patients with mTNBC randomized to atezolizumab + paclitaxel vs placebo + paclitaxel (PD-L1-positive population: PFS 6.0 vs 5.7 months, HR 0.82, 95% CI 0.60-1.12; OS 22.1 vs 28.3 months, HR 1.11, 95% CI 0.76-1.62) (Miles et al). The reasons underlying these differences remain unclear and warrant further investigation. Some thoughts raised include lack of information on BRCA status (which may serve as prognostic factor) in IMpassion131, concomitant use of steroids with paclitaxel, and allowance of sufficient long-term follow-up for generation of events. Regardless, these studies suggest chemotherapy backbone is relevant and the regimens utilized in IMpassion130 and KEYNOTE-355 have gained FDA approval in the first-line mTNBC setting.

The phase 3 CLEOPATRA trial has established the regimen of docetaxel + trastuzumab + pertuzumab as standard of care in the first-line setting for metastatic HER2-positive breast cancer with an OS benefit of 16 months compared to docetaxel + trastuzumab + placebo (57.1 vs 40.8 months; HR 0.69, 95% CI 0.58-0.82) with over 8 years of follow-up. PERUSE was a single-arm phase 3b study that investigated the safety and efficacy of trastuzumab + pertuzumab combined with various taxanes (docetaxel, paclitaxel or nab-paclitaxel) among 1426 patients with HER2+ mBC (Miles et al). In the overall population at follow-up of 5.7 years, median PFS and OS were 20.7 and 65.3 months, respectively, and were similar regardless of taxane backbone. Docetaxel was associated with higher incidences of neutropenia and febrile neutropenia. These results support consideration of an alternative taxane combined with trastuzumab + pertuzumab in this setting (for example paclitaxel) in patients who may not be ideal candidates for docetaxel.

In the second-line treatment setting for HER2+ mBC with prior exposure to trastuzumab and taxane, the phase 3 EMILIA study showed improvement in OS with T-DM1 vs capecitabine + lapatinib (mOS 29.9 vs 25.9 months, HR 0.75, 95% CI 0.64-0.88). Ethier et al explored real-world application and outcomes associated with pertuzumab and T-DM1 in the first- and second-line settings respectively, in a population-based, retrospective cohort study in Ontario, Canada. In the pertuzumab cohort, median OS and time on treatment were 43 and 4 months, respectively. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively. Additionally, patients in the T-DM1 cohort who were pertuzumab-naïve appeared to do better, potentially suggesting less responsiveness to subsequent HER2-targeted treatment in the real world setting among those who received prior pertuzumab. Findings from this population study demonstrate inferior outcomes when compared to the pivotal CLEOPATRA and EMILIA trials, and highlight a gap between clinical trial and real-world observations (described by authors as efficacy-effectiveness gap). Potential etiologies for these differences include patient factors, prior therapies and delivery of care models, and convey the importance of recognizing this gap exists and optimizing any modifiable factors as trial data and novel therapies are applied to routine clinical practice.

References:

Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361-70.

Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828.

Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.

Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732-742.

Key clinical point: Chemotherapy is not associated with postmastectomy breast reconstruction surgical complications or with most surgery-related patient-reported outcomes.

Major finding: Compared with no chemotherapy, no difference was observed in the risk for any/major complication with either neoadjuvant (P = .68 and .46, respectively) or adjuvant (P = .15 and .053, respectively) chemotherapy in patients who received implant-based procedures. In patients who received autologous reconstruction, the risk for 2-year postoperative any/major complication was similar with neoadjuvant (P = .25 and .11, respectively) and adjuvant (P = .44 and .40, respectively) chemotherapy vs no chemotherapy. There were no differences across the chemotherapy groups for most BREAST-Q subscales.

Study details: A multicenter cohort study of 1,881 women who underwent postmastectomy breast reconstruction and were followed up for 2 years.

Disclosures: This study was supported by the National Cancer Institute. The authors did not report any conflicts of interest.

Source: Hart SE et al. JAMA Surg. 2021 Jun 23. doi: 10.1001/jamasurg.2021.2239.

Key clinical point: Chemotherapy is not associated with postmastectomy breast reconstruction surgical complications or with most surgery-related patient-reported outcomes.

