Consore: A Powerful Federated Data Mining Tool Driving a French Research Network to Accelerate Cancer Research.

BACKGROUND: Real-world data (RWD) related to the health status and care of cancer patients reflect the ongoing medical practice, and their analysis yields essential real-world evidence. Advanced information technologies are vital for their collection, qualification, and reuse in research projects. METHODS: UNICANCER, the French federation of comprehensive cancer centres, has innovated a unique research network: Consore. This potent federated tool enables the analysis of data from millions of cancer patients across eleven French hospitals. RESULTS: Currently operational within eleven French cancer centres, Consore employs natural language processing to structure the therapeutic management data of approximately 1.3 million cancer patients. These data originate from their electronic medical records, encompassing about 65 million medical records. Thanks to the structured data, which are harmonized within a common data model, and its federated search tool, Consore can create patient cohorts based on patient or tumor characteristics, and treatment modalities. This ability to derive larger cohorts is particularly attractive when studying rare cancers. CONCLUSIONS: Consore serves as a tremendous data mining instrument that propels French cancer centres into the big data era. With its federated technical architecture and unique shared data model, Consore facilitates compliance with regulations and acceleration of cancer research projects.

Early morning immune checkpoint blockade and overall survival of patients with metastatic cancer: An In-depth chronotherapeutic study.

INTRODUCTION: Recent retrospective studies suggest potential large patient's benefit through proper timing of immune checkpoint blockers (ICB). The association between ICB treatment timing and patient survival, neoplastic response and toxicities was investigated, together with interactions with performance status (PS) and sex. METHODS: A cohort of patients with metastatic or locally advanced solid tumors, who received pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab, alone or with concomitant chemotherapy, between November 2015 and March 2021, at the Centre Leon Bérard (France), was retrospectively studied. RESULTS: 361 patients were investigated (80% non-small cell lung cancer patients, mean [SD] age: 63 [11] years, 39% of women, 83% PS0-1 at first infusion, 19% received concomitant chemotherapy). ICB were administered from 07:25 to 17:21 and optimal morning/afternoon cut-off was 11:37. Morning infusions were associated with increased OS as compared to afternoon (median 30.3 vs 15.9 months, p = 0.0024; HR 1.56 [1.17-2.1], p = 0.003). A strong PS-timing interaction was found (PS0-1 patients, HR=1.53 [1.10-2.12], p = 0.011; PS2-3 patients, HR=0.50 [0.25-0.97], p = 0.042). Morning PS0-1 patients displayed increased OS (median 36.7 vs 21.3 months, p = 0.023), partial/complete response rate (58% vs 41%, p = 0.027), and grade1-3 toxicities (49% vs 34%, p = 0.028). Mortality risk ratio between infusions at worst time-of-day, estimated at 13:36 [12:48-14:23], and in early morning was equal to 4.8 ([2.3-10.1], p = 0.008). Timing differences in toxicities resulted significant only in female patients (women vs men: p < 0.001 vs 0.4). CONCLUSIONS: Early morning ICB infusion was associated with increased OS, response, and toxicities in patients with PS0-1 as compared to later infusions within the day. Prospective randomized trials are needed to confirm this retrospective study.

From data strategy to implementation to advance cancer research and cancer care: A French comprehensive cancer center experience.

