Pretreated Advanced Breast Cancer Research Articles

Primary results from PATRICIA cohort C (SOLTI-1303), a randomized phase II study evaluating palbociclib with trastuzumab and endocrine therapy in pretreated HER2-positive and PAM50 luminal advanced breast cancer.

1008 Background: The PATRICIA trial (cohorts A-B) demonstrated that palbociclib plus trastuzumab (T) is safe and active in patients (pts) with T-pretreated HER2-positive Hormone Receptor-positive (HR+/HER2+) PAM50 Luminal advanced breast cancer (ABC). Here, we present the primary efficacy analysis of the randomized cohort C from the PATRICIA trial that compares the efficacy of palbociclib + T + endocrine therapy (ET) with treatment of physicians’ choice (TPC). Methods: PATRICIA (cohort C) is a randomized, open-label, phase II study conducted at 34 sites in Spain recruiting from August 2019 to August 2023. Pts with HER2+/HR+ and centrally tested PAM50 Luminal A or B intrinsic subtype ABC who had received at least one prior line of anti-HER2 based regimens were eligible. Pts were randomized 1:1 to Cohort C1 (Palbociclib 125 mg/day orally 3 weeks/1 week off + T + ET) or Cohort C2 (TPC, including T + any ET or chemotherapy (CT) + T, or T-DM1). The stratification factors were number of previous regimens for ABC and presence of visceral disease. The primary endpoint was progression-free survival (PFS). The trial was designed to recruit a total of 102 pts, having an 80% power with one-sided alpha=0.1 to detect a HR of 0.62 in favor of the palbociclib cohort. The study was closed after 73 pts were randomized due to slow recruitment. Results: At data cut-off, 264 pts were pre-screened, and 73 pts were randomized. Baseline pts characteristics are summarized in Table 1. In cohort C1, 50% of the pts received fulvestrant and 50% aromatase inhibitor as ET. In cohort C2, 37.1% of pts were treated with TDM-1, 45.7% with CT+ T, 11.4 % with ET + T and two pts withdrew their consent before starting the treatment. Palbociclib + T + ET was associated with longer PFS compared to TPC (median 9.1 vs 7.5 months, stratified HR=0.52 [95%CI 0.29-0.94]; two-sided p=0.031); 12-months PFS rates were 43.7% and 21.4%, respectively. The overall response rate was 18.9% (95% CI 8.6-35.7) in cohort C1 and 8.3% (95% CI 1.4-28.5) in cohort C2. Grade ≥3 adverse events occurred in 63.2% of pts in C1 and 45.5% in C2 cohort. The most frequent grade ≥3 adverse event in the experimental arm was neutropenia (55.3%). Conclusions: The combination of palbociclib, T and ET showed a statistically significant improvement in PFS in patients with previously treated PAM50 luminal A or B HER2+ advanced breast cancer, as compared to TPC. Clinical trial information: NCT02448420 . [Table: see text]

Abstract PO5-16-12: EFFICACY AND TOLERABILITY OF METRONOMIC CHEMOTHERAPY (mChT) WITH CYCLOPHOSPHAMIDE, METHOTREXATE AND CAPECITABINE (CMX) IN PATIENTS WITH HEAVILY PRETREATED ADVANCED BREAST CANCER. RESULTS FROM A MULTICENTER RETROSPECTIVE STUDY

Abstract BACKGROUND mChT consists on the administration of repetitive, low doses of chemotherapy drugs and represents an attractive and active therapeutic strategy in cancer patients. Beyond the traditional cytotoxic effect of each drug on tumor cells, mChT seems to play a role in the modulation of angiogenesis and immune-regulation. mChT has demonstrated promising clinical activity and low toxicity in patients with advanced breast cancer (ABC). The aim of this study is to describe the safety and efficacy of CMX in a retrospective cohort of heavily pretreated HER2-negative ABC patients. METHODS This is a multicenter, retrospective study that included patients with HER2-negative ABC who received treatment with CMX (capecitabine 500 mg thrice daily, methotrexate 2.5 mg twice a week, and cyclophosphamide 50 mg daily). Demographic data, tumor characteristics, previous therapies, efficacy, and toxicity of the CMX treatment were collected. Statistical analyses were performed with Stata v.14. For standard summary statistics, mean and range for continuous data and relative and absolute frequencies for categorical data were used while for survival analysis Kaplan Meier approach was employed. RESULTS A total of 25 patients from 4 centers in Spain treated between October 2016 and February 2023 were included in this analysis. Median age was 63 years (range: 37-87), 68% had visceral disease, and 48% had triple-negative tumors. All patients previously received a median of 5 prior lines of systemic therapy in the metastatic setting and 80% of patients had been treated with capecitabine, most of them in the metastatic scenario with a median treatment duration of 6.2 months. Dose reductions were necessary in 5 patients and 1 patient discontinued treatment due to toxicity. No grade 3-4 hand-foot syndrome or diarrhea were reported. Objective response rate was 20.8% and disease control rate was 54.2%. Median progression-free survival was 6.1 months (95% confidence interval [CI] 95%; 4.3 - 12.4) and median overall survival was 12.3 months (95% CI; 6.8 - 24.7). Neither the number of previous lines of treatment nor the prior use of capecitabine showed a negative impact on the efficacy of CMX. CONCLUSIONS CMX is an effective and well-tolerated scheme of mChT and may represent an adequate treatment option for patients with heavily pretreated HER2-negative ABC, including those patients that previously received capecitabine as single agent. These encouraging data warrant further investigation. Citation Format: Cristina Saavedra, María Gion, Alfonso Cortés, Patricia Cortez, Laia Garrigós, José Manuel Pérez-García, Gabriele Antonarelli, Javier Cortés. EFFICACY AND TOLERABILITY OF METRONOMIC CHEMOTHERAPY (mChT) WITH CYCLOPHOSPHAMIDE, METHOTREXATE AND CAPECITABINE (CMX) IN PATIENTS WITH HEAVILY PRETREATED ADVANCED BREAST CANCER. RESULTS FROM A MULTICENTER RETROSPECTIVE STUDY [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-12.

Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR-positive and HER2-negative advanced breast cancer: results from a phase Ib study.

Dalpiciclib is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary efficacy as monotherapy for pretreated advanced breast cancer (BC). To further assess dalpiciclib with endocrine therapy (ET) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC. A multicenter, open-label, phase Ib trial. Patients with locally recurrent or metastatic BC were enrolled in five cohorts. Patients without prior treatment for advanced disease (cohorts 1-2) were given dalpiciclib (125 or 150 mg) plus letrozole/anastrozole; patients who progressed after ET (cohorts 3-5) were given dalpiciclib (125, 150, or 175 mg) plus fulvestrant. Dalpiciclib was administered orally once daily in 3-weeks-on/1-week off schedule. The primary endpoint was safety. A total of 58 patients received dalpiciclib with letrozole/anastrozole and 46 received dalpiciclib with fulvestrant. No maximum tolerated dose of dalpiciclib was reached with letrozole/anastrozole or fulvestrant. Across all cohorts, 86.7%-93.8% of patients had a grade ⩾3 adverse event, with the most common being neutropenia (grade 3, 40.0% for dalpiciclib 175 mg and 61.8%-87.5% for lower doses; grade 4, 46.7% and 4.2%-20.6%, respectively) and leukopenia (grade 3, 80.0% for 175 mg and 33.3%-54.2% for lower doses; grade 4, 0% for all doses). At tested dose levels, steady-state areas under the concentration curve and peak concentration of dalpiciclib increased with dose when combined with letrozole/anastrozole and fulvestrant. Dalpiciclib at 150 mg was associated with a numerically higher objective response rate in both patients untreated for advanced disease (67.6%; 95% confidence interval (CI) 49.5-82.6) and patients progressing after ET (53.3%; 95% CI 26.6-78.7); as of July 30, 2022, the median progression-free survival with dalpiciclib 150 mg was 24.1 months (95% CI 16.9-46.0) with letrozole/anastrozole and 16.7 months (95% CI 1.9-24.1) with fulvestrant. Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile. The recommended phase III dose of dalpiciclib was 150 mg. ClinicalTrials.gov identifier: NCT03481998.

Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart (TQB2450) and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer

In our phase Ib trial (ClinialTrials.gov Identifier: NCT03855358), benmelstobart (TQB2450), a novel humanized IgG1 antibody against PD-L1, plus antiangiogenic multikinase inhibitor, anlotinib, demonstrated promising antitumor activities in pretreated triple negative breast cancer (TNBC) patients. We conducted explorative analyses of genomic biomarkers to explore the associations with treatment response and survival outcomes. Targeted next generation sequencing (NGS) was undertaken toward circulating tumor DNA (ctDNA) collected from peripheral blood samples prior to the start of treatment and after disease progression. A total of 31 patients received targeted NGS and functional driver mutations in 29 patients were analyzed. The most frequent mutations were TP53 (72%), MLL3 (28%), and PIK3CA (17%). At a blood-based tumor mutational burden (bTMB) cutoff of 6.7 mutations per megabase, patients with low bTMB showed better response to anlotinib plus TQB2450 (50% vs. 7%, P = 0.015) and gained greater PFS benefits (7.3 vs. 4.1 months, P = 0.012) than those with high bTMB. At a maximum somatic allele frequency (MSAF) cutoff of 10%, a low MSAF indicated a better objective response (43% vs. 20%) as well as a significantly longer median PFS (7.9 vs. 2.7 months, P < 0.001). Patients with both low MSAF and low bTMB showed a notably better objective response to anlotinib plus TQB2450 (70% vs. 11%, P < 0.001) and a significantly longer median PFS (11.0 vs. 2.9 months, P < 0.001) than patients with other scenarios. Our findings support future studes and validation of MSAF and the combined bTMB-MSAF classification as predictive biomarkers of immune checkpoint inhibitor-based regimens in advanced TNBC patients.

Effect of 1 H-NMR serum lipoproteins on immunotherapy response in advanced triple-negative breast cancer patients.

We previously reported the results of a phase II trial of anti-PD-1 antibody plus anti-vascular endothelial growth factor receptor 2 inhibitors and eribulin in heavily pretreated advanced triple-negative breast cancer with a favorable objective response rate (ORR) of 37.0% (NCT04303741). Here we report updated survival outcomes and serum metabolite changes of the study. Proton nuclear magnetic resonance spectroscopy was used to detect metabolite dynamics and explore biomarkers for response. We found that treatment-sensitive patients had higher very low-density lipoprotein-related metabolite expression at baseline. A lipid proteomics model consisting of six metabolites predicted ORR and progression-free survival at 6 months with area under the receiver operating characteristic curves of 0.88 and 0.87, respectively. Serum asparagine and sarcosine concentrations were significantly higher after treatment in treatment-resistant patients. In conclusion, we constructed a model consisting of six metabolites to identify patients who benefit more from the triplet treatment, and asparagine and sarcosine may be associated with treatment resistance.

Efficacy of apatinib 250 mg combined with chemotherapy in patients with pretreated advanced breast cancer in a real-world setting.

This study evaluated the efficacy and safety of apatinib (an oral small-molecule tyrosine kinase inhibitor targeting VEGFR-2) 250 mg combined with chemotherapy in patients with pretreated metastatic breast cancer in a real-world setting. A database of patients with advanced breast cancer who received apatinib between December 2016 and December 2019 in our institution was reviewed, and patients who received apatinib combined with chemotherapy were included. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR), and treatment-related toxicity were analyzed. In total, 52 evaluated patients with metastatic breast cancer previously exposed to anthracyclines or taxanes who received apatinib 250 mg combined with chemotherapy were enrolled in this study. Median PFS and OS were 4.8 (95% confidence interval [CI] = 3.2-6.4) and 15.4 months (95% CI = 9.2-21.6), respectively. The ORR and DCR were 25% and 86.5%, respectively. Median PFS for the previous line of treatment was 2.1 months (95% CI = 0.65-3.6), which was significantly shorter than that for the apatinib-chemotherapy combination (p < 0.001). No significant difference was identified in the ORR and PFS among the subgroups(subtypes, target lesion, combined regimens and treatment lines). The common toxicities related to apatinib were hypertension, hand-foot syndrome, proteinuria, and fatigue events. Apatinib 250 mg combined with chemotherapy provided favorable efficacy in patients with pretreated metastatic breast cancer regardless of molecular types and treatment lines. The toxicities of the regimen were well tolerated and manageable. This regimen could be a potential treatment option in patients with refractory pretreated metastatic breast cancers.