Major finding: Compared with no chemotherapy, no difference was observed in the risk for any/major complication with either neoadjuvant (P = .68 and .46, respectively) or adjuvant (P = .15 and .053, respectively) chemotherapy in patients who received implant-based procedures. In patients who received autologous reconstruction, the risk for 2-year postoperative any/major complication was similar with neoadjuvant (P = .25 and .11, respectively) and adjuvant (P = .44 and .40, respectively) chemotherapy vs no chemotherapy. There were no differences across the chemotherapy groups for most BREAST-Q subscales.

Study details: A multicenter cohort study of 1,881 women who underwent postmastectomy breast reconstruction and were followed up for 2 years.

Disclosures: This study was supported by the National Cancer Institute. The authors did not report any conflicts of interest.

Source: Hart SE et al. JAMA Surg. 2021 Jun 23. doi: 10.1001/jamasurg.2021.2239.

Key clinical point: Chemotherapy is not associated with postmastectomy breast reconstruction surgical complications or with most surgery-related patient-reported outcomes.

Major finding: Compared with no chemotherapy, no difference was observed in the risk for any/major complication with either neoadjuvant (P = .68 and .46, respectively) or adjuvant (P = .15 and .053, respectively) chemotherapy in patients who received implant-based procedures. In patients who received autologous reconstruction, the risk for 2-year postoperative any/major complication was similar with neoadjuvant (P = .25 and .11, respectively) and adjuvant (P = .44 and .40, respectively) chemotherapy vs no chemotherapy. There were no differences across the chemotherapy groups for most BREAST-Q subscales.

Study details: A multicenter cohort study of 1,881 women who underwent postmastectomy breast reconstruction and were followed up for 2 years.

Disclosures: This study was supported by the National Cancer Institute. The authors did not report any conflicts of interest.

Source: Hart SE et al. JAMA Surg. 2021 Jun 23. doi: 10.1001/jamasurg.2021.2239.

Key clinical point: In the real-world setting, the overall survival (OS) with pertuzumab and trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor hormone receptor 2 (HER2)-positive metastatic breast cancer is inferior to results from pivotal clinical trials.

Major finding: The OS with pertuzumab and T-DM1 was shorter than that reported in the pivotal clinical trials. In the pertuzumab cohort, OS was 43 months and time on treatment was 14 months. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively.

Study details: A population-based retrospective cohort study of patients with ERBB2-positive metastatic breast cancer treated with first-line pertuzumab (n=795) or second-line T-DM1 (n=506).

Disclosures: This study was supported by the Canadian Institutes of Health Research. The authors received personal fees from various sources outside this work. Dr. CM Booth was supported as a Canada Research Chair in Population Cancer Care.

Source: Ethier JL et al. JAMA Oncol. 2021 Jul 8. doi: 10.1001/jamaoncol.2021.2140.

Key clinical point: In the real-world setting, the overall survival (OS) with pertuzumab and trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor hormone receptor 2 (HER2)-positive metastatic breast cancer is inferior to results from pivotal clinical trials.

Major finding: The OS with pertuzumab and T-DM1 was shorter than that reported in the pivotal clinical trials. In the pertuzumab cohort, OS was 43 months and time on treatment was 14 months. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively.

Study details: A population-based retrospective cohort study of patients with ERBB2-positive metastatic breast cancer treated with first-line pertuzumab (n=795) or second-line T-DM1 (n=506).

Disclosures: This study was supported by the Canadian Institutes of Health Research. The authors received personal fees from various sources outside this work. Dr. CM Booth was supported as a Canada Research Chair in Population Cancer Care.

Source: Ethier JL et al. JAMA Oncol. 2021 Jul 8. doi: 10.1001/jamaoncol.2021.2140.

Key clinical point: In the real-world setting, the overall survival (OS) with pertuzumab and trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor hormone receptor 2 (HER2)-positive metastatic breast cancer is inferior to results from pivotal clinical trials.

Major finding: The OS with pertuzumab and T-DM1 was shorter than that reported in the pivotal clinical trials. In the pertuzumab cohort, OS was 43 months and time on treatment was 14 months. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively.

Study details: A population-based retrospective cohort study of patients with ERBB2-positive metastatic breast cancer treated with first-line pertuzumab (n=795) or second-line T-DM1 (n=506).

Disclosures: This study was supported by the Canadian Institutes of Health Research. The authors received personal fees from various sources outside this work. Dr. CM Booth was supported as a Canada Research Chair in Population Cancer Care.