In a comprehensive cancer center, effective data strategies are essential to evaluate practices, and outcome, understanding the disease and prognostic factors, identifying disparities in cancer care, and overall developing better treatments. To achieve these goals, the Center Léon Bérard (CLB) considers various data collection strategies, including electronic medical records (EMRs), clinical trial data, and research projects. Advanced data analysis techniques like natural language processing (NLP) can be used to extract and categorize information from these sources to provide a more complete description of patient data. Data sharing is also crucial for collaboration across comprehensive cancer centers, but it must be done securely and in compliance with regulations like GDPR. To ensure data is shared appropriately, CLB should develop clear data sharing policies and share data in a controlled, standardized format like OSIRIS RWD, OMOP and FHIR. The UNICANCER initiative has launched the CONSORE project to support the development of a structured and standardized repository of patient data to improve cancer research and patient outcomes. Real-world data (RWD) studies are vital in cancer research as they provide a comprehensive and accurate picture of patient outcomes and treatment patterns. By incorporating RWD into data collection, analysis, and sharing strategies, comprehensive cancer centers can take a more comprehensive and patient-centered approach to cancer research. In conclusion, comprehensive cancer centers must take an integrated approach to data collection, analysis, and sharing to enhance their understanding of cancer and improve patient outcomes. Leveraging advanced data analytics techniques and developing effective data sharing policies can help cancer centers effectively harness the power of data to drive progress in cancer research.

A qualitative study of teleconsultation practices among French oncologists in a post-COVID-19 period.

Background: The Covid-19 pandemic has prompted healthcare professionals to adapt and implement new tools to ensure continuity of patient care. Teleconsultation became the only option for some practitioners who had never used it previously and boosted its use for others who already used it. Several studies have reviewed the use of teleconsultation in oncology during the epidemic, but few have addressed its continued use and how practitioners view it in a post-epidemic period. The aim of this survey was to conduct a qualitative exploration of how oncologists use teleconsultation in their daily practice in a post-COVID 19 period. Materials and Methods: For this qualitative study, semi-structured interviews were conducted with oncologists in France who utilized teleconsultation in the field of oncology during the COVID-19 period. The interview guide included questions on the interests and limitations of using teleconsultation in oncology, on reluctance to use it among oncologists, and invited participants to formulate proposals for more optimal use. Results: Fourteen oncologists participated in the survey. Currently, 12% of the consultations of the surveyed practitioners are conducted via teleconsultation. Seven themes were identified in the analysis of the interviews: (a) The oncologist and teleconsultation; (b) Clinical motivations for using teleconsultation; (c) Comparison between teleconsultation and in-person consultation; (d) Advantages and disadvantages of teleconsultation; (e) Technical modalities of teleconsultation; (f) Role of Covid and confinement in the use of teleconsultation; (h) Epistemic judgments about teleconsultation. Optimal teleconsultation occurs when seamlessly incorporated into patient care, offering reduced patient inconvenience, and providing economic and environmental benefits. Although there's a lack of unified agreement in research literature regarding time efficiency, teleconsultation facilitates more customized patient monitoring and addresses the challenge of "medical deserts" nationally. Considering patient preferences is crucial when contemplating the use of teleconsultation. Predominantly, technical issues stand as the principal barriers to teleconsultation implementation. Conclusion: Even after the end of the health crisis, teleconsultation is still used in clinical practice. Recommendations for effective use are suggested.

Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial.

PURPOSE: Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy. PATIENTS AND METHODS: ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1-positive populations (alpha .025 for each population). RESULTS: Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1-positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1-positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively). CONCLUSION: ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1-positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.

Adjuvant therapeutic strategy decision support for an elderly population with localized breast cancer: A monocentric cohort retrospective study.

Guidelines for the management of elderly patients with early breast cancer are scarce. Additional adjuvant systemic treatment to surgery for early breast cancer in elderly populations is challenged by increasing comorbidities with age. In non-metastatic settings, treatment decisions are often made under considerable uncertainty; this commonly leads to undertreatment and, consequently, poorer outcomes. This study aimed to develop a decision support tool that can help to identify candidate adjuvant post-surgery treatment schemes for elderly breast cancer patients based on tumor and patient characteristics. Our approach was to generate predictions of patient outcomes for different courses of action; these predictions can, in turn, be used to inform clinical decisions for new patients. We used a cohort of elderly patients (≥ 70 years) who underwent surgery with curative intent for early breast cancer to train the models. We tested seven classification algorithms using 5-fold cross-validation, with 80% of the data being randomly selected for training and the remaining 20% for testing. We assessed model performance using accuracy, precision, recall, F1-score, and AUC score. We used an autoencoder to perform dimensionality reduction prior to classification. We observed consistently better performance using logistic regression and linear discriminant analysis models when compared to the other models we tested. Classification performance generally improved when an autoencoder was used, except for when we predicted the need for adjuvant treatment. We obtained overall best results using a logistic regression model without autoencoding to predict the need for adjuvant treatment (F1-score = 0.869).