Real-life experience of trastuzumab deruxtecan (T-DXd) in patients with heavily pretreated HER2 positive advanced breast cancer: A retrospective single institution study.

e13035 Background: T-DXd is a HER2 antibody–drug conjugate. It improves patient outcomes and is FDA approved for the treatment of patients with Her-2 positive and Her-2 low metastatic breast cancer. However, the impact of T-DXd use in real life compared with the findings reported in clinical trials with strict inclusion criteria has rarely been assessed. We performed a real-world study to evaluate the outcomes of patients with advanced HER2+ and HER2-low expression breast cancer. Methods: We conducted a retrospective single institution study and collected the clinical and pathologic data of patients with metastatic breast cancer who were treated with T-DXd from 2019 to 2022. The primary end point, time to treatment failure (TTF) was defined as the interval from T-DXd initiation to discontinuation. We compared the TTF of T-DXd with previous lines of treatment and also report its safety and tolerability. Results: Thirty-one patients were included in this study, seventeen with HER2-low expression and fourteen with HER2 positive. Patients had received a mean of three prior lines of therapy (ranging from 1 to 13). 32.2% of patients had ≥ 5 lines of therapy prior to T-DXd. TTF was 104 days, 95% CI [58,162] in T-DXd compared with 151 days, 95% CI [119,217] in the previous line of therapy. 2 patients (6.4%) had treatment discontinuation due to adverse events (AEs) (1 patient due to grade 3 fatigue and 1 patient due to concern for ILD). 3 patients (9.6%) had treatment delay or dose reduction due to AEs. A total of 67.7% of patients (21/31) developed AEs on T-DXd. 4 (12.9%) had grade 3 or 4 AEs. Fatigue was the most common AE followed by nausea/vomiting and thrombocytopenia. A total of 17 patients had T-DXd discontinued-15 patients discontinued due to progression or death, 2 discontinued due to AEs. 9 out of 31 patients had brain metastasis. Amongst patients with brain metastases, 7 showed stable disease while on T-DXd (1 had previously progressed on tucatinib, trastuzumab, and capecitabine). In the subgroup analysis, in patients with HER2-low expression, TTF was 98 days 95% CI [41-153] with T-DXd compared with 192 days, 95% CI [84,363] in the previous line of therapy. 2 out of 14 patients developed grade 3 or 4 AEs. Fatigue was the most common AE. In HER2+ subgroups, TTF was 126 days, 95% CI [58,353] in T-DXd vs 125 days, 95% CI [106,217] in the previous line of therapy. 2 out of 17 patients developed grade 3 or 4 AEs. Conclusions: To the best of our knowledge this is the first real life retrospective study evaluating the efficacy and tolerability of T-DXd. Overall, T-DXd had acceptable efficacy and tolerable toxicity in heavily pretreated patients. T-DXd showed a good response rate in patients with active brain metastasis. Our findings are consistent with published data on T-Dxd but is limited by virtue of retrospective series.

Efficacy and safety of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in Chinese patients with pretreated HER2-positive advanced metastatic breast cancer: results from a randomized, open-label, multicenter, phase II bridging study.

Trastuzumab is the recommended first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) patients in China, but therapeutic resistance to trastuzumab and other early-line treatments is common and late-line treatment options are limited. Derived from the same murine precursor antibody, margetuximab has enhanced anti-tumor activity compared with trastuzumab and may be an effective late-line treatment. However, data regarding the use of margetuximab in pre-treated Chinese patients are scarce. This study aimed to evaluate the efficacy and safety of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in Chinese patients, and to determine whether the results are consistent with the clinical benefit of margetuximab observed in the pivotal global phase III study. In this randomized, open-label, multicenter, phase II bridging study, eligible Chinese patients pretreated with ≥2 lines of anti-HER2 therapies were randomized 1:1 by stratified block randomization to margetuximab (15 mg/kg over at least 120 minutes) or trastuzumab (6 mg/kg over at least 30 minutes), each administered intravenously once every 21-day cycle and plus chemotherapy. Disease assessment was conducted once every two treatment cycles (6 weeks ± 7 days). The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Secondary endpoints included overall survival (OS), investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR), and the incidence and severity of treatment-emergent adverse events (TEAEs). Between February 4, 2020 and February 23, 2021, 123 patients were randomized to the margetuximab (n=62) and trastuzumab (n=61) arms. Among them, 15 and 7 patients, respectively, were still on study treatment as of data cut-off (September 3, 2021). Overall, 99.2% were female, median age was 53 years old. All patients were pretreated with trastuzumab, and 83.7% and 25.2%, respectively, were pretreated with tyrosine kinase inhibitors (TKIs) and pertuzumab. Baseline characteristics were numerically balanced between arms. BICR-assessed median PFS (mPFS) was 5.5 months in the margetuximab arm and 4.1 months in the trastuzumab arm, with a hazard ratio (HR) of 0.69 [95% confidence interval (CI): 0.43-1.12], which met the consistency criterion (HR <0.88) for bridging success. Median investigator-assessed PFS was 5.5 months in the margetuximab arm and 4.0 months in the trastuzumab arm (HR =0.63; 95% CI: 0.41-0.96). Median OS (mOS) was not yet reached. Both ORR and CBR were greater in the margetuximab arm (25.5% vs. 12.5%; 32.7% vs. 14.3%). Safety results were numerically comparable between the two arms. Anti-HER2 treatment-related infusion-related reactions (IRRs) were more common in the margetuximab arm than in the trastuzumab arm (12.9% vs. 1.7%). All IRRs could be resolved. Margetuximab was effective and well-tolerated in this study, supporting its clinical use in pretreated HER2-positive MBC patients in China. ClinicalTrials.gov Identifier: NCT04262804.