Source: Ethier JL et al. JAMA Oncol. 2021 Jul 8. doi: 10.1001/jamaoncol.2021.2140.

Key clinical point: Stereotactic ablative body radiotherapy (SABR) leads to long-term systemic disease control and survival in patients with oligometastatic breast cancer.

Major finding: The median follow-up was 50 months. Of the patients who progressed, 82% had new metastases and 18% experienced local failure. Median overall survival (OS) was 86 months, and progression-free survival (PFS) was 33 months. The receipt of SABR within 5 years of diagnosis (P = .004) and presence of triple-negative breast cancer (TNBC; P = .013) were associated with worse OS. Advanced T stage (P = .062) and TNBC (P = .013) were associated with worse PFS.

Study details: A retrospective study of patients with metastatic breast cancer who received SABR between 2008 and 2018.

Disclosures: This study was supported by the National Institutes of Health/National Cancer Institute. The authors declared no conflicts of interest.

Source: Wijetunga NA et al. Cancer Med. 2021 Jun 22. doi: 10.1002/cam4.4068.

Key clinical point: Stereotactic ablative body radiotherapy (SABR) leads to long-term systemic disease control and survival in patients with oligometastatic breast cancer.

Major finding: The median follow-up was 50 months. Of the patients who progressed, 82% had new metastases and 18% experienced local failure. Median overall survival (OS) was 86 months, and progression-free survival (PFS) was 33 months. The receipt of SABR within 5 years of diagnosis (P = .004) and presence of triple-negative breast cancer (TNBC; P = .013) were associated with worse OS. Advanced T stage (P = .062) and TNBC (P = .013) were associated with worse PFS.

Study details: A retrospective study of patients with metastatic breast cancer who received SABR between 2008 and 2018.

Disclosures: This study was supported by the National Institutes of Health/National Cancer Institute. The authors declared no conflicts of interest.

Source: Wijetunga NA et al. Cancer Med. 2021 Jun 22. doi: 10.1002/cam4.4068.

Key clinical point: Stereotactic ablative body radiotherapy (SABR) leads to long-term systemic disease control and survival in patients with oligometastatic breast cancer.

Major finding: The median follow-up was 50 months. Of the patients who progressed, 82% had new metastases and 18% experienced local failure. Median overall survival (OS) was 86 months, and progression-free survival (PFS) was 33 months. The receipt of SABR within 5 years of diagnosis (P = .004) and presence of triple-negative breast cancer (TNBC; P = .013) were associated with worse OS. Advanced T stage (P = .062) and TNBC (P = .013) were associated with worse PFS.

Study details: A retrospective study of patients with metastatic breast cancer who received SABR between 2008 and 2018.

Disclosures: This study was supported by the National Institutes of Health/National Cancer Institute. The authors declared no conflicts of interest.

Source: Wijetunga NA et al. Cancer Med. 2021 Jun 22. doi: 10.1002/cam4.4068.

Key clinical point: Denosumab improves bone-related outcomes in women with high-risk early-stage breast cancer.

Major finding: Denosumab was associated with longer time to first bone metastasis in patients younger than 50 years (hazard ratio [HR], 0.70; P = .018) and in premenopausal women (HR, 0.74; P = .038). Denosumab also delayed the risk for first fracture (HR, 0.76; P = .004) and first skeletal-related event (HR, 0.52; P = .001).

Study details: An exploratory analysis of randomized, placebo-controlled phase 3 D-CARE trial of 4,509 patients with stage II/III breast cancer randomly assigned to receive adjuvant/neoadjuvant chemotherapy with either denosumab or placebo.

Disclosures: This study was funded by Amgen Inc. Dr. R Coleman received lecture funding, steering committee fees, and travel expenses from various sources and reported stock ownership in Inbiomotion. Dr. Y. Zhou, Dr. D. Jandial, and Dr. B. Cadieux were employees of and/or shareholders in Amgen. The other authors have no competing interest.

Source: Coleman R et al. Adv Ther. 2021 Jun 29. doi: 10.1007/s12325-021-01812-9.

Key clinical point: Denosumab improves bone-related outcomes in women with high-risk early-stage breast cancer.

Major finding: Denosumab was associated with longer time to first bone metastasis in patients younger than 50 years (hazard ratio [HR], 0.70; P = .018) and in premenopausal women (HR, 0.74; P = .038). Denosumab also delayed the risk for first fracture (HR, 0.76; P = .004) and first skeletal-related event (HR, 0.52; P = .001).

