The Use of Cyclin-Dependent Kinase 4/6 Inhibitors in Elderly Breast Cancer Patients: What Do We Know?

BACKGROUND: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. METHODS: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. RESULTS: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. CONCLUSION: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population.

Tripartite prehabilitation of patients with acute myeloid leukaemia and high-risk myelodysplastic syndromes during intensive chemotherapy before allogeneic haematopoietic stem cell transplantation (COHABILIT): protocol for an innovating prospective multicentre study.

OBJECTIVES: Acute myeloid leukaemia (AML) and high-risk myelodysplastic syndromes (MDS) are often treated with intensive chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT). The pretransplant treatment results in a general deterioration of the patient's health and quality of life. Furthermore, allo-HSCT can be responsible for significant toxicity with risks of graft-versus-host disease (GvHD). Developing strategies to prevent physical deconditioning, undernutrition and psychological distress could help maintain a satisfactory general state of health before transplantation and thus limit these deleterious effects. This protocol evaluates the feasibility and adherence to a personalised prehabilitation programme, which can be modulated and assisted by connected objects, provided from the diagnosis to the allo-HSCT. METHODS AND ANALYSIS: This multicentre interventional study will include 50 patients treated for AML or high-risk MDS with intensive chemotherapy and eligible for allo-HSCT. The intervention consists of a coached, supervised or self-directed physical activity programme, organised during the hospitalisation phases and periods at home. At the same time, patients will receive a weekly dietary follow-up. The whole intervention is controlled and modulated through the use of a dedicated application and connected objects allowing adaptation and individualisation. The rate of participation in the prescribed physical activity sessions will assess the feasibility of this study. In addition, the evolution of physical capacities (Short Physical Performance Battery, grip and quadriceps strengths), psychosocial parameters (Functional Assessment of Cancer Therapy - Leukaemia, Functional Assessment of Cancer Therapy - Fatigue, subjective well-being, Hospital Anxiety and Depression Scale, self-efficacy, Coach-Athlete Relationship Questionnaire, interviews) and clinical status (weight, lean body mass, survival rate, number of infections, days of hospitalisation, GvHD) will be evaluated. ETHICS AND DISSEMINATION: The study procedures have been approved by the National Ethics Committee (21.00223.000003). Consent is given in person by each participant. The information collected on the participants contains only a non-identifiable study identifier. The results of this protocol will be published in a scientific paper and communicated to the medical staff of the medical centre. TRIAL REGISTRATION NUMBER: NCT03595787.

Enhancing the referral process for surgical management of spinal metastases: insights from a 12-year, bi-institutional study of 533 patients.

Introduction: Delayed surgical management of spinal metastases (SMs) can have detrimental effects on patient survival and quality of life, leading to pain and potential neurological impairment. This study aimed to assess the impact of delayed referral for SMs on clinical outcomes by analyzing patients managed in emergency situations. Methods: We retrospectively reviewed the data of all patients admitted on either emergency or elective basis who underwent surgery for the treatment of neoplastic spine lesions at our two institutions (tertiary referral neurosurgical units) between January 2008 and December 2019. Results: We analyzed 210 elective (EGp) and 323 emergency patients (UGp); emergencies increased significantly over the 12-year period, with a Friday peak (39.3%) and frequent neurological impairment (61.6% vs. 20%). Among the UGp patients, 186 (7.5%) had a previously monitored primitive cancer, including 102 (31.6%) with known SMs. On admission, 71 of the 102 (69.9%) patients presented with neurological deficits. UGp patients were more likely to undergo a single decompression without fixation. Outcomes at the 3-month follow-up were significantly worse for UGp patients ([very] poor, 29.2 vs. 13.8%), and the median overall survival for UGp patients was statistically lower. Risk factors for patients with SM undergoing emergency management included short delay between onset of symptoms and first contact with a spine surgeon, and an initial motor deficit. Conclusion: Many patients with previously identified metastases, including those with neurological deficits, are urgently referred. Optimization is needed in the oncology pathway, and all stakeholders must be made aware of the factors contributing to the improvement in the clinical and radiological identification of potential complications affecting patient survival and quality of life.