A Digital Solution for an Advanced Breast Tumor Board: Pilot Application Cocreation and Implementation Study.

BACKGROUND: Cancer treatment is constantly evolving toward a more personalized approach based on clinical features, imaging, and genomic pathology information. To ensure the best care for patients, multidisciplinary teams (MDTs) meet regularly to review cases. Notwithstanding, the conduction of MDT meetings is challenged by medical time restrictions, the unavailability of critical MDT members, and the additional administrative work required. These issues may result in members missing information during MDT meetings and postponed treatment. To explore and facilitate improved approaches for MDT meetings in France, using advanced breast cancers (ABCs) as a model, Centre Léon Bérard (CLB) and ROCHE Diagnostics cocreated an MDT application prototype based on structured data. OBJECTIVE: In this paper, we want to describe how an application prototype was implemented for ABC MDT meetings at CLB to support clinical decisions. METHODS: Prior to the initiation of cocreation activities, an organizational audit of ABC MDT meetings identified the following four key phases for the MDT: the instigation, preparation, execution, and follow-up phases. For each phase, challenges and opportunities were identified that informed the new cocreation activities. The MDT application prototype became software that integrated structured data from medical files for the visualization of the neoplastic history of a patient. The digital solution was assessed via a before-and-after audit and a survey questionnaire that was administered to health care professionals involved in the MDT. RESULTS: The ABC MDT meeting audit was carried out during 3 MDT meetings, including 70 discussions of clinical cases before and 58 such discussions after the implementation of the MDT application prototype. We identified 33 pain points related to the preparation, execution, and follow-up phases. No issues were identified related to the instigation phase. Difficulties were grouped as follows: process challenges (n=18), technological limitations (n=9), and the lack of available resources (n=6). The preparation of MDT meetings was the phase in which the most issues (n=16) were seen. A repeat audit, which was undertaken after the implementation of the MDT application, demonstrated that (1) the discussion times per case remained comparable (2 min and 22 s vs 2 min and 14 s), (2) the capture of MDT decisions improved (all cases included a therapeutic proposal), (3) there was no postponement of treatment decisions, and (4) the mean confidence of medical oncologists in decision-making increased. CONCLUSIONS: The introduction of the MDT application prototype at CLB to support the ABC MDT seemed to improve the quality of and confidence in clinical decisions. The integration of an MDT application with the local electronic medical record and the utilization of structured data conforming to international terminologies could enable a national network of MDTs to support sustained improvements to patient care.

Pembrolizumab in Lymphopenic Metastatic Breast Cancer Patients Treated with Metronomic Cyclophosphamide: A Clinical and Translational Prospective Study.

Purpose: Metastatic endocrine-resistant breast cancer (MBC) is a disease with poor prognosis and few treatment options. Low lymphocyte count is associated with limited overall survival. In a prospective cohort of lymphopenic patients with HER-2 negative MBC, we assessed the clinical and biological impact of pembrolizumab combined with metronomic cyclophosphamide. Experimental Design: This multicenter Phase II study evaluated the safety and clinical activity of pembrolizumab (intravenous (IV), 200mg, every 3 weeks) combined with metronomic cyclophosphamide (50mg/day, per os) in lymphopenic adult patients with HER2-negative MBC previously treated by at least one line of chemotherapy in this setting according to a Simon's minimax two-stage design. Blood and tumor samples were collected to assess the impact of the combined treatment on circulating immune cells and the tumor immune microenvironment through multiparametric flow cytometry and multiplex immunofluorescence analyses. Primary endpoint was the clinical benefit rate at 6 months of treatment (CBR-6M). Secondary endpoints were objective response rate (ORR), duration of response, progression free survival (PFS), and overall survival (OS). Results: Two out of the twenty treated patients presented clinical benefit (one Tumor Mutational Burden (TMB)-high patient with complete response (CR) and one patient with objective response (OR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) associated with a strong increase of cytokine-producing and proliferating CD4+ T cells and higher CD8+ T cells to macrophage ratios in the tumor. This impact on CD4+ and CD8+ T cell polyfunctionality was still observed more than one year for the patient with CR. A decreased in their absolute number of CD4+ and CD8+ memory T cells was observed in other patients. Conclusion: Pembrolizumab combined with metronomic cyclophosphamide was well tolerated, and displayed limited anti-tumoral activity in lymphopenic MBC. Correlative translational data of our trial advocates for additional studies with other chemotherapy combinations.