Study details: An exploratory analysis of randomized, placebo-controlled phase 3 D-CARE trial of 4,509 patients with stage II/III breast cancer randomly assigned to receive adjuvant/neoadjuvant chemotherapy with either denosumab or placebo.

Disclosures: This study was funded by Amgen Inc. Dr. R Coleman received lecture funding, steering committee fees, and travel expenses from various sources and reported stock ownership in Inbiomotion. Dr. Y. Zhou, Dr. D. Jandial, and Dr. B. Cadieux were employees of and/or shareholders in Amgen. The other authors have no competing interest.

Source: Coleman R et al. Adv Ther. 2021 Jun 29. doi: 10.1007/s12325-021-01812-9.

Key clinical point: Denosumab improves bone-related outcomes in women with high-risk early-stage breast cancer.

Major finding: Denosumab was associated with longer time to first bone metastasis in patients younger than 50 years (hazard ratio [HR], 0.70; P = .018) and in premenopausal women (HR, 0.74; P = .038). Denosumab also delayed the risk for first fracture (HR, 0.76; P = .004) and first skeletal-related event (HR, 0.52; P = .001).

Study details: An exploratory analysis of randomized, placebo-controlled phase 3 D-CARE trial of 4,509 patients with stage II/III breast cancer randomly assigned to receive adjuvant/neoadjuvant chemotherapy with either denosumab or placebo.

Disclosures: This study was funded by Amgen Inc. Dr. R Coleman received lecture funding, steering committee fees, and travel expenses from various sources and reported stock ownership in Inbiomotion. Dr. Y. Zhou, Dr. D. Jandial, and Dr. B. Cadieux were employees of and/or shareholders in Amgen. The other authors have no competing interest.

Source: Coleman R et al. Adv Ther. 2021 Jun 29. doi: 10.1007/s12325-021-01812-9.

Key clinical point: The clinical benefit of ribociclib is maintained in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who required dose reduction to manage adverse events.

Major finding: Ribociclib dose reductions were reported in 45.8% of patients; most were attributed to adverse reactions. The median progression-free survival was 24.8, 24.9, and 29.6 months for patients who received 71% or less, 72%-96%, and 97%-100% ribociclib relative dose intensity, respectively. The clinical benefit ratio was 87.6%, 76.8%, and 73.6%, respectively.

Study details: A pooled analysis of MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials evaluated the safety and impact of ribociclib dose reduction in 818 patients with HR-positive, HER2-negative advanced breast cancer.

Disclosures: The study was supported by Novartis Pharmaceuticals Corporation. The authors received grants, funding, and/or consulting/advisory/personal fees from various sources. Dr. JP Zarate, Dr. A Ridolfi, and Dr. KR Lorenc were employed by and owned stocks in Novartis.

Source: Burris HA et al. Br J Cancer. 2021 Jun 22. doi: 10.1038/s41416-021-01415-9.

Key clinical point: The clinical benefit of ribociclib is maintained in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who required dose reduction to manage adverse events.

Major finding: Ribociclib dose reductions were reported in 45.8% of patients; most were attributed to adverse reactions. The median progression-free survival was 24.8, 24.9, and 29.6 months for patients who received 71% or less, 72%-96%, and 97%-100% ribociclib relative dose intensity, respectively. The clinical benefit ratio was 87.6%, 76.8%, and 73.6%, respectively.

Study details: A pooled analysis of MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials evaluated the safety and impact of ribociclib dose reduction in 818 patients with HR-positive, HER2-negative advanced breast cancer.

Disclosures: The study was supported by Novartis Pharmaceuticals Corporation. The authors received grants, funding, and/or consulting/advisory/personal fees from various sources. Dr. JP Zarate, Dr. A Ridolfi, and Dr. KR Lorenc were employed by and owned stocks in Novartis.

Source: Burris HA et al. Br J Cancer. 2021 Jun 22. doi: 10.1038/s41416-021-01415-9.

Key clinical point: The clinical benefit of ribociclib is maintained in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who required dose reduction to manage adverse events.

Major finding: Ribociclib dose reductions were reported in 45.8% of patients; most were attributed to adverse reactions. The median progression-free survival was 24.8, 24.9, and 29.6 months for patients who received 71% or less, 72%-96%, and 97%-100% ribociclib relative dose intensity, respectively. The clinical benefit ratio was 87.6%, 76.8%, and 73.6%, respectively.