A phase II study of talazoparib monotherapy in patients with wild-type BRCA1 and BRCA2 with a mutation in other homologous recombination genes

Talazoparib, a PARP inhibitor, is active in germline BRCA1 and BRCA2 (gBRCA1/2)-mutant advanced breast cancer, but its activity beyond gBRCA1/2 is poorly understood. We conducted Talazoparib Beyond BRCA (NCT02401347), an open-label phase II trial, to evaluate talazoparib in patients with pretreated advanced HER2-negative breast cancer (n = 13) or other solid tumors (n = 7) with mutations in homologous recombination (HR) pathway genes other than BRCA1 and BRCA2. In patients with breast cancer, four patients had a Response Evaluation Criteria in Solid Tumors (RECIST) partial response (overall response rate, 31%), and three additional patients had stable disease of ≥6 months (clinical benefit rate, 54%). All patients with germline mutations in PALB2(gPALB2; encoding partner and localizer of BRCA2) had treatment-associated tumor regression. Tumor or plasma circulating tumor DNA (ctDNA) HR deficiency (HRD) scores were correlated with treatment outcomes and were increased in all gPALB2 tumors. In addition, a gPALB2-associated mutational signature was associated with tumor response. Thus, talazoparib has been demonstrated to have efficacy in patients with advanced breast cancer who have gPALB2 mutations, showing activity in the context of HR pathway gene mutations beyond gBRCA1/2.

Economic evaluation of margetuximab vs. trastuzumab for pretreated ERBB2-positive advanced breast cancer in the US and China.

ObjectiveTo assess the economic evaluation of margetuximab plus chemotherapy over trastuzumab plus chemotherapy for women with pretreated ERBB2-positive advanced breast cancer in the United States (US) and China.MethodsBased on the SOPHIA trial, a three-state Markov model was developed to compare the cost and efficacy of margetuximab to trastuzumab for previously treated women with ERBB2-positive advanced breast cancer. The model inputs were derived from existing literature and the US life table. Primary outcomes included lifetime costs in US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to evaluate the impact of uncertainty.ResultsThe base case analyses demonstrated that margetuximab plus chemotherapy had an increasing cost of $68,132 and $20,540 over trastuzumab plus chemotherapy in the US and China, respectively, with a gain of 0.11 and 0.09 QALYs both favored margetuximab. The ICERs for two treatment strategies were $260,176 in the US and $630,777 in China, resulting in a poor cost-effectiveness at their respective threshold of willingness to play. One-way sensitivity analyses showed that the results to be most sensitive to the price of margetuximab and that of trastuzumab. And an 11 and 82% price reduction of margetuximab would make this regimen cost-effective in the US and China, respectively.ConclusionIn the US and China, margetuximab plus chemotherapy is not likely to be cost-effective for women with pretreated ERBB2-positive advanced breast cancer, whereas price reduction effectively improves insufficient cost-effectiveness.

Alpelisib Monotherapy for PI3K-Altered, Pretreated Advanced Breast Cancer: A Phase II Study

Alpelisib monotherapy displayed efficacy in heavily pretreated ER+ breast cancer with PIK3CA mutations. PIK3CA mutation dynamics in plasma during treatment and ESR1 mutations detected in plasma at baseline were candidate biomarkers predictive of benefit from alpelisib, highlighting the utility of ctDNA assays in this setting. This article is highlighted in the In This Issue feature, p. 2007.

HERibuline: Eribulin mesylate and Trastuzumab in pretreated HER2-positive advanced breast cancer—A report of region’s practice.

e13020 Background: Until 2020, in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC), the two first lines of metastatic treatment were well defined but after, many options were possible, most often combining targeted therapy plus chemotherapy. Eribulin mesylate is indicated for the treatment of patients with ABC previously treated by anthracycline and taxane regimens in the advanced setting. Here, we present the results of eribuline and trastuzumab (E/T) combination in HER2-positive ABC previously treated. Methods: Patients with HER2-positive ABC treated with the E/T combination from our region cancer institute were included in this retrospective study. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR) and safety. Results: Between November 2013 and July 2019, a total of 34 consecutive patients with HER2-positive ABC were included. The median number of previous lines for advanced setting was 4 (range 2-7). Patients treated by taxanes and anthracyclines represented 91% and 47% respectively; 50%, 79% and 62% were previously treated with pertuzumab, trastuzumab emtansine and lapatinib respectively. After a median follow up of 24.8 months, median PFS was 6.2 months (95% CI [3.35-7.13]) and median OS was 12.6 months (95% CI [7.13-18.56]). The ORR and CBR were 38% and 53%, respectively. No unexpected adverse event was observed. The most frequent grade 3-4 toxicity was hematologic (44.1%). Conclusions: Recently, new therapies have revolutionized the management of HER2-positive ABC and patients benefit from a prolonged overall survival associated with a maintained performance status. However, in pretreated and advanced metastatic setting, there are few scientific evidence to guide the choice of treatments. A combination of E/T could be an effective option in patients with good performance status and willing to receive treatment.