Association of chemotherapy and comorbidities with overall survival in elderly patients with early breast cancer: a French population-based propensity score-matched analysis.

BACKGROUND: Additional systemic treatment for early breast cancer in elderly is challenged by increasing comorbidities with age. We aimed to examine the effect of additional chemotherapy on overall survival in patients aged 70 years or older and the impact of comorbidities on chemotherapy benefit. METHODS: This retrospective monocentric cohort study includes data from all patients aged 70 years and older who underwent surgery for an early breast cancer from 1997 to 2016. A propensity score analysis allowed adjustment for chemotherapy prescription preferences based on tumour characteristics. RESULTS: Of 15,599 patients who had surgery for an early breast cancer, 1743 (11.2%) over 70 years old were included, of whom 269 (15.4%) had received additional chemotherapy. Median follow-up was 5.3 years. Multivariate analyses on the propensity-score weighted cohort (n = 1 354) identified improved overall survival in patients with chemotherapy versus without (HR 0.54, 95% CI 0.31-0.92). Chronic obstructive pulmonary disease (HR, 2.16, 95% CI 1.40-3.34) and polypharmacy (HR 1.40, 95%CI 1.07-1.84) were associated with worse overall survival. No statistically significant interactions were identified between these comorbidities and chemotherapy prescription. CONCLUSION: Additional chemotherapy in elderly with early breast cancer is feasible and associated with overall survival benefit, supporting the importance of chemotherapy considerations in this population, and of avoiding undertreatment based on chronological age considerations alone.

Federated learning for predicting histological response to neoadjuvant chemotherapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a rare cancer, characterized by high metastatic potential and poor prognosis, and has limited treatment options. The current standard of care in nonmetastatic settings is neoadjuvant chemotherapy (NACT), but treatment efficacy varies substantially across patients. This heterogeneity is still poorly understood, partly due to the paucity of curated TNBC data. Here we investigate the use of machine learning (ML) leveraging whole-slide images and clinical information to predict, at diagnosis, the histological response to NACT for early TNBC women patients. To overcome the biases of small-scale studies while respecting data privacy, we conducted a multicentric TNBC study using federated learning, in which patient data remain secured behind hospitals' firewalls. We show that local ML models relying on whole-slide images can predict response to NACT but that collaborative training of ML models further improves performance, on par with the best current approaches in which ML models are trained using time-consuming expert annotations. Our ML model is interpretable and is sensitive to specific histological patterns. This proof of concept study, in which federated learning is applied to real-world datasets, paves the way for future biomarker discovery using unprecedentedly large datasets.

CHEOPS trial: a GINECO group randomized phase II assessing addition of a non-steroidal aromatase inhibitor to oral vinorelbine in pre-treated metastatic breast cancer patients.