Study details: A pooled analysis of MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials evaluated the safety and impact of ribociclib dose reduction in 818 patients with HR-positive, HER2-negative advanced breast cancer.

Disclosures: The study was supported by Novartis Pharmaceuticals Corporation. The authors received grants, funding, and/or consulting/advisory/personal fees from various sources. Dr. JP Zarate, Dr. A Ridolfi, and Dr. KR Lorenc were employed by and owned stocks in Novartis.

Source: Burris HA et al. Br J Cancer. 2021 Jun 22. doi: 10.1038/s41416-021-01415-9.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, CT-P6, a trastuzumab biosimilar shows 3-year survival comparable with trastuzumab.

Major finding: Median disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were not reached in either group. In the CT-P6 vs trastuzumab group, the 3-year DFS, PFS, and OS rates were 83% vs 83%, 81% vs 87%, and 93% vs 94%, respectively.

Study details: A randomized, double-blind, active-controlled, phase 3 equivalence trial of 549 patients with HER2‑positive early breast cancer who received neoadjuvant treatment with CT-P6 or trastuzumab with chemotherapy, followed by surgery. Patients were followed up for 3 years (n=528) after receiving adjuvant CT-P6 or trastuzumab.

Disclosures: The study was funded by Celltrion, Inc. The authors received grants and consulting/advisory fees from various sources. Dr. SJ Lee and Dr. S Kim were employees of and/or stockholders in Celltrion.

Source: Stebbing J et al. Breast Cancer Res Treat. 2021 Jun 20. doi: 10.1007/s10549-021-06240-5.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, CT-P6, a trastuzumab biosimilar shows 3-year survival comparable with trastuzumab.

Major finding: Median disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were not reached in either group. In the CT-P6 vs trastuzumab group, the 3-year DFS, PFS, and OS rates were 83% vs 83%, 81% vs 87%, and 93% vs 94%, respectively.

Study details: A randomized, double-blind, active-controlled, phase 3 equivalence trial of 549 patients with HER2‑positive early breast cancer who received neoadjuvant treatment with CT-P6 or trastuzumab with chemotherapy, followed by surgery. Patients were followed up for 3 years (n=528) after receiving adjuvant CT-P6 or trastuzumab.

Disclosures: The study was funded by Celltrion, Inc. The authors received grants and consulting/advisory fees from various sources. Dr. SJ Lee and Dr. S Kim were employees of and/or stockholders in Celltrion.

Source: Stebbing J et al. Breast Cancer Res Treat. 2021 Jun 20. doi: 10.1007/s10549-021-06240-5.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, CT-P6, a trastuzumab biosimilar shows 3-year survival comparable with trastuzumab.

Major finding: Median disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were not reached in either group. In the CT-P6 vs trastuzumab group, the 3-year DFS, PFS, and OS rates were 83% vs 83%, 81% vs 87%, and 93% vs 94%, respectively.

Study details: A randomized, double-blind, active-controlled, phase 3 equivalence trial of 549 patients with HER2‑positive early breast cancer who received neoadjuvant treatment with CT-P6 or trastuzumab with chemotherapy, followed by surgery. Patients were followed up for 3 years (n=528) after receiving adjuvant CT-P6 or trastuzumab.

Disclosures: The study was funded by Celltrion, Inc. The authors received grants and consulting/advisory fees from various sources. Dr. SJ Lee and Dr. S Kim were employees of and/or stockholders in Celltrion.

Source: Stebbing J et al. Breast Cancer Res Treat. 2021 Jun 20. doi: 10.1007/s10549-021-06240-5.

Key clinical point: Bisphosphonate therapy for 5 vs 2 years in patients with high-risk early breast cancer yields no added survival benefit and leads to increased risk for adverse events.

Major finding: There were no significant differences in disease-free survival (hazard ratio [HR], 0.97; P = .81), overall survival (HR, 0.98; P = .90), and distant disease-free survival (HR, 0.87; P = .38) between 5- and 2-year bisphosphonate treatment groups. The rate of adverse events was 46.2% with 5-year therapy and 27.2% with 2-year treatment.

Study details: A randomized phase 3, open-label SUCCESS A trial of 2,987 patients with high-risk early breast cancer randomly assigned to receive bisphosphonate zoledronate for either 5 or 2 years.

