Breast Cancer

Key clinical point: The combination of neoadjuvant immunotherapy (nIO) and chemotherapy led to significant improvements in survival outcomes and should be administered as the standard treatment in patients with stages II-III triple-negative breast cancer (TNBC).

Major finding: Patients who did vs did not receive nIO had ~40% lower odds of disease recurrence or death (event-free survival: hazard ratio [HR] 0.61; P < .001) or only death (overall survival: HR 0.62; P < 0.001).

Study details: Findings are from a meta-analysis of four randomized controlled trials including patients with stages II-III TNBC who were randomly assigned to receive either chemotherapy plus nIO or treatment without nIO.

Disclosures: This study did not disclose any funding source. Some authors declared serving in consulting or advisory roles, receiving educational or financial support, research or travel grant, research funding, speaker fees, or honoraria from, or having other ties with various sources.

Source: Cunha MT et al. Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: An extracted individual patient data and trial-level meta-analysis. Br J Cancer. 2023 (Nov 27). doi: 10.1038/s41416-023-02501-w

Key clinical point: The combination of neoadjuvant immunotherapy (nIO) and chemotherapy led to significant improvements in survival outcomes and should be administered as the standard treatment in patients with stages II-III triple-negative breast cancer (TNBC).

Major finding: Patients who did vs did not receive nIO had ~40% lower odds of disease recurrence or death (event-free survival: hazard ratio [HR] 0.61; P < .001) or only death (overall survival: HR 0.62; P < 0.001).

Study details: Findings are from a meta-analysis of four randomized controlled trials including patients with stages II-III TNBC who were randomly assigned to receive either chemotherapy plus nIO or treatment without nIO.

Disclosures: This study did not disclose any funding source. Some authors declared serving in consulting or advisory roles, receiving educational or financial support, research or travel grant, research funding, speaker fees, or honoraria from, or having other ties with various sources.

Source: Cunha MT et al. Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: An extracted individual patient data and trial-level meta-analysis. Br J Cancer. 2023 (Nov 27). doi: 10.1038/s41416-023-02501-w

Key clinical point: The combination of neoadjuvant immunotherapy (nIO) and chemotherapy led to significant improvements in survival outcomes and should be administered as the standard treatment in patients with stages II-III triple-negative breast cancer (TNBC).

Major finding: Patients who did vs did not receive nIO had ~40% lower odds of disease recurrence or death (event-free survival: hazard ratio [HR] 0.61; P < .001) or only death (overall survival: HR 0.62; P < 0.001).

Study details: Findings are from a meta-analysis of four randomized controlled trials including patients with stages II-III TNBC who were randomly assigned to receive either chemotherapy plus nIO or treatment without nIO.

Disclosures: This study did not disclose any funding source. Some authors declared serving in consulting or advisory roles, receiving educational or financial support, research or travel grant, research funding, speaker fees, or honoraria from, or having other ties with various sources.

Source: Cunha MT et al. Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: An extracted individual patient data and trial-level meta-analysis. Br J Cancer. 2023 (Nov 27). doi: 10.1038/s41416-023-02501-w

Key clinical point: Taxane + anthracycline-based chemotherapy (ATAX) vs taxane-based chemotherapy (TAX) did not increase the risk for major cardiovascular adverse events in older patients with early-stage triple-negative breast cancer (TNBC) or affect survival outcomes in those who had a cardiac event.

Major finding: The risks for acute myocardial infarction, potentially fatal arrhythmia, and cerebral vascular accident did not increase (all P > .1) and the risk for subsequent heart failure was lower in patients receiving ATAX vs TAX (odds ratio 0.63; P < .01). In patients who experienced a cardiac event, ATAX vs TAX did not worsen the survival outcomes.

Study details: This study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and included 2215 older women (age ≥ 66 years) diagnosed with early-stage TNBC who received ATAX (39.78%) or TAX (60.26%) in an adjuvant setting.

Disclosures: This study was funded by the Women’s Cancer Developmental Therapeutics Program, University of Colorado Cancer Center. The authors declared no conflicts of interest.

Source: Roy S et al. Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane  + anthracycline versus taxane-based chemotherapy regimens: A SEER-Medicare study. Eur J Cancer. 2023;196:113426 (Nov 11). doi: 10.1016/j.ejca.2023.113426

Key clinical point: Taxane + anthracycline-based chemotherapy (ATAX) vs taxane-based chemotherapy (TAX) did not increase the risk for major cardiovascular adverse events in older patients with early-stage triple-negative breast cancer (TNBC) or affect survival outcomes in those who had a cardiac event.

