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Background: Human epidermal growth factor receptor 2 protein (HER2)- positive (+) metastatic breast cancer (MBC) is an aggressive disease and patients often undergo multiple lines of therapy following HER2 targeted therapies. The most recent National Comprehensive Cancer Network (NCCN) guidelines recommend margetuximab plus chemotherapy as fourth-line or later therapy for HER2+/hormone receptor (HR) + or negative (–) MBC. The aim of this case series is to provide information regarding margetuximab utilization in clinical practice as later-line therapy in women with HER2+ MBC. Case summaries: Margetuximab plus chemotherapy was used as fourth- or later-line treatment in patients who had received multiple HER2-targeted agents, including trastuzumab, pertuzumab, ado-trastuzumab emtansine, trastuzumab deruxtecan, tucatinib, and neratinib. Patients responded to margetuximab plus chemotherapy with real-world progression-free survival (PFS) of 3, 4, and 7 months. Conclusion: Clinical outcomes from three heavily pretreated patients with metastatic HER2+/HR+ MBC demonstrated that margetuximab plus chemotherapy resulted in real-world PFS comparable to that reported in the controlled pivotal clinical trial and support use of this targeted therapy option in appropriately identified patients. [ABSTRACT FROM AUTHOR]

Neoplastic meningitis (NM), also known as leptomeningeal carcinomatosis, is characterized by the infiltration of tumor cells into the meninges, and poses a significant therapeutic challenge owing to its aggressive nature and limited treatment options. Breast cancer is a common cause of NM among solid tumors, further highlighting the urgent need to explore effective therapeutic strategies. This review aims to provide insights into the evolving landscape of NM therapy in breast cancer by collating existing research, evaluating current treatments, and identifying potential emerging therapeutic options. This review explores the clinical features, therapeutic strategies, recent advances, and challenges of managing NM in patients with breast cancer. Its management includes multimodal strategies, including systemic and intrathecal chemotherapy, radiation therapy, and supportive care. This review also emphasizes targeted drug options and optimal drug concentrations, and discusses emerging therapies. Additionally, it highlights the variability in treatment outcomes and the potential of combination regimens to effectively manage NM in breast cancer. Challenges in treating NM include debates over clinical trial end points and the management of adverse effects. Drug resistance and low response rates are significant hurdles, particularly inHER2-negative breast cancer. The development of more precise and cost-effective medications with improved selectivity is crucial. Additionally, global efforts are needed for infrastructure development and cancer control considering the diverse nature of the disease. [ABSTRACT FROM AUTHOR]

Background Talazoparib is a poly (adenosine diphosphate-ribose) polymerase inhibitor approved for the treatment of adult patients with deleterious or suspected deleterious germline BRCA -mutated (g BRCA m), HER2-negative, locally advanced or metastatic breast cancer (LA/mBC), with approval based on the EMBRACA trial. To date, there are no published data on talazoparib use in the real-world United States (USA) setting. Patients and Methods Characteristics, treatment patterns, and clinical outcomes of real-world US patients with g BRCA m HER2-negative LA/mBC treated with talazoparib monotherapy were collected via retrospective chart review and summarized using descriptive statistics. Results Among 84 eligible patients, 35.7% had hormone receptor-positive tumors and 64.3% had triple-negative LA/mBC (TNBC). At talazoparib initiation, 29.8% had ECOG PS of ≥2 and 19.0% had brain metastasis. Mutations in g BRCA1 or 2 were detected among 64.3% and 35.7% of patients, respectively. Talazoparib was given as 1st-line therapy in 14.3% of patients, 2nd-line in 40.5%, and 3rd- or 4th-line in 45.2%. Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9), the median time from initiation to chemotherapy was 12.2 months (95% CI, 10.5-20.1), and the overall response rate was 63.1%. No differences in clinical outcomes were observed between patients with HR-positive/HER2-negative LA/mBC and patients with TNBC by using unadjusted statistical comparisons. Brain metastasis and ECOG PS ≥2 at talazoparib initiation were associated with treatment failure and progression or mortality. Conclusion Overall, talazoparib clinical outcomes in this real-world population are consistent with findings from EMBRACA. [ABSTRACT FROM AUTHOR]