Anti-HER2 antibody inetetamab plus camrelizumab and utidelone for pretreated HER2-positive advanced breast cancer: A single-arm, multicenter, phase 2 study.

e13030 Background: Treatment options for patients with HER2-positive breast cancer after progression on two or more lines of HER2-directed therapies are scarce. Inetetamab, a novel anti-HER2 antibody, exhibits the same binding affinity to HER2 antigen and antibody-dependent cell-mediated cytotoxicity as trastuzumab. Previous studies have demonstrated the treatment potential of PD-1 inhibitor combined with HER2-targeted therapy in HER2-positive gastric or gastroesophageal junction cancer. Utidelone, a genetically engineered epothilone analogue, has shown promising efficacy in heavily pretreated metastatic breast cancer. This study aimed to investigated inetetamab plus camrelizumab (anti-PD-1 antibody) and utidelone in patients with HER2-positive recurrent or metastatic breast cancer who had progressed after at least two lines of HER2-directed therapies with trastuzumab and tyrosine kinase inhibitors (TKIs). Methods: In this phase 2 study (NCT04681287), patients received intravenous camrelizumab (200 mg once every 3 weeks), inetetamab (8 mg/kg loading dose then 6 mg/kg, day 1), and utidelone (30 mg/m2, days 1-5) until disease progression or intolerable toxicity. The primary endpoint was 3-month progression-free survival (PFS) rate according to the Response Evaluation Criteria In Solid Tumors, version 1.1. Secondary endpoints included objective response rate (ORR), PFS, overall survival, and safety. Simon’s two-stage design was adopted for this study. Results: Between April 2021 and January 2022, a total of 27 patients were enrolled. As of January 2022, 20 patients could be analyzed. The median number of previous systemic therapies for advanced disease was three. Previous HER2-targeted therapies included trastuzumab (20 [100%]), pyrotinib (17 [85%]), lapatinib (7 [35%]), pertuzumab (3 [15%]), and margetuximab (2 [10%]). The first stage required 10 patients, and 8 of them were free from progression at 3 months. The study proceeded to the second stage for another 31 patients, and the accrual is ongoing. The 3-month PFS rate in 20 patients was 75%. The ORR was 30% (6/20); one (5%) patient achieved complete response. The most common treatment-related adverse events (TRAEs) were peripheral neuropathy (19 [98%]), capillary proliferation (19 [98%]), alopecia (18 [90%]), and fatigue (7 [35%]). Grade ≥3 TRAEs included peripheral neuropathy (2 [10%]) and rash (1 [5%]). No treatment-related treatment discontinuation or deaths occurred. Conclusions: Inetetamab plus camrelizumab and utidelone showed promising efficacy and acceptable safety profile in patients with HER2-positive advanced breast cancer after progression on at least two lines of HER2-directed therapies with trastuzumab and TKIs. Clinical trial information: NCT04681287.

Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR+/HER2- advanced breast cancer: A phase Ib study.

1066 Background: Dalpiciclib (Dalp; SHR6390) is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary clinical activity as monotherapy for pretreated advanced breast cancer (ABC). Here we conducted a multicenter, phase 1b trial to further assess the safety, pharmacokinetics and efficacy of Dalp in combination with endocrine therapy (ET) in HR+/HER2- ABC. Methods: 5 cohorts of patients with HR+/HER2- locally recurrent or metastatic BC and any menopausal status were enrolled (~15 patients/combination regimen). Patients without prior treatment for ABC (cohort1/2) were given Dalp (125 or 150 mg po qd, d1-21, q4w) plus letrozole (LTZ; 2.5 mg po qd) or anastrozole (ATZ; 1 mg po qd); patients who progressed after ET (cohort 3-5) were given Dalp (125, 150, or 175 mg po qd, d1-21, q4w) plus fulvestrant (Fulv; 500 mg im, cycle 1 d1, d15, then d1 q4w). The primary endpoint was safety. The data cutoff date was Sep. 20, 2021. Results: 58 patients received Dalp plus LTZ/ATZ and 46 received Dalp plus Fulv. No maximum tolerated dose of Dalp was reached with LTZ/ATZ or Fulv. Across all cohorts, 75.0%-93.8% of patients had a grade ≥3 treatment-related adverse event (TRAE), with the most common being neutropenia (grade 3, 40.0%-87.5%; grade 4, 4.2%-46.7%) and leukopenia (grade 3, 33.3%-80.0%; grade 4, 0%; Table). Treatment-related serious AEs occurred in 2 (3.4%) patients with Dalp plus LTZ/ATZ and none with Dalp plus Fulv. At the tested dose levels, steady-state areas under the concentration curve and peak concentration of Dalp increased with dose in combination with LTZ/ATZ or Fulv. Dalp 150 mg was associated with a numerically higher objective response rate in both ET-untreated (67.6%, 95% CI 49.5-82.6) and ET-pretreated (53.3%, 95% CI 26.6-78.7) patients per investigator. The median progression-free survival with Dalp 150 mg was 20.3 mo (95% CI 16.9-not reached [NR]) and 16.7 mo (95% CI 1.9-24.1) in ET-untreated and ET-pretreated patients respectively. Conclusions: Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile, with hematological toxicities as the most common TRAEs. The recommended phase 3 dose of dalpiciclib was 150 mg. Together with the promising anti-tumor activity observed with the combination therapy in HR+/HER2- ABC, further trials are warranted. Clinical trial information: NCT03481998. [Table: see text]

Feasibility of palbociclib in women aged 70 and older with resistant and/or pretreated advanced breast cancer in the PALOMAGE study