BACKGROUND: The objective of the CHEOPS trial was to assess the benefit of adding aromatase inhibitor (AI) to metronomic chemotherapy, oral vinorelbine, 50 mg, three times a week for pre-treated, HR + /HER2- metastatic breast cancer patients. METHODS: In this multicentric phase II study, patients had to have progressed on AI and one or two lines of chemotherapy. They were randomized between oral vinorelbine (Arm A) and oral vinorelbine with non-steroidal AI (Arm B). RESULTS: 121 patients were included, 61 patients in Arm A and 60 patients in Arm B. The median age was 68 years. 109 patients had visceral metastases. They all had previously received an AI. The study had been prematurely stopped following the third death due to febrile neutropenia. Median PFS trend was found to be different with 2.3 months and 3.7 months in Arm A and Arm B, respectively (HR 0.73, 95%CI 0.50-1.06, p value = 0.0929). No statistical difference was shown in OS and better tumor response. 56 serious adverse events corresponding to 25 patients (21%) were reported (respectively, 12 (20%) versus 13 (22%) for arms A and B) (NS). CONCLUSION: The addition of AI to oral vinorelbine over oral vinorelbine alone in aromatase inhibitor-resistant metastatic breast cancer was associated with a non-significant improvement of PFS. Several unexpected serious adverse events were reported. Metronomic oral vinorelbine schedule, at 50 mg three times a week, requires close biological monitoring. The question of hormonal treatment and chemotherapy combination remains open.

Ribosome biogenesis-based predictive biomarkers in endocrine therapy (Anastrozole) combined with mTOR inhibitor (Vistusertib) in endometrial cancer: translational study from the VICTORIA trial in collaboration with the GINECO group.

Resistance of advanced hormone-dependent endometrial carcinoma to endocrine therapy remains a worldwide clinical issue. We recently reported that the combination of Vistusertib (V, mTOR inhibitor) and Anastrozole (A, aromatase inhibitor) improves the progression-free rate compared to Anastrozole alone. However, a better patient selection based on biomarkers would improve patient outcome. We evaluate for the first time the usage of ribosome biogenesis (RiBi) factors as a source of innovative markers. Using 47 FFPE tumours (A n = 18; V + A n = 29), 32 blood samples (A n = 13; V + A n = 19) and 30 samples of total RNAs (A n = 12; V + A n = 18) from the VICTORIA clinical trial, we observed an association between RiBi-associated markers and drug activity or prediction of treatment response. NOP10 and NHP2 mRNA levels were significantly higher in non-responders compared to responders in the Vistusertib + Anastrozole arm (P = 0.0194 and P = 0.0002 respectively; i.e. 8 weeks progression-free survival as endpoint). This study provides RiBi-based markers relevant for a better selection of patients with advanced endometrial carcinoma by predicting the response of endocrine therapy combined with mTOR inhibitor.

Alterations in Homologous Recombination-Related Genes and Distinct Platinum Response in Metastatic Triple-Negative Breast Cancers: A Subgroup Analysis of the ProfiLER-01 Trial.

BACKGROUND: a specific subset of metastatic triple-negative breast cancers (mTNBC) is characterized by homologous recombination deficiency (HRD), leading to enhanced sensitivity to platinum-based chemotherapy. Apart from mutations in BRCA1/2 genes, the evaluation of other HRD-related alterations has been limited to date. As such, we analyzed data from mTNBC patients enrolled in the ProfiLER-01 study to determine the prevalence of alterations in homologous recombination-related (HRR) genes and their association with platinum sensitivity. METHODS: next-generation sequencing and promoter methylation of BRCA1 and RAD51C were performed on tumors from patients with mTNBC, using a panel of 19 HRR genes. Tumors were separated into three groups based on their molecular status: mutations in BRCA1/2, mutations in other HRR genes (BRCA1/2 excluded) or BRCA1/RAD51C promoter methylation and the absence of molecular alterations in HRR genes (groups A, B and C, respectively). Sensitivity to platinum-based chemotherapy was evaluated through the radiological response. RESULTS: mutations in BRCA1/2 were detected in seven (13.5%) patients, while alterations in other HRR genes or hypermethylation in BRCA1 or RAD51C were reported in 16 (30.7%) patients; furthermore, no alteration was found in the majority of patients (n = 29; 55.8%). Among 27 patients who received platinum-based chemotherapy, the disease control rate was 80%, 55% and 18% (groups A, B and C, respectively; p = 0.049). Regarding group B, patients with disease control exhibited mutations in FANCL, FANCA and the RAD51D genes or RAD51C methylation; Conclusion: mutations in HRR genes and epimutations in RAD51C were associated with disease control through platinum-based chemotherapy. As such, apart from well-characterized alterations in BRCA1/2, a more comprehensive evaluation of HRD should be considered in order to enlarge the selection of patients with mTNBC that could benefit from platinum-based chemotherapy.