The treatment of human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) has evolved dramatically since the introduction of the first targeted therapy in 1998. There are now multiple agents which can be used to prolong survival in this incurable disease state. [ABSTRACT FROM AUTHOR]

Previous analyses from the PALOMA-2 and PALOMA-3 studies showed that palbociclib (PAL) plus endocrine therapy (ET) prolongs time to first subsequent chemotherapy (TTC) versus placebo (PBO) plus ET in the overall population of patients with hormone receptor‒positive/human epidermal growth factor receptor 2‒negative (HR+/HER2−) advanced breast cancer (ABC). Here, we evaluated TTC in relevant patient subgroups. These post hoc analyses evaluated TTC by subgroup using data from 2 randomized, phase 3 studies of women with HR+/HER2− ABC. In PALOMA-2, postmenopausal patients previously untreated for ABC were randomized 2:1 to receive PAL (125 mg/day, 3/1-week schedule) plus letrozole (LET; 2.5 mg/day; n = 444) or PBO plus LET (n = 222). In PALOMA-3, premenopausal or postmenopausal patients whose disease had progressed after prior ET were randomized 2:1 to receive PAL (125 mg/day, 3/1-week schedule) plus fulvestrant (FUL; 500 mg; n = 347) or PBO plus FUL (n = 174). First subsequent chemotherapy was received by 35.5% and 56.2% in PALOMA-2 and PALOMA-3 after progression on palbociclib plus ET or placebo plus ET. Across all subgroups analyzed, the median progression-free survival (PFS) was longer in the PAL plus ET arm than the PBO plus ET arm. TTC was longer with PAL plus ET versus PBO plus ET across the same patient subgroups in both studies. Across all subgroups, PAL plus ET versus PBO plus ET had longer median PFS and resulted in prolonged TTC in both the PALOMA-2 and PALOMA-3 studies. Pfizer Inc (NCT01740427, NCT01942135). • Palbociclib + endocrine therapy prolongs time to chemotherapy in HR+/HER2– cancer. • We analyzed palbociclib efficacy data from 2 clinical trials across subgroups. • Patient subgroups were based on demographics and baseline disease characteristics. • Palbociclib increased progression-free survival versus placebo across all subgroups. • Palbociclib increased time to chemotherapy versus placebo across all subgroups. [ABSTRACT FROM AUTHOR]

Current guidelines for the treatment of human epidermal growth factor receptor 2‒negative (HER2−) advanced breast cancer (ABC) are informed by tumor characteristics and include platinum- and non–platinum-based chemotherapy, chemotherapy plus immunotherapy, endocrine monotherapy, or endocrine therapy plus a targeted therapy. In addition, poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have recently demonstrated improved clinical and patient-reported outcomes and manageable toxicity profiles compared with chemotherapy in patients with germline breast cancer susceptibility gene 1 or 2 (g BRCA1/ 2)‒mutated HER2− ABC in clinical trials and are now approved to treat this patient population. This study provides complementary real-world data regarding treatment patterns, adverse events, and physician-reported treatment satisfaction in this population. This retrospective analysis using the Adelphi Real World ABC Disease Specific Programme in the United States, European Union, and Israel included patients aged ≥18 years receiving therapy for stage IIIb or IV g BRCA1/ 2-mutated HER2− ABC. Oncologists completed a patient record form detailing patient demographics, clinical assessments, and treatment history and a survey regarding their use of and satisfaction with treatments. Among the 543 patients, mean age was 55 years, 25% were premenopausal, 70% had hormone receptor‒positive (HR+) ABC, and 30% had triple-negative breast cancer (TNBC). PARPi were used in 5%, 11%, and 12% of first-line, second-line, and third-line therapies, respectively, for patients with HR+ ABC; for TNBC, percentages were 18%, 44%, and 36%. Across treatment lines, neutropenia, anemia, and nausea occurred in 16%, 24%, and 32% of patients receiving PARPi, respectively; 22%, 38%, and 33% of patients receiving platinum chemotherapy; and 20%, 20%, and 33% of patients receiving non–platinum-based chemotherapy. Physician satisfaction was highest with PARPi and with chemotherapy plus immunotherapy. Findings in this real-world population complement clinical trial observations and provide further support for treatment of patients with PARPi in g BRCA1/2 -mutated HER2− ABC. • Treatments were evaluated in germline BRCA1/2 -mutated HER2− breast cancer patients. • Physician-reported treatment patterns demonstrated PARPi use in this population. • Nausea and anemia were the most common adverse events in those receiving PARPi. • Physician satisfaction was highest with PARPi and chemotherapy plus immunotherapy. • These real-world findings lend further support for PARPi use in this population. [ABSTRACT FROM AUTHOR]