In France, more than 1 in 3 women diagnosed with breast cancer (BC) is 70 years old or older. Given the many factors that may impact on the success of treatment in older patients with advanced BC (ABC), treatment feasibility (i.e. receiving the optimal duration of treatment) should be assessed carefully in real life. PALOMAGE is a French prospective multi-center study evaluating palbociclib (PAL) + endocrine therapy (ET) in real life setting in women aged ≥70 with hormone receptors positive (HR+) HER2- ABC, either ET-sensitive with no prior systemic treatment for ABC (cohort A), or ET-resistant (relapse during or < 1 year after the end of adjuvant ET) and/or with prior systemic treatment for ABC (cohort B). Quality of life (EORTC QLQ-C30 and ELD14) and geriatric [G8 and Geriatric-COre DatasEt (G-CODE)] data were collected. This analysis reports on the primary endpoint in cohort B: rate (with 95%CI) of permanent PAL discontinuation at 6 months (mo) for any reason including progression, toxicity, patient's choice, or death. Associations between baseline characteristics (demographic, clinical, geriatric) and discontinuation of treatment at 6 mo were estimated with appropriate statistical tests. From 10/2018 to 07/2020, 406 patients were included in cohort B with: median age 78 years (69-98) (15.8% > 85), 15.8% ECOG performance status (PS) ≥2, 67.8% abnormal G8 score (≤14), 86.7% Charlson score ≥4, 49.3% visceral metastasis (liver 25.9%, lung 27.6%), 24.4% ≥2 lines of systemic treatment for ABC, 52.4% prior chemotherapy. PAL starting dose was 125, 100 and 75 mg in 72.6%, 22.1% and 5.2% of patients, respectively, combined with fulvestrant or an aromatase inhibitor in 65.3% and 34.7%, respectively. The primary endpoint analysis was performed on the full analysis set of cohort B: among 378 eligible and treated patients, 109 (28.8%; 95%CI=24.3-33.7) had a permanent PAL discontinuation at 6 mo due to progression (67 patients/17.7%), toxicity (14 patients/3.7%), death (14 patients/3.7%), or patient's choice (11 patients/2.9%). Treatment discontinuation rate at 6 mo according to PAL starting dose 125/100/75 mg was 28% (95%CI=22.7-33.6), 30.5% (95%CI=20.8-41.6), and 35.3% (95%CI=14.2-61.7), respectively. With a median follow-up of 11.3 mo, 33.6% of patients were still on PAL treatment. Median time to treatment failure (TTF) was 11.6 mo (95%CI=10-13). The G-CODE domains at baseline that were significantly associated with PAL permanent discontinuation at 6 mo were: alteration of autonomy with ADL score ≤5 (p=0.04) and unintentional weight loss >10% in the last 6 mo (p<0.001). PALOMAGE is a unique French real-world study dedicated to older patients treated with PAL for ABC. This is one of the first studies to consider geriatric characteristics with the use of G-CODE. In this cohort B analysis, treatment discontinuation rate at 6 mo was 28.8%, close to what has been observed in PALOMA 3 study, and did not differ according to PAL starting dose. Although not controlled, these data are reassuring and suggest that PAL treatment is feasible in resistant and/or pretreated women aged ≥70. Further analyses (bivariate and multivariate) will be performed on the association between baseline characteristics and treatment discontinuation. Relation with quality of life will also be explored using time until definitive quality of life score deterioration, for example. Breast cancer; Elderly; Real world data; Palbociclib; Geriatric characteristics Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts.

Abstract P1-18-04: Feasibility of palbociclib in women aged 70 and older with resistant and/or pretreated advanced breast cancer in the PALOMAGE study

Abstract Background:In France, more than 1 in 3 women diagnosed with breast cancer (BC) is 70 years old or older. Given the many factors that may impact on the success of treatment in these older patients, especially with advanced BC (ABC), treatment feasibility (i.e. receiving the optimal duration of treatment) should be assessed carefully in real life. Methods:PALOMAGE is a French prospective study evaluating palbociclib (PAL) + endocrine therapy (ET) in real life setting in women aged ≥70 with hormone receptors positive (HR+) HER2- ABC, either ET-sensitive with no prior systemic treatment for ABC (cohort A), or ET-resistant (relapse during or &amp;lt; 1 year after the end of adjuvant ET) and/or with prior systemic treatment for ABC (cohort B). Quality of life data (EORTC QLQ-C30 and ELD14) and geriatric data [G8 and Geriatric-COre DatasEt (G-CODE)] were collected. This analysis in cohort B reports on the primary endpoint: treatment feasibility based on the rate of permanent PAL discontinuation at 6 months (mo) for any reason including progression, toxicity, patient’s choice, or death. Two-sided 95% binomial confidence interval (CI) was used. Results:From 10/2018 to 07/2020, 406 patients were included in cohort B: median age 78 years (69-98) (15.8% &amp;gt; 85), 15.8% ECOG performance status (PS) ≥2, 67.8% G8 score ≤14, 86.7% Charlson score ≥4, 49.3% visceral metastasis (liver 25.9%, lung 27.6%), 24.4% ≥2 lines of systemic treatment for ABC, 52.4% prior chemotherapy. PAL starting dose was 125, 100 and 75 mg in 72.6%, 22.1% and 5.2% of patients, respectively, combined with fulvestrant or an aromatase inhibitor in 65.3% and 34.7%, respectively.The primary endpoint analysis was performed on the full analysis set of cohort B: amongst 378 patients, 109 (28.8%; 95%CI=24.3-33.7) had a permanent PAL discontinuation at 6 mo due to progression (67 patients/17.7%), toxicity (14 patients/3.7%), death (14 patients/3.7%), or patient’s choice (11 patients/2.9%). Visceral progression was observed in 32 patients (8.5%), mainly in liver. Neutropenia (including 1 febrile neutropenia) was the main toxicity leading to PAL discontinuation. No death was considered PAL-related by investigators. Treatment discontinuation rate at 6 mo according to PAL starting dose 125/100/75 mg was 28% (95%CI=22.7-33.6), 30.5% (95%CI=20.8-41.6), and 35.3% (95%CI=14.2-61.7), respectively. With a median follow-up of 11.3 mo, 33.6% of patients were still on PAL treatment. Median time to treatment failure (TTF) was 11.6 mo (95%CI=10-13). Efficacy, safety and quality of life will be presented according to geriatric status. Conclusion:PALOMAGE is a unique French real-world study dedicated to older patients treated with PAL for ABC. In this cohort B analysis, treatment discontinuation rate at 6 mo was 28.8%, close to what has been observed in PALOMA 3 study, and did not differ according to PAL starting dose. Although not controlled, these data are reassuring and suggest that PAL treatment is feasible in resistant and/or pretreated women aged ≥70. Citation Format: Etienne Brain, Marina Pulido, Elena Paillaud, Jessica Grosjean, William Mina, Philippe Caillet, Louis Tassy, Pierre Soubeyran, Fanny Bouteiller, Nada Rifi, Jean-Michel Vauthier, Claire Falandry, Elisabeth Carola. Feasibility of palbociclib in women aged 70 and older with resistant and/or pretreated advanced breast cancer in the PALOMAGE study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-04.