Disclosures: The study was supported by AstraZeneca, Chugai, Menarini Silicon Biosystems (formerly Veridex), Lilly, Novartis, and Sanofi-Aventis. The authors received honoraria, personal fees, research support, consulting fees, and travel grants from various sources.

Source: Friedl TWP et al. JAMA Oncol. 2021 Jun 24. doi: 10.1001/jamaoncol.2021.1854.

Key clinical point: Bisphosphonate therapy for 5 vs 2 years in patients with high-risk early breast cancer yields no added survival benefit and leads to increased risk for adverse events.

Major finding: There were no significant differences in disease-free survival (hazard ratio [HR], 0.97; P = .81), overall survival (HR, 0.98; P = .90), and distant disease-free survival (HR, 0.87; P = .38) between 5- and 2-year bisphosphonate treatment groups. The rate of adverse events was 46.2% with 5-year therapy and 27.2% with 2-year treatment.

Study details: A randomized phase 3, open-label SUCCESS A trial of 2,987 patients with high-risk early breast cancer randomly assigned to receive bisphosphonate zoledronate for either 5 or 2 years.

Disclosures: The study was supported by AstraZeneca, Chugai, Menarini Silicon Biosystems (formerly Veridex), Lilly, Novartis, and Sanofi-Aventis. The authors received honoraria, personal fees, research support, consulting fees, and travel grants from various sources.

Source: Friedl TWP et al. JAMA Oncol. 2021 Jun 24. doi: 10.1001/jamaoncol.2021.1854.

Key clinical point: Bisphosphonate therapy for 5 vs 2 years in patients with high-risk early breast cancer yields no added survival benefit and leads to increased risk for adverse events.

Major finding: There were no significant differences in disease-free survival (hazard ratio [HR], 0.97; P = .81), overall survival (HR, 0.98; P = .90), and distant disease-free survival (HR, 0.87; P = .38) between 5- and 2-year bisphosphonate treatment groups. The rate of adverse events was 46.2% with 5-year therapy and 27.2% with 2-year treatment.

Study details: A randomized phase 3, open-label SUCCESS A trial of 2,987 patients with high-risk early breast cancer randomly assigned to receive bisphosphonate zoledronate for either 5 or 2 years.

Disclosures: The study was supported by AstraZeneca, Chugai, Menarini Silicon Biosystems (formerly Veridex), Lilly, Novartis, and Sanofi-Aventis. The authors received honoraria, personal fees, research support, consulting fees, and travel grants from various sources.

Source: Friedl TWP et al. JAMA Oncol. 2021 Jun 24. doi: 10.1001/jamaoncol.2021.1854.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive locally recurrent or metastatic breast cancer, paclitaxel can be an alternative to docetaxel with first-line pertuzumab plus trastuzumab.

Major finding: The median follow-up was 68.7 months. The median progression-free survival was 19.4 (95% confidence interval [CI], 16.9-22.1) months in the docetaxel, 23.2 (95% CI,19.6-25.6) months in the paclitaxel, and 19.2 (95% CI, 11.7-37.1) months in the nab-paclitaxel group. Docetaxel was associated with higher rates of grade ≥3 neutropenia and febrile neutropenia.

Study details: A multicenter, open-label, single-arm phase 3b PERUSE study of 1,436 eligible patients with inoperable HER2-positive locally recurrent or metastatic breast cancer who received pertuzumab and trastuzumab with a taxane (docetaxel, paclitaxel, or nab-paclitaxel).

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The authors reported receiving research funding, personal fees, grants, honoraria, advisory/speaker/consulting fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.06.024.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive locally recurrent or metastatic breast cancer, paclitaxel can be an alternative to docetaxel with first-line pertuzumab plus trastuzumab.

Major finding: The median follow-up was 68.7 months. The median progression-free survival was 19.4 (95% confidence interval [CI], 16.9-22.1) months in the docetaxel, 23.2 (95% CI,19.6-25.6) months in the paclitaxel, and 19.2 (95% CI, 11.7-37.1) months in the nab-paclitaxel group. Docetaxel was associated with higher rates of grade ≥3 neutropenia and febrile neutropenia.

Study details: A multicenter, open-label, single-arm phase 3b PERUSE study of 1,436 eligible patients with inoperable HER2-positive locally recurrent or metastatic breast cancer who received pertuzumab and trastuzumab with a taxane (docetaxel, paclitaxel, or nab-paclitaxel).