Simple Summary: Poly(adenosine diphosphate-ribose) polymerase inhibitors have recently been shown to be effective for patients with human epidermal growth factor receptor 2—negative (HER2−) advanced breast cancer (ABC) who have a germline mutation in their breast cancer susceptibility gene 1 or 2 (BRCA1/2mut). This study evaluated differences in patient demographics, clinical characteristics, and BRCA1/2mut testing within the United States (US), European Union 4 (EU4; France, Germany, Italy, and Spain), and Israel in a real-world patient population with HER2− ABC. In the US, EU4, and Israel, 73%, 42%, and 99% of patients were tested for BRCA1/2mut, respectively. In the US and the EU4, patients who were not tested versus tested for BRCA1/2mut were more likely to have hormone receptor–positive (HR+)/HER2− ABC than triple-negative breast cancer, less likely to have a known family history of BRCA1/2-related cancer and were older. Efforts should be made to improve BRCA1/2 testing rates in the US and Europe. Poly(adenosine diphosphate-ribose) polymerase inhibitors are approved to treat patients harboring a germline breast cancer susceptibility gene 1 or 2 mutation (BRCA1/2mut) with human epidermal growth factor receptor 2—negative (HER2−) advanced breast cancer (ABC). This study evaluated differences in patient demographics, clinical characteristics, and BRCA1/2mut testing within the United States (US), European Union 4 (EU4; France, Germany, Italy, and Spain), and Israel in a real-world population of patients with HER2− ABC. Oncologists provided chart data from eligible patients from October 2019 through March 2020. In the US, EU4, and Israel, 73%, 42%, and 99% of patients were tested for BRCA1/2mut, respectively. In the US and the EU4, patients who were not tested versus tested for BRCA1/2mut were more likely to have hormone receptor—positive (HR+)/HER2− ABC (US, 94% vs. 74%, p < 0.001; EU4, 96% vs. 78%, p < 0.001), less likely to have a known family history of BRCA1/2-related cancer (US, 6% vs. 19%, p = 0.002; EU4, 10% vs. 28%, p < 0.001), and were older (US, 68.9 vs. 62.5 years, p < 0.001; EU4, 66.7 vs. 58.0 years, p < 0.001). Among tested patients, genetic counseling was received by 45%, 53%, and 98% with triple-negative breast cancer, and 36%, 36%, and 98% with HR+/HER2− ABC in the US, EU4, and Israel, respectively. Efforts should be made to improve BRCA1/2 testing rates in the US and Europe. [ABSTRACT FROM AUTHOR]