Peripheral blood haploidentical hematopoietic cell transplantation for patients aged 70 years and over with acute myeloid leukemia or high-risk myelodysplastic syndrome.

Haploidentical stem cell transplantation (Haplo-SCT) using non-myeloablative conditioning regimen (NMAC) has extended the feasibility of allogeneic transplantation, notably in older patients. However, there is few data specifically focusing on patients aged 70 years and over with AML and MDS. Thus the benefit of transplantation in this population is still debated. Here we report our single center experience of peripheral blood Haplo-SCT with NMAC and post-transplantation cyclophosphamide in AML and MDS patients aged 70 years and over. We analyzed 50 patients (27 AML, 23 MDS) with a median age of 72 years (70-77), 12/50 (24%) with active disease at Haplo-SCT. Cumulative incidence of grade 3-4 acute and moderate or severe chronic GVHD were 6% and 25%, respectively. Non-relapse mortality (NRM) at day +100 was 0%. NRM, relapse, PFS and OS at 3 years were 16%, 18%, 66%, and 69%, respectively. Among patients who were disease free at 2 years post Haplo-SCT, 88% are living without immunosuppressive treatment. Peripheral blood Haplo-SCT is feasible in selected AML/MDS patients over 70 years, without any early NRM. It produces long-term disease control and survival. Thus, age by itself should not be considered as a formal barrier to Haplo-SCT.

[Very old patients in multidisciplinary team meeting in PACA: a one-year survey]. / Patients très âgés dans les RCP en région PACA : observation sur une année.

INTRODUCTION: In 2011, 11% of all cancers were diagnosed in people over 85 years old. With the current aging of the French population associated with health progress, we will be confronted more and more frequently with the treatment of very old patients, and this until the horizon 2050, when the population over 75 years old will represent approximately 15% of the total French population (compared to 9.1% in 2015). METHODS: To understand the management methods for patients over 85 years old with cancer, we carried out an observational study, based on data collected in the OncoPACA-Corse network, with the objective to describe the demographic data of very elderly patients, the characteristics of their pathology and to analyze the therapeutic strategies proposed by oncologists to patients in this population. RESULTS: One thousand three hundred and fifty five cases were analyzed. The mean age of the patients was 88.9 years with 3% of patients over 95 years old and only one was over 100 years old. 51.6% were women. Digestive tumors were the most represented (23.4%), followed by breast tumors (17.7%) and prostate tumors (10.5%), with a diagnosis made at a metastatic stage in 20% of cases. We note that treatment was offered for nearly 85% of patients with a wide range of options, exclusive palliative care was offered in 15% of cases; and whena treatment considered to be not very aggressive, such as hormone therapy, was offered, it seems to be preferred as monotherapy.

TRAINING-Ovary 01 (connecTed pRehabiliAtIoN pelvIc caNcer surGery): multicenter randomized study comparing neoadjuvant chemotherapy for patients managed for ovarian cancer with or without a connected pre-habilitation program.

BACKGROUND: Patients undergoing neoadjuvant chemotherapy before surgery for advanced ovarian cancer may have impaired functional capacity, nutritional status, and emotional well-being. PRIMARY OBJECTIVES: TRAINING-01 aims to determine if a connected pre-habilitation program during neoadjuvant chemotherapy for patients treated for an advanced ovarian cancer will improve physical capacity before major abdomino-pelvic surgery. STUDY HYPOTHESIS: A pre-habilitation program during neoadjuvant chemotherapy will bring a fitter patient to surgery and will decrease treatment morbidity and improve oncological outcomes. TRIAL DESIGN: This study is a prospective, multi-center, phase III study. The pre-habilitation program consists of providing multi-dimensional support during neoadjuvant chemotherapy using connected devices. The control group will receive usual care. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients will be women with International Federation of Gynecology and Obstetrics stage III-IV advanced ovarian cancer undergoing neoadjuvant chemotherapy. Patients must be able to perform a cardiopulmonary exercise test. PRIMARY ENDPOINTS: The primary endpoint will be the comparison of the variation in maximum oxygen uptake (VO2 max) between baseline and surgery in the pre-habilitation group and control groups. SAMPLE SIZE: 136 patients (68 per arm) will be recruited to demonstrate a medium standardized effect d=0.5 in the variations of VO2 max between baseline and surgery. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The duration of the study includes 24 months of recruitment and 5 years of follow up. We anticipate reporting primary endpoint results in 2024. TRIAL REGISTRATION: TRAINING-01-IPC 2018-039 (NCT04451369).