Abstract P5-18-10: Mecapegfilgrastim for primary prophylaxis of neutropenia in 355 HER2+ breast cancer patients treated with neoadjuvant docetaxel in combination with trastuzumab and/or pyrotinib: Exploratory analysis from randomized, double-blind, phase 3 PHEDRA study

Abstract Background: A dose relationship may exist for both antitumor activity and toxicity of docetaxel in breast cancer (BC) patients, while 86% grade 4 neutropenia and 12% febrile neutropenia (FN) were reported when pretreated advanced breast cancer (ABC) patients received 100 mg/m2 docetaxel monotherapy without hematopoietic support. PHEDRA was a randomized, double-blind, multicenter, phase 3 study comparing the efficacy and safety of adding pyrotinib to trastuzumab and docetaxel as neoadjuvant treatment in women with HER2+ early or locally ABC (ClinicalTrials.gov: NCT03588091). We conducted this exploratory analysis to evaluate the effectiveness of mecapegfilgrastim, a long-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF), as primary prophylaxis for neoadjuvant chemotherapy-induced neutropenia in BC patients. Methods: Patients with HER2-positive early or locally ABC were randomly assigned (1:1) to pyrotinib arm receiving 4 neoadjuvant cycles of docetaxel (100 mg/m2 iv d1 q3w), trastuzumab (8 mg/kg iv, cycle 1 d1, then 6 mg/kg d1 q3w), and pyrotinib (400 mg po qd, d1-21, q3w) or placebo arm with placebo, trastuzumab and docetaxel. Per protocol, patients were required to receive a single, 6-mg fixed dose of mecapegfilgrastim on Day 2 of each cycle. Other G-CSF was permitted if mecapegfilgrastim was unavailable at the local center or patients occurred mecapegfilgrastim intolerance. The incidence of neutropenia, FN, time to first neutropenia onset, duration per neutropenia event and cumulative neutropenia duration during neoadjuvant treatment period; and the incidences of grade 3/4 neutropenia, FN and decreased WBC count in Cycle 1 to 4 (C1-4) were presented. The data cutoff date was April 30, 2021. Results: Between July 23, 2018 and January 8, 2021, 355 patients were randomized (pyrotinib arm, n=178; placebo arm, n=177). Among them, 291 (82.0%) patients received a single, 6-mg fixed dose of mecapegfilgrastim in Cycle 1 and 270 (76.1%) patients received mecapegfilgrastim in each of the 4 cycles. Grade 3/4 neutropenia was reported in 33 (18.5%) patients in the pyrotinib arm and 36 (20.3%) patients in the placebo arm. Five (2.8%) patients in the pyrotinib arm and 2 (1.1%) patients in the placebo arm developed FN (5 FN occurred in C1; 2 FN occurred in C2). Median duration of grade 3/4 neutropenia was 3 days in the pyrotinib group and 3 days in the placebo group. Median cumulative duration of grade 3/4 neutropenia was 4 days and 3 days in the pyrotinib group and the placebo group, respectively. Grade 3/4 neutropenia mainly occurred during the first cycle of treatment for both pyrotinib (13.5%) and placebo arm (15.8%), reduced in the second cycle (5.9% vs 4.0%) and thereafter (C3: 1.8% vs 3.4%; C4: 2.4% vs 1.7%). Similar trends were observed for grade 3/4 WBC count decreased in Cycle 1 to 4. No grade 4 infection occurred. Overview of neutropenia, FN and WBC count decreased was summarized in Table 1. Consistent findings were observed in 291 mecapegfilgrastim treated patients. Conclusion: The exploratory analysis demonstrated 6-mg fixed dose of mecapegfilgrastim was effective when administrated as primary prophylaxis for neoadjuvant chemotherapy-induced neutropenia, which could be considered as a new treatment option for its advantage of once-per-cycle dosing and convenient dose management. Table 1.Overview of neutropenia, febrile neutropenia and WBC count decrease during neoadjuvant treatment period.Docetaxel+Trastuzumab+Pyrotinib(N=178)Docetaxel+Trastuzumab+Placebo (N=177)All randomized patients(N=355)Neutropenia, n (%)Any grade57 (32.0)54 (30.5)111 (31.3)Grade 16 (3.4)5 (2.8)11 (3.1)Grade 218 (10.1)13 (7.3)31 (8.7)Grade 315 (8.4)20 (11.3)35 (9.9)Grade 418 (10.1)16 (9.0)34 (9.6)Median time to first onset (IQR), days7 (6-63)6 (6-49)7 (6-53)Median duration per grade 3 or higher neutropenia, days (range)3 (1-16)3 (2-12)3 (1-16)Median cumulative duration of grade 3 or higher neutropenia, days (range)4 (2-16)3 (2-14)3 (2-16)FN, n (%)5 (2.8)2 (1.1)7 (2.0)Grade 3 or higher neutropenia, n (%) *Cycle 124 (13.5)28 (15.8)52 (14.6)Cycle 210 (5.9)7 (4.0)17 (4.9)Cycle 33 (1.8)6 (3.4)9 (2.6)Cycle 44 (2.4)3 (1.7)7 (2.1)Grade 3 or higher FN, n (%) *Cycle 12 (1.1)2 (1.1)4 (1.1)Cycle 22 (1.2)02 (0.6)Cycle 3000Cycle 4000Grade 3 or higher WBC count decreased, n (%) *Cycle 120 (11.2)20 (11.3)40 (11.3)Cycle 28 (4.7)2 (1.1)10 (2.9)Cycle 32 (1.2)1 (0.6)3 (0.9)Cycle 44 (2.4)2 (1.1)6 (1.8)Note: IQR, interquartile range; FN, febrile neutropenia; WBC, white blood cell.*The denominator indicates number of patients with mecapegfilgrastim for prophylaxis use in this cycle. Citation Format: Min He, Benlong Yang, Jiong Wu, Zhenzhen Liu, Hongjian Yang, Jinhai Tang, Kun Wang, Yunjiang Liu, Haibo Wang, Peifen Fu, Shuqun Zhang, Qiang Liu, Zefei Jiang, Shusen Wang, Jian Huang, Chuan Wang, Shu Wang, Yongsheng Wang, Linlin Zhen, Xiaoyu Zhu, Shulin Liu, Ping Yan, Jianjun Zou. Mecapegfilgrastim for primary prophylaxis of neutropenia in 355 HER2+ breast cancer patients treated with neoadjuvant docetaxel in combination with trastuzumab and/or pyrotinib: Exploratory analysis from randomized, double-blind, phase 3 PHEDRA study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-10.