In the PALOMA-2 trial, palbociclib in combination with letrozole prolonged progression-free survival (PFS) and exhibited an acceptable safety profile in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ABC). This post hoc analysis of PALOMA-2 evaluated the efficacy and safety of palbociclib plus letrozole in patients with preexisting conditions grouped by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Postmenopausal patients without prior treatment for ABC were randomized 2:1 to receive palbociclib (125 mg/d on a 3 weeks on/1 week off schedule) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. Patients were grouped by the following MedDRA SOC preexisting conditions: gastrointestinal, musculoskeletal, metabolic, and vascular/cardiac. Median PFS was estimated by the Kaplan-Meier method, and treatment emergent adverse events (AEs) were compared between treatment arms within each preexisting condition subgroup. At baseline, 276 (41.4 %) patients had preexisting gastrointestinal disorders, 390 (58.6 %) had musculoskeletal disorders, 259 (38.9 %) had metabolic disorders, and 382 (57.4 %) had vascular/cardiac disorders. Baseline characteristics were similar between subgroups and between each arm within subgroups. Regardless of baseline preexisting condition, palbociclib plus letrozole prolonged PFS compared with placebo plus letrozole. Treatment-emergent AEs associated with palbociclib plus letrozole and dose modifications due to AEs were similar across preexisting condition subgroups. This post hoc analysis of PALOMA-2 demonstrated a favorable effect of palbociclib on PFS and a safety profile consistent with previous observations, regardless of underlying preexisting condition. Pfizer Inc (NCT01740427). • Preexisting conditions can affect the safety and efficacy of breast cancer therapies. • This is a post hoc analysis of patients with preexisting conditions from PALOMA-2. • Palbociclib prolonged median PFS, regardless of preexisting condition. • Within each treatment arm, AEs were similar regardless of preexisting condition. [ABSTRACT FROM AUTHOR]

Background: In July 2019, bevacizumab-awwb and trastuzumab-anns were marketed in the USA as the first therapeutic oncology biosimilars. We aimed to investigate the initial real-world use of bevacizumab-awwb and trastuzumab-anns for cancer management in US oncology practices. Methods: A retrospective, observational analysis of data from US cancer patients (⩾18 years of age) was carried out to describe the use of bevacizumab-awwb and trastuzumab-anns during the first 12 months following their market entry, using structured data from the Flatiron Health electronic health record-derived database. Results: A total of 2952 and 2997 patients with recorded use of bevacizumab-awwb and trastuzumab-anns, respectively, were included in the analysis. The first use of bevacizumab-awwb and trastuzumab-anns was in a patient with metastatic colorectal cancer (mCRC) within 10 days of market availability and in a patient with early stage breast cancer (eBC) within 4 days, respectively. The use of these biosimilars was observed across all approved cancer indications; 68% of bevacizumab-awwb users were those diagnosed with mCRC and 72% of trastuzumab-anns users were those diagnosed with eBC. Approximately half the patients were previously exposed to reference product (RP) prior to initiation of bevacizumab-awwb or trastuzumab-anns. Among pre-exposed patients, the majority received the biosimilars [bevacizumab-awwb (63–85%) or trastuzumab-anns (75–81%)] within 28 days of the last infusion of the RP. For both biosimilars, no major differences were observed in patient characteristics between RP-naïve and pre-exposed patients. Conclusion: Initial evidence from the first 12 months following market entry suggests rapid clinical adoption of bevacizumab-awwb and trastuzumab-anns across all approved tumor types. Usage of these two biosimilars was observed in both RP-naïve patients and patients who were previously treated with RP, with no distinctive differences in patient characteristics between the two groups. A video abstract is available for this article as part of the Kanjintionline supplemental material. [ABSTRACT FROM AUTHOR]

