Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) demonstrated unprecedented efficacy in patients with pretreated HER2+ metastatic breast cancer (mBC). However, few data are available about its efficacy in routine clinical practice. In this multicenter retrospective study, we examined effectiveness and safety of T-DXd in a real-world population. METHODS: Clinico-pathological information about patients with HER2+ mBC who received T-DXd were collected from 12 Italian hospitals. HER2 status was determined locally. Patients who received at least one administration of T-DXd, as any therapy line for advanced disease were included in the analysis. The primary endpoint was real-word PFS (rwPFS). RESULTS: One hundred and forty-three patients were included. Median age was 66 (range: 37-90), and 4 men were included. Hormone receptor (HR) status was positive in 108 (75%) patients and negative in 35(25%). T-DXd was administered as first, second, third, or subsequent lines in 4 (3%), 16 (11%), 42 (29%), and 81 (57%) patients, respectively. Among 123 patients with measurable disease, the ORR was 68%, and the DCR was 93% (9 CRs, 74 PRs, and 30 SD). Nine (7%) patients had a primary resistance to T-DXd. With a median follow-up of 12 months, the median rwPFS was 16 months. RwPFS was 84%, 59%, and 39% at 6, 12, and 18 months, respectively. A favorable trend in rwPFS was reported in patients receiving T-DXd as I/II line versus further lines (17 vs. 15 months; P = .098). Any-grade toxicity was registered in 84 patients (59%). Most common adverse events (AEs) reported were nausea (33%), neutropenia (21%), and asthenia (21%). Liver toxicity and diarrhea were uncommon (5% and 1%). Severe toxicities was registered in 18% of patients, and the most frequent were neutropenia, nausea/vomiting, and ILD observed in 15, 2, and 3 patients. AEs led to dose reduction in 37 patients (26%). Dose reduction and AEs do not affect patients' response and survival outcomes. CONCLUSIONS: Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HER2+ mBC. These results are consistent with the results of known findings, and no new safety concerns were reported.

An Integrated Care Approach to Improve Well-Being in Breast Cancer Patients.

BACKGROUND: Breast cancer (BC) treatment has recently been revolutionized by the introduction of newer targeted agents, that helped tailoring therapies around the single patient. Along with increased survival rates, a careful evaluation of diet, lifestyle habits, physical activity, emotional and psychological experiences linked to the treatment journey, is now mandatory. However, a true proposal for an omnicomprehensive and "integrative" approach is still lacking in literature. METHODS: A scientific board of internationally recognized specialists throughout different disciplines designed a shared proposal of holistic approach for BC patients. RESULTS: A narrative review, containing information on BC treatment, endocrinological and diet aspects, physical activity, rehabilitation, integrative medicine, and digital narrative medicine, was developed. CONCLUSIONS: In the context of a patient-centered care, BC treatment cannot be separated from a patient's long-term follow-up and care, and an organized interdisciplinary collaboration is the future in this disease's cure, to make sure that our patients will live longer and better. TRIAL REGISTRATION: NCT05893368: New Model for Integrating Person-based Care (PbC) in the Treatment of Advanced HER2-negative Breast Cancer (PERGIQUAL). Registration date: 29th May 2023.

Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer Patients: What Is the Better Choice?

BACKGROUND: To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC). OBJECTIVES: The present study assesses, in a real-world setting, the activity of different subsequent therapies in patients who experienced a PD on palbociclib (P) + endocrine therapy (ET), to evaluate the best therapy sequence. METHODS: This is a multicenter retrospective observational study. Records of consecutive HR+/HER2- MBC patients from January 2017 to May 2019 were reviewed. The primary endpoint was the evaluation of progression-free survival (PFS) according to subsequent treatment lines after progression on P+ET. Toxicity data were also collected. RESULTS: The outcomes were analyzed in 89 MBC patients that had progressed on previous P+ET: 17 patients were on hormone therapy (HT) and 31 patients on chemotherapy (CT) as second-line treatments; seven patients were on HT and 34 on CT as third-line therapies. PFS of patients treated with HT as second-line therapy is significantly improved when compared with patients treated with CT (p=0.01). Considering third-line settings, the difference in PFS was not statistically different between HT and CT. A better outcome in terms of toxicity is observed among HT patients for both second- and third-line therapies. CONCLUSIONS: patients who were progressive on P+ET could still benefit from a subsequent ET. In patients who experienced a good efficacy from prior ET, without visceral metastatic sites, HT seems the most suitable option, when compared to CT, also in terms of safety.