A New Kid on the Block: Sacituzumab Govitecan for the Treatment of Breast Cancer and Other Solid Tumors.

Human trophoblast cell-surface antigen-2 (Trop-2) is a membrane glycoprotein involved in cell proliferation and motility, frequently overexpressed in epithelial tumors. Thus, it represents an attractive target for anticancer therapies. Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate, consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolyzable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment. Indeed, unprecedented results have been observed with SG in patients with heavily pretreated advanced triple-negative breast cancer and urothelial carcinomas, and the drug has already received approval for these indications. These results are coupled with a manageable toxicity profile, with neutropenia and diarrhea as the most frequent adverse events, mainly of grades 1–2. While several trials are exploring SG activity in different tumor types and settings, potential biomarkers of response are under investigation. Among these, Trop-2 overexpression and the presence of BRCA1/2 mutations seem to be the most promising. We review the available literature concerning SG, with a focus on its toxicity spectrum and possible biomarkers of its response.

Eribulin: clinical review and new perspective in advanced breast cancer

Eribulin is a unique microtubule inhibitor with mitotic and nonmitotic mechanisms of action. Eribulin has substantial activity in patients with pretreated (anthracycline and a taxane) advanced or metastatic breast cancer was confirmed by large-scale phase III clinical trials. We review recent pharmacological and clinical findings of eribulin use in metastatic breast cancer, particularly highlighting eribulin in difficult-to-treat and aggressive disease and safety data in specific patient populations. Furthermore, recent advancements and potential future directions for its clinical usage in our understanding are discussed. Ongoing studies of eribulin in combination with immunotherapies and established cytotoxic agents may facilitate to shape the future landscape in the treatment of breast cancer.

Abstract OT-03-05: Trastuzumab deruxtecan (T-DXd; DS-8201) in combination with other anticancer agents in patients with HER2-low metastatic breast cancer: A phase 1b, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast08)

Abstract Background In patients (pts) with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) metastatic breast cancer (mBC), HER2-targeted therapies have greatly improved survival. However, for pts with HER2-low mBC (IHC 1+ or IHC 2+/ISH−), there are no approved HER2-directed therapies. In pts with hormone receptor (HR)+, HER2-low mBC whose disease progresses on standard first-line treatment (endocrine therapy [ET] and CDK4/6 inhibitors), median progression-free survival (PFS) with continued ET alone is ≈ 2 months, and with mTOR or PI3K inhibitors (in PIK3CA-mutant tumors) in the second-line setting, PFS ranges from 3.5 to 7.3 months, respectively (André F, et al. ESMO 2018; Dhakal A, at al. ASCO 2018; Rugo R, et al. ASCO 2020). For ET-refractory pts, chemotherapy (CTX) is the standard of care and has a poor benefit-risk ratio. The treatment landscape for pts with HR−, HER2-low mBC is even more limited, consisting largely of CTX (with or without PD-1/PD-L1 inhibitors in the first-line setting). T-DXd is an antibody-drug conjugate composed of a humanized HER2 antibody attached to a membrane-permeable topoisomerase I inhibitor payload via a cleavable tetrapeptide-based linker at a drug to antibody ratio of ≈ 8. In a recent phase 1b study, pts with heavily pretreated (median, 7.5 prior therapies) HER2-low advanced or metastatic breast cancer treated with T-DXd 5.4 or 6.4 mg/kg had a confirmed objective response rate (ORR) of 37.0% (20/54) by independent central review and a median PFS of 11.1 months, and the safety profile was generally manageable (Modi S, et al. J Clin Oncol. 2020;38:1887-1896). Here, we describe a phase 1b trial evaluating the safety, tolerability, and pharmacokinetics (PK) of T-DXd in combination with other anticancer agents in pts with HER2-low, HR+ or HR− mBC. Study Description DESTINY-Breast08 is a multicenter, open-label, 2-part study evaluating T-DXd combinations in pts with HER2-low mBC. The 5 treatment modules comprise T-DXd in combination with (1) capecitabine, (2) durvalumab + paclitaxel, (3) capivasertib, (4) anastrozole, and (5) fulvestrant. Part 1 (dose finding): Each treatment module will enroll 3 to 12 pts per dose level to determine the recommended phase 2 dose (RP2D) in combination; modules 1 through 3 will enroll irrespective of HR status, whereas modules 4 and 5 will be restricted to only HR+ pts. HR+ pts should have received ≥ 1 prior line of ET and ≥ 1 prior line of CTX; HR− pts should have received ≥ 1 prior line of CTX. Part 2 (dose expansion): Modules 1, 4, and 5 will enroll 20 pts, and modules 2 and 3 will enroll 40 pts using the RP2D determined in part 1 of each module. Patient eligibility per module in part 2 is as follows: Module 1 (HR+ or HR−): HR−, only 1 prior line of CTX for mBC; HR+, only 1 prior line of ET but no prior CTX for mBCModule 2 (HR−): no prior CTX for mBCModule 3 (HR−): only 1 prior line of CTX for mBCModules 4 and 5 (HR+): only 1 prior line of ET but no prior CTX for mBC The primary endpoint in part 1 is safety and tolerability and determination of RP2Ds. In part 2, the primary endpoint is safety and tolerability, and secondary endpoints include ORR, duration of response, and PFS (all by investigator assessment according to RECIST 1.1) as well as overall survival, PK, and immunogenicity. Citation Format: Komal Jhaveri, Erika Hamilton, Sherene Loi, Peter Schmid, Annie Darilay, Chen Gao, Gargi Patel, Magdalena Wrona, Fabrice Andre. Trastuzumab deruxtecan (T-DXd; DS-8201) in combination with other anticancer agents in patients with HER2-low metastatic breast cancer: A phase 1b, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast08) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-03-05.