The Ambulatory Medical Assistance (AMA) programme during active-phase treatment in patients with haematological malignancies: A cost-effectiveness analysis.

CONTEXT: The need for patient navigator is growing, and there is a lack of cost evaluation, especially during survivorship. OBJECTIVE: The objective of this study is to evaluate the cost-effectiveness of an Ambulatory Medical Assistance (AMA) programme in patients with haematological malignancies (HM). DESIGN: A cost-effectiveness analysis of the AMA programme was performed compared to a simulated control arm. SETTING: An interventional, single-arm and prospective study was conducted in a French reference haematology-oncology centre between 2016 and 2020. PARTICIPANTS: Adult patients were enrolled with histologically documented malignant haematology, during their active therapy phase, and treated either by intravenous chemotherapy or oral therapy. METHODS: An extrapolation of the effectiveness was derived from a similar nurse monitoring programme (CAPRI study). Cost effectiveness of the programme was evaluated through adverse events of Grade 3 or 4 avoided in different populations. RESULTS: Included patient (n = 797) from the AMA programme were followed during 125 days (IQR: 0-181), and adverse events (Grade 3/4) were observed in 10.1% of patients versus 13.4% in the simulated control arm. The overall cost of AE avoided was estimated to €81,113, leading to an ICER of €864. CONCLUSION: The AMA programme was shown to be cost-effective compared to a simulated control arm with no intervention.

[Survey on the practice of medical teleconsultation in oncology in Auvergne Rhône Alpes]. / Enquête sur la pratique de la téléconsultation médicale en oncologie en Auvergne Rhône Alpes.

RATIONAL: Teleconsultation (TLC) practice, which suddenly arrived in the cancer patients care, has experienced an undeniable quantitative boom given the health context. A quantitative and qualitative assessment of this practice now seems necessary. This study aims to describe the use of TLC by oncologists in the Auvergne-Rhône-Alpes region during the pandemic in order to assess its advantages and limits, and to estimate the barriers encountered and the possible levers for its promotion in oncology. METHOD: The use of TLC in daily medical practice was evaluated using a descriptive observational survey from October to December 2021. Health's professionals were invited to answer an online survey composed of around thirty questions. RESULTS: Of the 200 oncologists contacted, 72 took part in the survey. Among them, 64 have already made at least one TLC. TLCs represented 25 % of consultations during the confinement period. New cancer patients, the fact of not seeing the patient physically and the absence of the possibility of carrying out a physical examination are the 3 main obstacles to TLC. The mastery of computer tools is one of the main levers. All cancer patients appear eligible for TLC ; the professionals surveyed prefer this solution for certain socio-demographic and medical characteristics of the patients (the fact of living far from the cancer centre, of having a stable clinical situation, of being under surveillance or being treated with oral anti-cancer drugs…). Despite a median level of satisfaction of 63 % estimated by doctors, less than 10 % of medical consultations are currently kept in TLC. CONCLUSION: TLC is now an integrated practice in oncology but seems more relevant for a specific patient profile and clinical situation. In addition, technical and training constraints still limit its use in clinical practice today.

Safety and Efficacy of the mTOR Inhibitor, Vistusertib, Combined With Anastrozole in Patients With Hormone Receptor-Positive Recurrent or Metastatic Endometrial Cancer: The VICTORIA Multicenter, Open-label, Phase 1/2 Randomized Clinical Trial.