The "Friday peak" in surgical referrals for spinal metastases: lessons not learned. A retrospective analysis of 201 consecutive cases at a tertiary center.

BACKGROUND: Spinal cord compression and fracture are potential complications of spine metastasis (SM). Rapid management by an expert team can reduce these adverse developments. Delays in seeking therapeutic advices, which lead to the need for sub-optimal emergency procedures, were already demonstrated nearly 20 years ago. We aimed to analyze the current weak points of referrals for vertebral metastasis so as to improve the care pathways. METHODS: We retrospectively reviewed the data of all patients admitted on an emergency or elective basis who underwent palliative surgery for the treatment of neoplastic spine lesions in our institution (tertiary referral neurosurgical unit) between January 2009 and December 2016. RESULTS: This retrospective study included 201 patients, 121 men and 80 women (mean age 65.1 years ± 10.9). Cancer was known for 59.7% of cases. Patients were neurologically asymptomatic in 52.7% of cases (Frankel E), and 123 (60.7%) were hospitalized for emergency reasons, including 51 (41.5% of emergencies) on a Friday (p < 0.0001). A significant increase in emergencies occurred over the studied period (p = 0.0027). The "emergency" group had significantly unfavorable results in terms of neurological status (p < 0.001), the occurrence of complications (p = 0.04), the duration of hospitalization (p = 0.02), and the clinical evolution (p = 0.04). Among 123 patients hospitalized for emergency reasons, 65 (52.8%) had known cancers, of which 33 had an identified SM, including 22 with neurological deficits (Frankel A-D), without prior surgical assessment (17.8% of emergencies). CONCLUSION: Too many patients with previously identified metastases are referred for emergency reasons, including with a neurological deficit. Optimizing upstream pathways and referrals is imperative for improving the management of these patients. Involving a spine surgeon at the slightest symptom or an abnormal image is critical for defining the best treatment upstream. The use of telemedicine and the development of dedicated tumor boards are ways of improving this involvement.

Enhanced recovery after surgery program in older patients undergoing gynaecologic oncological surgery is feasible and safe.

BACKGROUND: Enhanced Recovery After Surgery Programs (ERP) include multimodal approaches of perioperative patient's clinical pathways designed to achieve early recovery after surgery and a decreased length of hospital stay (LOS). By allowing patients to return rapidly to their everyday surroundings, older patients are those who could take the greatest benefit from ERP. This is the first study to date to assess feasibility and safety of ERP on older patients undergoing gynaecologic oncological surgery. METHODS: Data were prospectively collected between December 2015 and September 2017 at the Institut Paoli-Calmettes, a French comprehensive cancer centre. All the patients included in the study were referred for hysterectomy and/or pelvic or para-aortic lymphadenectomy for gynaecological cancer. The primary objective was to achieve similar LOS in patients ≥70 years old compared to younger patients without increasing the proportion of complications and readmission rates. A binary (LOS < or ≥ 2 days) logistic regression was built, including age, Charlson score, BMI, ASA score, oncological indication, surgical procedures and surgical approaches. G8 score was estimated for all the ≥70 years old patients. RESULTS: Of a total of 329 patients, 75 were ≥70 years old and 254 were <70. Except a disparity in oncological indications with a higher proportion of endometrial cancer in the ≥70 years old group (56% vs. 27%; p < 0.01), there were no differences in patient's characteristics and surgical procedures. Age ≥ 70 years was associated with a longer LOS (means, 3.88 vs. 3.11 days; p = 0.024) only in univariate analysis. Considering the logistic regression, age was no longer associated with LOS. Total hysterectomy with pelvic lymphadenectomy and ASA score ≥ 3 were independently associated with longer LOS while mini-invasive techniques were associated with a shorter LOS. Morbidities and readmissions occurred respectively in 23% and 8% of the total population without any difference between the two groups. In the ≥70 years old population, G8 score was not predictive of LOS, morbidities or readmissions. CONCLUSION: Although it is already widely accepted that ERP improves early recovery, our study shows that ERP for patients over 70 years of age undergoing gynaecologic oncological surgery is as safe and feasible as on younger patients.