Major finding: The risks for acute myocardial infarction, potentially fatal arrhythmia, and cerebral vascular accident did not increase (all P > .1) and the risk for subsequent heart failure was lower in patients receiving ATAX vs TAX (odds ratio 0.63; P < .01). In patients who experienced a cardiac event, ATAX vs TAX did not worsen the survival outcomes.

Study details: This study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and included 2215 older women (age ≥ 66 years) diagnosed with early-stage TNBC who received ATAX (39.78%) or TAX (60.26%) in an adjuvant setting.

Disclosures: This study was funded by the Women’s Cancer Developmental Therapeutics Program, University of Colorado Cancer Center. The authors declared no conflicts of interest.

Source: Roy S et al. Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane  + anthracycline versus taxane-based chemotherapy regimens: A SEER-Medicare study. Eur J Cancer. 2023;196:113426 (Nov 11). doi: 10.1016/j.ejca.2023.113426

Key clinical point: Taxane + anthracycline-based chemotherapy (ATAX) vs taxane-based chemotherapy (TAX) did not increase the risk for major cardiovascular adverse events in older patients with early-stage triple-negative breast cancer (TNBC) or affect survival outcomes in those who had a cardiac event.

Major finding: The risks for acute myocardial infarction, potentially fatal arrhythmia, and cerebral vascular accident did not increase (all P > .1) and the risk for subsequent heart failure was lower in patients receiving ATAX vs TAX (odds ratio 0.63; P < .01). In patients who experienced a cardiac event, ATAX vs TAX did not worsen the survival outcomes.

Study details: This study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and included 2215 older women (age ≥ 66 years) diagnosed with early-stage TNBC who received ATAX (39.78%) or TAX (60.26%) in an adjuvant setting.

Disclosures: This study was funded by the Women’s Cancer Developmental Therapeutics Program, University of Colorado Cancer Center. The authors declared no conflicts of interest.

Source: Roy S et al. Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane  + anthracycline versus taxane-based chemotherapy regimens: A SEER-Medicare study. Eur J Cancer. 2023;196:113426 (Nov 11). doi: 10.1016/j.ejca.2023.113426

Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910

Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).

Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.

Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.

Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.

Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033

Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).

Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.

Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.

Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.

Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033

Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).

Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.

Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.

Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.

Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033

Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023. 

A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD. 

TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy

Study synopsis

Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial. 

Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results: 

• In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)

• At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent

• In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients

• In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively

• At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd

The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.

EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging

Study synopsis

The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study. 

Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate. 

The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events: 

• The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)

• The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)

• The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).

• In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment

• In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus

• In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib

Regarding efficacy:

• The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively

• The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively

Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer. 

OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities

Study synopsis

OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.

Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date: 

• Grade 3 neutropenia occurred in 55% of participants

• There were no grade 4 treatment-related adverse events and no dose-limiting toxicities

• OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study

• Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages

• Investigators observed antitumor activity, including partial responses

Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation. 

Conclusions

These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.

Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023. 

A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD. 

TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy

Study synopsis

Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial. 

Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results: 

• In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)

• At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent

• In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients

• In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively

• At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd

The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.

EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging

Study synopsis

The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study. 

Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate. 

The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events: 

• The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)

• The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)

• The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).

• In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment

• In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus

• In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib

Regarding efficacy:

• The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively

• The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively

Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer. 

OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities

Study synopsis

OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.

Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date: 

• Grade 3 neutropenia occurred in 55% of participants

• There were no grade 4 treatment-related adverse events and no dose-limiting toxicities

• OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study

• Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages

• Investigators observed antitumor activity, including partial responses

Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation. 

Conclusions

These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.

Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023. 

A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD. 

TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy

Study synopsis

Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial. 

Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results: 

• In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)

• At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent

• In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients

• In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively

• At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd

The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.

EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging

Study synopsis

The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study. 

Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate. 

The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events: 

• The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)

• The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)

• The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).

• In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment

• In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus

• In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib

Regarding efficacy:

• The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively

• The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively

Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer. 

OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities

Study synopsis

OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.

Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date: 

• Grade 3 neutropenia occurred in 55% of participants

• There were no grade 4 treatment-related adverse events and no dose-limiting toxicities

• OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study

• Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages

• Investigators observed antitumor activity, including partial responses

Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation. 

Conclusions

These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.