Palbociclib plus letrozole induces a complete metabolic response in metastatic breast cancer patient with idiopathic thrombocytopenia.

Breast cancer is still the leading cause of cancer-related deaths among women aged 20-59 and metastatic breast cancer remains an incurable disease. The therapeutic paradigm of patients with HR-positive HER2-negative metastatic breast cancer has been expanded by the introduction of the inhibitors of cyclin-dependent kinases 4/6. Three compounds, palbociclib, ribociclib, and abemaciclib, have already been approved by the Food and Drug Administration (FDA) for use together with endocrine therapy; abemaciclib is also approved as a single agent. In the first-line setting, all three agents - together with an aromatase inhibitor (AI) - substantially prolonged progression-free survival. Hematologic toxicities are the most common adverse events associated with CDK4/6i, mainly with palbociclib and ribociclib. Due to the hematologic toxicity, the prescribing information of palbociclib (P) recommends monitoring complete blood counts before starting therapy and at the beginning of each cycle, as well as on day 15 of the first 2 cycles. However, there are no guidelines regarding the management of patients candidate to CDK4/6i who have bone marrow impairment. Neutropenia frequently occurs during the treatment with P, whereas thrombocytopenia represents a rare event. We here report a case of a 60-year-old woman with idiopathic thrombocytopenia treated with P plus letrozole, who presented a metabolic complete response.

Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report.

Under therapeutic pressure aggressive tumors evolve rapidly. Herein, a luminal B/HER2-low breast cancer was tracked for >3 years during a total of 6 largely unsuccessful therapy lines, from adjuvant to advanced settings. Targeted next generation sequencing (NGS) of the primary lesion, two metastases and 14 blood drawings suggested a striking, unprecedented coexistence of three evolution modes: punctuated, branched and convergent. Punctuated evolution of the trunk was supported by en bloc inheritance of a large set (19 distinct genes) of copy number alterations. Branched evolution was supported by the distribution of site-specific SNVs. Convergent evolution was characterized by a unique asynchronous expansion of three actionable (OncoKB level 3A) mutations at two consecutive ESR1 codons. Low or undetectable in all the sampled tumor tissues, ESR1 mutations expanded rapidly in blood during HER2/hormone double-blockade, and predicted life-threatening local progression at lung and liver metastatic foci. Dramatic clinical response to Fulvestrant (assigned off-label exclusively based on liquid biopsy) was associated with clearance of all 3 subclones and was in stark contrast to the poor therapeutic efficacy reported in large liquid biopsy-informed interventional trials. Altogether, deconvolution of the tumor phylogenetic tree, as shown herein, may help to customize treatment in breast cancers that rapidly develop refractoriness to multiple drugs.

Oligometastatic Breast Cancer: How to Manage It?

Breast cancer (BC) is the most frequent cancer among women and represents the second leading cause of cancer-specific death. A subset of patients with metastatic breast cancer (MBC) presents limited disease, termed 'oligometastatic' breast cancer (OMBC). The oligometastatic disease can be managed with different treatment strategies to achieve long-term remission and eventually cure. Several approaches are possible to cure the oligometastatic disease: locoregional treatments of the primary tumor and of all the metastatic sites, such as surgery and radiotherapy; systemic treatment, including target-therapy or immunotherapy, according to the biological status of the primary tumor and/or of the metastases; or the combination of these approaches. Encouraging results involve local ablative options, but these trials are limited by being retrospective and affected by selection bias. Systemic therapy, e.g., the use of CDK4/6 inhibitors for hormone receptor-positive (HR+)/HER-2 negative BC, leads to an increase of progression-free survival (PFS) and overall survival (OS) in all the subgroups, with favorable toxicity. Regardless of the lack of substantial data, this subset of patients could be treated with curative intent; the appropriate candidates could be mostly young women, for whom a multidisciplinary aggressive approach appears suitable. We provide a global perspective on the current treatment paradigms of OMBC.