Nivolumab in routine practice for older patients with advanced or metastatic non-small cell lung cancer.

BACKGROUND: Nivolumab is approved worldwide as second-line treatment for metastatic non-small cell lung cancer (NSCLC). Despite the fact that most of these cancers are being diagnosed in the older patients, few of the patients were included in pivotal trials. We aimed to describe efficacy and safety in a "real-world" older population. PATIENTS AND METHODS: We retrospectively collected data from older patients (≥70 years old) with advanced or metastatic NSCLC treated with Nivolumab in our institution. We analyzed safety (CTCAE v4.0 criteria), efficacy (clinical benefit rate, progression-free survival, and overall survival), and correlated these features to geriatric parameters and PD-L1 expression. Along with this cohort, we assessed safety at a national level by retrieving all cases of Nivolumab (prescribed for NSCLC) induced adverse events analyzed by the French pharmacovigilance network during the inclusion period. RESULTS: From July 2015 to September 2016, 30 patients were enrolled with a median age of 75.2. Clinical benefit rate was 30.6%. Median progression-free survival and overall survival were 3.3 and 7.1 months, respectively. Fifteen patients (50%) presented an immune-related adverse event (IrAE) of any grade, including four high grade IrAEs. Two hundred and eighty IrAEs had been notified to the French pharmacovigilance network including 91 (35.2%) concerning older patients. Frequency and pattern of IrAEs were similar for older patients and younger subjects. CONCLUSIONS: Even though frequency and patterns of IrAEs are different from pivotal studies, these results don't seem specific to older patients. Further prospective investigations are needed to better characterize and predict the impact of Nivolumab on older patients with NSCLC.

Malnutrition in Patients With Cancer: Comparison of Perceptions by Patients, Relatives, and Physicians-Results of the NutriCancer2012 Study.

BACKGROUND: Malnutrition is a critical predictor of toxicity and outcome in patients with cancer and may be perceived differently by patients, relatives, and physicians. AIMS: To assess the prevalence of malnutrition in oncology departments and to compare it with the perceptions of nutrition status by patients themselves, their closest relatives, and attending physicians. MATERIALS AND METHODS: A 1-day multicentric cross-sectional survey on the prevalence of malnutrition was conducted in different oncology departments using patient-, relative-, and physician-specific questionnaires. Malnutrition was defined by a weight loss ≥5% within 1 month or ≥10% within 6 months, a body mass index ≤18.5 kg/m2 in patients aged <70 years or ≤21 kg/m2 in patients aged ≥70 years, and/or albuminemia <35 g/L. Questionnaires for assessing medical condition, knowledge of nutrition status, and perceptions of the impact of malnutrition on daily life were distributed to consenting patients, attending physicians, and closest relatives. RESULTS: A total of 2197 patients were included, and 2071 and 976 questionnaires were collected from patients and relatives, respectively. Prevalence of malnutrition was 39%. Physicians overestimated malnutrition (44%), whereas patients and relatives underestimated it (22% and 23%, respectively, P < .001). Conversely, malnutrition-associated symptoms were underestimated by physicians compared with patients and relatives. CONCLUSION: We found a prevalence of malnutrition of 39%: it was underestimated by patients and relatives and overestimated by physicians.