The use of genomic testing is rapidly emerging as an important clinical tool both for cancer diagnosis and for guiding treatment decisions in a wide range of malignancies, including gastrointestinal (GI) cancers such as colorectal cancer (CRC). Advances in technologies such as polymerase chain reaction and next‐generation sequencing methods have made it possible to noninvasively screen for CRC through, for example, the use of blood‐ or stool‐based testing, with high specificity. Tests are also available that can provide prognostic information beyond traditional clinicopathologic factors such as tumor size, grade, and nodal status, which can enable clinicians to more accurately risk stratify patients for recurrence. Lastly, in the setting of resected CRC, tests are now available that can detect circulating tumor DNA as a means for noninvasive minimal/molecular residual disease monitoring, thereby potentially guiding the use of adjuvant chemotherapy and/or escalating or de‐escalating therapy. The Gastrointestinal Cancer Therapy Expert Group (GICTEG) recently convened a virtual meeting to discuss current issues related to genomic testing in GI cancer, with the goal of providing guidance on the use of these tests for the practicing community oncologist, for whom GI cancer may be only one of many tumor types encountered. This article provides a summary of the discussion and highlights the key opinions of the GICTEG on this topic. Implications for Practice: The Gastrointestinal Cancer Therapy Expert Group seeks to provide practical guidance and opinion on the treatment of gastrointestinal malignancies, including colorectal cancer (CRC), for the practicing community oncologist in situations for which guidelines from established bodies, such as the National Comprehensive Cancer Network and the American Society of Clinical Oncology, may be less clear. In the present report, clinical guidance on the use of molecular assays for a range of clinical indications in CRC is presented, including the use of circulating tumor DNA to detect minimal/molecular residual disease in patients with successfully resected early‐stage CRC. The Gastrointestinal Cancer Therapy Expert Group (GICTEG) recently convened a virtual meeting to discuss current issues related to genomic testing in gastrointestinal cancer, with the goal of providing guidance on the use of these tests for the practicing community oncologist. This article provides a summary of the discussion and highlights the key opinions of the GICTEG on this topic. [ABSTRACT FROM AUTHOR]

This is a summary of an article that reported results of a study using data from two phase 3 clinical trials called "PALOMA-2" and "PALOMA-3." Both PALOMA-2 and PALOMA-3 trials included women with HR+/HER2− advanced breast cancer. HR+/HER2− breast cancer means the breast cancer cells of these women have receptors for female sex hormones and little or no HER2 receptors. Both PALOMA trials tested the effect of adding a medication called palbociclib (brand name, Ibrance®) to a hormone therapy. Hormone therapy, also known as endocrine therapy, is a treatment that blocks or removes hormones that cause cancer cells to grow and divide. In both trials, women took endocrine therapy with either palbociclib or a placebo. The researchers aimed to see if the results from the PALOMA trials were similar for subgroups of women in the 2 trials. The subgroups in the study included women who shared certain features about their cancer or treatment history, for example, women whose cancer had spread to the liver. For each subgroup, the study compared the results from the 2 treatment groups: (1) women who took palbociclib plus endocrine therapy, and (2) women who took placebo plus endocrine therapy. The same effect was found in all subgroups. Compared with those who took placebo, women who took palbociclib lived longer without their cancer getting worse (growing or spreading). Also, among women who had chemotherapy after stopping the trial treatment, those who took palbociclib started chemotherapy later than those who took placebo. Because palbociclib slows cancer growth and leads to tumor shrinkage, this may have played a part in starting chemotherapy later. These results show that palbociclib plus endocrine therapy is better at slowing the progression of advanced HR+/HER2− breast cancer than endocrine therapy alone. This can be said for women with different advanced HR+/HER2− breast cancer features and treatment history. Overall, the results support women taking palbociclib with an endocrine therapy if they have advanced HR+/HER2− breast cancer. [ABSTRACT FROM AUTHOR]

The article focuses on the role for fulvestrant monotherapy in the first‐line treatment of receptor–positive (ER+) metastatic breast cancer. It mentions about the combination hormonal strategies with the hope these approaches would result in longer durations of control on this treatment. It also mentions that preclinical and clinical data suggest a dose‐response effect for fulvestrant.