Importance: Endometrial cancer is often hormone-dependent and treated with aromatase inhibitors. The PI3K-AKT-mTOR pathway deregulation observed in endometrial cancer drives hormonal resistance, thus supporting the rationale of combining mTOR inhibitor with endocrine therapy. Objective: To evaluate the safety and efficacy of vistusertib in combination with anastrozole in the treatment of women with hormone receptor-positive recurrent or metastatic endometrial cancer. Design, Settings, and Participants: The VICTORIA study was a multicenter, open-label, randomized clinical trial that accrued 75 patients with hormone receptor-positive recurrent or metastatic endometrial cancer from 12 cancer centers in France in April 2016 to October 2019. After a safety run-in period, a Simon 2-stage design was used. Data analyses were performed from December 11, 2020, to March 11, 2021. Interventions: Patients were randomized in a 2:1 ratio to oral vistusertib (125 mg twice daily 2 days per week) and oral anastrozole (1 mg daily) in the combination vistusertib with anastrozole arm (V+A arm) or oral anastrozole alone (A arm). Main Outcomes and Measures: The primary end point was serious adverse events for the safety run-in period and progression-free rate at 8 weeks (8wk-PFR)-assessed with a blinded independent central review in phase 2. The secondary end points were objective response rate, duration of response, progression-free survival (PFS), overall survival, and incidence of adverse events. Results: Of the 75 patients who were randomized, 73 (median [range] age, 69.5 [37-88] y; all female) were treated: V+A arm, 49 patients; A arm, 24 patients. In the V+A arm, the 8wk-PFR was 67.3% (unilateral 95% CI, 54.7%) and in the A arm, 39.1% (unilateral 95% CI, 22.2%). No significant serious adverse events were reported during the safety run-in period (n = 6 in V+A arm). The overall response rate was 24.5% (95% CI, 13.3%-38.9%) in the V+A arm vs 17.4% (95% CI, 5.0%-38.8%) in the A arm. With a median follow-up of 27.7 months, median PFS was 5.2 (95% CI, 3.4-8.9) in the V+A arm and 1.9 (95% CI, 1.6-8.9) months in the A arm. Fatigue, lymphopenia, hyperglycemia, and diarrhea were the most common (grade ≥2) adverse events associated with vistusertib. Conclusions and Relevance: This multicenter, open-label, phase 1/2 randomized clinical trial demonstrated that adding vistusertib to anastrozole improved 8wk-PFR, overall response rate, and PFS for patients with endometrial cancer and had manageable adverse events. Identification of molecular subgroups would allow for more precise selection of patients who may be most likely to experience favorable outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02730923.

Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer.

BACKGROUND: Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes. METHODS: Secondary end-points of NEOPAL included progression-free survival (PFS) and invasive-disease free survival (iDFS) in the intent-to-treat population. Exploratory end-points were overall survival (OS) and breast cancer specific survival (BCSS) in the intent-to-treat population, as well as iDFS, OS and BCSS according to the administration of chemotherapy. RESULTS: Hundred and six patients were randomised. Pathological complete response rates were 3.8% and 5.9%. Twenty-three of the 53 patients in the letrozole-palbociclib arm received postoperative adjuvant chemotherapy. At a median follow-up of 40.4 months [0-56.6], 11 progressions have been observed, of which three were in the letrozole-palbociclib and 8 in the control arm. PFS (HR = 1.01; [95%CI 0.36-2.90], p = 0.98) and iDFS (HR = 0.83; [95%CI 0.31-2.23], p = 0.71) did not differ between both arms. The 40 months PFS rate was 86.7% [95%CI 78.0-96.4] and 89.9% [95%CI 81.8-98.7] in letrozole-palbociclib and control arms, respectively. Outcomes of patients who did not receive chemotherapy were not statistically different from those who received it. CONCLUSIONS: NEOPAL suggests that a neoadjuvant letrozole-palbociclib strategy may allow sparing chemotherapy in some patients with luminal breast cancer while allowing good long-term outcomes. Larger confirmatory studies are needed.