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The authors reported receiving research funding, personal fees, grants, honoraria, advisory/speaker/consulting fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.06.024.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive locally recurrent or metastatic breast cancer, paclitaxel can be an alternative to docetaxel with first-line pertuzumab plus trastuzumab.

Major finding: The median follow-up was 68.7 months. The median progression-free survival was 19.4 (95% confidence interval [CI], 16.9-22.1) months in the docetaxel, 23.2 (95% CI,19.6-25.6) months in the paclitaxel, and 19.2 (95% CI, 11.7-37.1) months in the nab-paclitaxel group. Docetaxel was associated with higher rates of grade ≥3 neutropenia and febrile neutropenia.

Study details: A multicenter, open-label, single-arm phase 3b PERUSE study of 1,436 eligible patients with inoperable HER2-positive locally recurrent or metastatic breast cancer who received pertuzumab and trastuzumab with a taxane (docetaxel, paclitaxel, or nab-paclitaxel).

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The authors reported receiving research funding, personal fees, grants, honoraria, advisory/speaker/consulting fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.06.024.

Key clinical point: Atezolizumab plus nab-paclitaxel shows no overall survival (OS) advantage in patients with advanced/metastatic triple-negative breast cancer (TNBC) overall, but improves OS in in a patient subgroup positive for programmed death-ligand 1 (PD-L1) expression in tumor-infiltrating immune cells.

Major finding: There was no difference in OS in the intent-to-treat population (P = .077). An exploratory analysis in the PD-L1 immune cell-positive population showed OS improvement with atezolizumab plus nab-paclitaxel (stratified hazard ratio, 0.67; 95% confidence interval, 0.53-0.86).

Study details: A randomized, double-blind, placebo-controlled phase 3 IMpassion130 trial of 902 patients with advanced/metastatic TNBC who received atezolizumab plus nab-paclitaxel (n=451) or placebo plus nab-paclitaxel (n=451).

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd./Genentech, Inc. The authors received honoraria, travel support, research funding, consulting/advisory/steering committee fees, and grants from various sources. Some of the authors were employed by and/or owned stocks in Genentech/Roche.

Source: Emens LA et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.355.

Key clinical point: Atezolizumab plus nab-paclitaxel shows no overall survival (OS) advantage in patients with advanced/metastatic triple-negative breast cancer (TNBC) overall, but improves OS in in a patient subgroup positive for programmed death-ligand 1 (PD-L1) expression in tumor-infiltrating immune cells.

Major finding: There was no difference in OS in the intent-to-treat population (P = .077). An exploratory analysis in the PD-L1 immune cell-positive population showed OS improvement with atezolizumab plus nab-paclitaxel (stratified hazard ratio, 0.67; 95% confidence interval, 0.53-0.86).

Study details: A randomized, double-blind, placebo-controlled phase 3 IMpassion130 trial of 902 patients with advanced/metastatic TNBC who received atezolizumab plus nab-paclitaxel (n=451) or placebo plus nab-paclitaxel (n=451).

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd./Genentech, Inc. The authors received honoraria, travel support, research funding, consulting/advisory/steering committee fees, and grants from various sources. Some of the authors were employed by and/or owned stocks in Genentech/Roche.

Source: Emens LA et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.355.

Key clinical point: Atezolizumab plus nab-paclitaxel shows no overall survival (OS) advantage in patients with advanced/metastatic triple-negative breast cancer (TNBC) overall, but improves OS in in a patient subgroup positive for programmed death-ligand 1 (PD-L1) expression in tumor-infiltrating immune cells.

Major finding: There was no difference in OS in the intent-to-treat population (P = .077). An exploratory analysis in the PD-L1 immune cell-positive population showed OS improvement with atezolizumab plus nab-paclitaxel (stratified hazard ratio, 0.67; 95% confidence interval, 0.53-0.86).

Study details: A randomized, double-blind, placebo-controlled phase 3 IMpassion130 trial of 902 patients with advanced/metastatic TNBC who received atezolizumab plus nab-paclitaxel (n=451) or placebo plus nab-paclitaxel (n=451).

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd./Genentech, Inc. The authors received honoraria, travel support, research funding, consulting/advisory/steering committee fees, and grants from various sources. Some of the authors were employed by and/or owned stocks in Genentech/Roche.

Source: Emens LA et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.355.