Purpose: To provide an overview of clinical data supporting the use of cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), metastatic breast cancer (mBC), from the perspective of the practicing oncologist community.Methods: A recent roundtable discussion was convened by The Breast Cancer Therapy Expert Group (BCTEG) to review existing data on this topic and its impact on their current practice.Results: Level 1 evidence now supports use of a CDK 4/6 inhibitor in combination with endocrine therapy for patients with HR+, HER2−, mBC. Currently, there are no biomarkers that reliably define patients who will, or will not, benefit from the addition of a CDK 4/6 inhibitor to their endocrine therapy. Additional research is needed to identify the optimal sequencing of CDK 4/6 inhibitors in relation to other therapies as well as the optimal duration of therapy; at present, evidence suggests that use in the upfront setting is better than waiting for a later line of therapy, or adding after endocrine therapy has started.Conclusions: Thus far, three CDK 4/6 inhibitors—palbociclib, ribociclib, and more recently, abemaciclib—have been approved for use in the setting of HR+, HER2−, mBC.  The degrees to which these agents differ in terms of CDK4/6 affinity, side-effect profiles, dosing, degree of central nervous system (CNS) penetration, optimal use in combination with antiestrogen therapy, and across other subsets of breast cancer, remain an active area of investigation. [ABSTRACT FROM AUTHOR]

HER2-positive breast cancer accounts for 15% to 20% of breast cancers. Before the use of trastuzumab patients with HER2-positive disease had worse outcomes than patients with HER2-negative disease. The outcomes of these patients have changed dramatically since HER2-directed therapy became available. In this manuscript, we review the current evidence on adjuvant HER2-targeted therapy for breast cancer. We describe the trials that lead to the approval of trastuzumab in this setting. These pivotal trials not only showed improvement in disease-free survival but also in overall survival. We discuss the trials examining duration of therapy, describe the evidence for the use of trastuzumab in small tumors (≤ 2 cm) and discuss the data for nonanthracycline-containing regimens. We evaluate the current evidence for the use of dual HER2 blockade with the addition of pertuzumab or lapatinib. We summarize the attempts to include bevacizumab and recently updated 5-year positive data on sequential neratinib in this setting. We outline the ongoing trials and future directions, including studies that are investigating the use of ado trastuzumab emtansine for smaller tumors, or for those with residual disease post completion of neoadjuvant therapy. Finally we describe the trial that is evaluating the benefit of trastuzumab in patients who are "HER2-low." While the outcomes of these patients have tremendously improved over the past 2 decades, future research will help us identify which patients would benefit the most from HER2-directed therapy and allow us to exclude patients who do not need, or are unlikely to benefit, from these costly interventions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our original paper, published in 1992, reported a median overall survival after first relapse in breast cancer of 26 months. The current retrospective review concentrates more specifically on patients with first systemic relapse, recognizing that subsets of patients with local recurrence are potentially curable. METHODS: Records of 5,168 patients from a largely breast-cancer-specific oncology practice were reviewed to identify breast cancer patients with their first relapse between 1996 and 2006 after primary treatment. There were 189 patients diagnosed with metastatic disease within 2 months of being seen by our therapeutic team and 101 patients diagnosed with metastatic disease greater than 2 months. The patients were divided in order to account for lead-time bias than could potentially confound the analysis of the latter 101 patients. RESULTS: Median survival for our primary study population of 189 patients was 33 months. As expected, the median survival from first systemic relapse (MSFSR) for the 101 patients excluded because of the potential for lead-time bias was better at 46 months. Factors influencing prognosis included estrogen receptor (ER) status, disease-free interval (DFI), and dominant site of metastasis. Compared with our original series, even with elimination of localregional recurrences in our present series, the median survival from first relapse has improved by 7 months over the past two decades. CONCLUSION: The new benchmark for MSFSR approaches 3 years. [ABSTRACT FROM AUTHOR]