Survival and risk of COVID-19 after SARS-COV-2 vaccination in a series of 2391 cancer patients.

BACKGROUND: Patients with cancer are at high risk of severe or lethal COVID-19. The impact of SARS-COV-2 vaccination on the risk of developing COVID-19 was investigated in an exhaustive series of patients from a comprehensive cancer center. METHODS: This is a study of the exhaustive population of 2391 cancer patients who were prescribed SARS-COV-2 vaccination until 09/21. Patient characteristics, documented SARS-COV-2 infection with RT-PCR, and survival were collected. The primary endpoint was the rate of COVID-19 after vaccination. Secondary endpoints included risk factors to develop COVID-19 after vaccination, with a comparison with the cohort of vaccinated health care workers (HCW), and risk factors for death. RESULTS: From January to September 2021, among 2391 patients with cancer under active treatment in whom a SARS-COV-2 vaccine was prescribed, 659 (28%), 1498 (63%) and 139 (6%) received 1, 2, and 3 doses, respectively. Ninety five patients received a single dose of vaccine after a previous COVID-19. Two thousand two hundred eighty five health care workers (HCW) received one (N = 17, 0.7%), 2-3 (N = 2026, 88.7%) vaccine doses and one dose after COVID-19 (N = 242, 10.6%). With a median follow-up of 142 and 199 days for patients and HCW, respectively. Thirty nine (1.6%) patients and 35 (1.5%) HCW developed COVID-19 after vaccination. Six of 39 cancer patients and no HCW died because ofCOVID-19 within 50 days after diagnosis. Independent risk factors for COVID-19 in vaccinated patients were age, single dose of vaccine without previous COVID-19 and anti-CD20 treatment in the last three months. Independent risk factors for death included metastatic disease, gender, cancer type, but also documented COVID-19 before vaccination. CONCLUSIONS: Patients receiving two or more doses of COVID-19 vaccine have reduced risk of COVID-19. The risk of death of vaccinated cancer patients presenting COVID-19 remains high. COVID-19 before vaccination is associated with an increased overall risk of death.

Impact of Limited E-Health Literacy on the Overall Survival of Patients With Cancer.

PURPOSE: Digitalization of the health care system is transforming cancer patient care. Although many studies have investigated the determinants of a limited digital health literacy, the association between frailty factors and overall survival (OS) of these patients has never been assessed. METHODS: A retrospective noninterventional study included 15,244 adult patients with cancer diagnosed between January 1, 2015, and December 31, 2017, and treated at the Centre Léon Bérard. Limited e-health literacy was defined as the absence of an e-mail address in the electronic patient record. An Inverse Probability of Treatment-Weighted Kaplan-Meier estimate and a multivariate Cox proportional hazards model including interaction terms were used to adjust for confounding on measured covariates. RESULTS: In total, 15,244 adults with cancer were included: 55% women, with a median age of 62 years (19-103), and 35.5% had a metastatic disease. More than half (n = 8,771, 57.5%) had entered their e-mail address in their electronic patient record, and 4,020 (26.4%) opened their own patient portal. The median follow-up was 3.6 years (range: 0-6.8). Inverse Probability of Treatment-weighted Kaplan-Meier estimates showed a significantly better OS for patients with an e-mail address (P < .001). In multivariate analysis integrating interaction terms, male gender (hazard ratio [HR] = 1.27; 95% CI, 1.15 to 1.41; P < .001), older age (HR = 1.02; 95% CI, 1.02 to 1.03; P < .001), de novo metastatic setting (HR = 2.63; 95% CI, 2.47 to 2.79; P < .001), and no e-mail address (HR = 1.63; 95% CI, 1.33 to 2.00; P < .001) were significantly associated with worse OS. CONCLUSION: Our results support a strong association between the limited level of literacy and OS. A more in-depth study integrating variables such as socioeconomic level and location of residence would enrich these results.