The first report on coronavirus disease 2019 (COVID-19) vaccine refusal by patients with solid cancer in Italy: Early data from a single-institute survey.

INTRODUCTION: Patients with cancer have an increased risk of complications from coronavirus disease 2019 (COVID-19) infection, including death, and thus, they were considered as high-priority subjects for COVID-19 vaccination. We report on the compliance with the COVID-19 vaccine of patients affected by solid tumours. MATERIALS AND METHODS: Patients with cancer afferent to Medical Oncology 1 Unit of Regina Elena National Cancer Institute in Rome were considered eligible for vaccination if they were receiving systemic immunosuppressive antitumor treatment or received it in the last 6 months or having an uncontrolled advanced disease. The Pfizer BNT162b2 vaccine was proposed to all candidates via phone or during a scheduled visit. The reasons for refusal were collected by administrating a 6-item multiple-choice questionnaire. RESULTS: From 1st March to 20th March 2021, of 914 eligible patients, 102 refused vaccination (11.2%, 95% confidence interval [CI] 9.1-13.2). The most frequent (>10%) reasons reported were concerns about vaccine-related adverse events (48.1%), negative interaction with concomitant antitumor therapy (26.7%), and the fear of allergic reaction (10.7%). The refusal rate (RR) after 15th March (date of AstraZeneca-AZD1222 suspension) was more than doubled compared with the RR observed before (19.7% versus 8.6%, odds ratio [OR] 2.60, 95% CI 1.69-3.99; P < 0.0001). ECOG-PS 2 was associated with higher RR compared with ECOG-PS 0-1 (OR 2.94, 95% CI 1.04-8.34; P = 0.04). No statistically significant differences in RR according to other clinical characteristics were found. CONCLUSIONS: Our experience represents the first worldwide report on the adherence of patients with cancer to COVID-19 vaccination and underlines how regulatory decisions and media news spreading could influence the success of the campaign.

Immunogenicity and Safety of COVID-19 Vaccine BNT162b2 for Patients with Solid Cancer: A Large Cohort Prospective Study from a Single Institution.

PURPOSE: We assessed the immunogenicity and safety of the BNT162b2 vaccine in a large cohort of patients with cancer (CP). EXPERIMENTAL DESIGN: From March 1, 2021 to March 20, 2021, this prospective cohort study included 816 CP afferent to our institution and eligible for the vaccination. A cohort of 274 health care workers (HCW) was used as age- and sex-matched control group. BNT162b2 was administered as a two-dose regimen given 21 days apart. Blood samples to analyze anti-Spike (S) IgG antibodies (Ab) were collected prevaccination [timepoint (TP) 0], and at 3 weeks (TP1) and 7 weeks (TP2) after the first dose. RESULTS: Patients characteristics: median age 62 (range, 21-97); breast/lung cancer/others (31/21/48%); active treatment/follow-up (90/10%). In the whole CP cohort, the serologic response rate (RR) and the titre of anti-S IgG significantly increased across the TPs; at TP2, the responders (IgG >15 AU/mL) were 94.2%. Active chemotherapy and chronic use of steroids were independent predictors of lower RR. Adverse events (AE) after the booster predicted higher likelihood of response (OR, 4.04; 95% confidence interval, 1.63-9.99; P = 0.003). Comparing the matched cohorts, the responders were significantly lower in CP than in HCW at TP1 (61.2% vs. 93.2%) and TP2 (93.3% vs. 100%), while the geometric mean concentration of IgG did not significantly differ at TP2 being significantly lower in CP (23.3) than in HCW (52.1) at TP1. BNT162b2 was well tolerated in CP; severe-grade AEs were 3.5% and 1.3% after the first and second doses, respectively. CONCLUSIONS: BNT162b2 assures serologic immunization without clinically significant toxicity in CP. The second dose is needed to reach a satisfactory humoral response.