Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study.

BACKGROUND: Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer. METHODS: PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II-III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients were randomly assigned (1:1) in permuted blocks of random size (4 or 6), stratified by anatomic stage, previous chemotherapy, age, and geographical region, by use of central telephone-based and web-based interactive response technology, to receive either 2 years of palbociclib (125 mg orally once daily on days 1-21 of a 28-day cycle) with ongoing standard provider or patient-choice adjuvant endocrine therapy (tamoxifen or aromatase inhibitor, with or without concurrent luteinising hormone-releasing hormone agonist), or endocrine therapy alone, without masking. The primary endpoint of the study was invasive disease-free survival in the intention-to-treat population. Safety was assessed in all randomly assigned patients who started palbociclib or endocrine therapy. This report presents results from the second pre-planned interim analysis triggered on Jan 9, 2020, when 67% of the total number of expected invasive disease-free survival events had been observed. The trial is registered with ClinicalTrials.gov (NCT02513394) and EudraCT (2014-005181-30). FINDINGS: Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877). At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9-29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone had invasive disease-free survival events. 3-year invasive disease-free survival was 88·2% (95% CI 85·2-90·6) for palbociclib plus endocrine therapy and 88·5% (85·8-90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76-1·15]; log-rank p=0·51). As the test statistic comparing invasive disease-free survival between groups crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. The most common grade 3-4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths. INTERPRETATION: At the planned second interim analysis, addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing. FUNDING: Pfizer.

Combining Wire Localization of Clipped Nodes with Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer: Preliminary Results from a Prospective Study.

BACKGROUND: The ideal technique for lymph node staging for patients with pathologically confirmed node-positive breast cancer at diagnosis and neoadjuvant chemotherapy (NAC) is unclear. OBJECTIVE: The aim of this study was to analyze the feasibility of wire/clip localization and sentinel lymph node biopsy (SLNB) for the axillary staging of these patients. METHODS: We conducted a prospective study in which lymph node staging was performed using wire localization of positive lymph nodes and an SLNB with dual tracer. All patients who presented no metastatic involvement of the sentinel lymph node (SLN) or clip/wire-marked lymph node were spared an axillary lymph node dissection (ALND). The multidisciplinary committee agreed on axillary treatment for patients with lymph node involvement. RESULTS: Forty-two patients met the inclusion criteria. We identified and extirpated the clip/wire-marked node in all patients (100%), with SLNB performed successfully in 95.3% of patients. The SLN and wire-marked node matched in 80% of patients; 73.8% of patients did not undergo ALND. DISCUSSION AND CONCLUSIONS: Several studies have evaluated the efficacy of various procedures for lymph node marking for women with prechemotherapy lymph node involvement. Most of the studies reported high identification rates (> 94.8%), with false negative rates of < 7%. Similarly, our study allows us to conclude that combined axillary marking (clip and SLNB) in patients with metastatic lymph node at diagnosis and NAC offers a high identification rate (100%) and a high correlation between the wire-marked lymph node and the SLN (80%). This procedure has enabled the suppression of ALND for a significant number of patients (73%).

SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer (2022).

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody-drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM.

Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).

INTRODUCTION: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain. MATERIAL AND METHODS: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients. RESULTS: A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment. CONCLUSION: The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.

[Proposal for a new multidisciplinary therapeutic strategy in the breast cancer patient with sentinel lymph node metastasis]. / Propuesta de una nueva estrategia terapéutica multidisciplinar en la mujer con cáncer de mama y afectación del ganglio centinela.

Sentinel lymph node (SLN) biopsy is the standard of practice for assessing axillary spread in clinically node-negative breast cancer patients. On the other hand, axillary lymph node dissection (ALND) is the ideal procedure for patients with SLN metastasis. Different studies over the last few years have suggested that some patients with positive SLN can be treated without ALND. This article presents a literature review carried out by our multidisciplinary group and its strategy for avoiding routine ALND in women with SLN metastases. In this new strategy ALND should not be performed on women with T1 tumours, with 1-2 positive SLN and undergoing breast conservative surgery. On the other hand, ALND would be indicated in those patients with three or more positive SLN, presence of extracapsular invasion, mastectomised women and triple negative subtype or HER2+ tumours that have not received biological treatment with antibodies.

[Venous thrombosis of atypical location in patients with cancer]. / Trombosis venosa de localización atípica en pacientes con cáncer.

Venous thromboembolism (VTE) is a complication that frequently occurs in patients with neoplastic diseases. Several models have therefore been developed to identify patient subgroups diagnosed with cancer who are at increased risk of developing VTE. The most common forms of thromboembolic episodes are deep vein thrombosis in the lower limbs and pulmonary thromboembolism. However, venous thrombosis is also diagnosed in atypical locations. There are few revisions of unusual cases of venous thrombosis. In most cases, VTE occurs in the upper limbs and in the presence of central venous catheters, pacemakers and defibrillators. We present the case of a patient diagnosed with breast cancer and treated with surgery, chemotherapy and radiation therapy who developed a thrombosis in the upper limbs (brachial and axillary).