Real-world overview of therapeutic strategies and prognosis of older patients with advanced or metastatic non-small cell lung cancer from the ESME database.

INTRODUCTION: In France, 40% of patients diagnosed with lung cancer are ≥70 years old, but these are under-represented in clinical trials. Using data from the French Epidemiological Strategy and Medical Economics (ESME) platform on Lung Cancer (LC), the objective is to provide an overview of the management and the prognosis of older patients with advanced or metastatic non-small cell lung cancer (AM-NSCLC) in a real-world context. MATERIALS AND METHODS: From the ESME-LC database, we selected patients with AM-NSCLC (stage IIIB, IIIC, and IV), diagnosed between 2015 and 2019, and who received first-line systemic treatment. Demographics, tumour characteristics, and treatment received were described in patients ≥70, and compared to younger ones. Real-world progression-free survival (rwPFS) and overall survival (OS) were evaluated using the multivariable Cox model. RESULTS: Among 10,002 patients with AM-NSCLC, the median age was 64 years, with 2,754 (27.5%) aged ≥70. In comparison with patients <70, older patients were more often male, with worse performance status and more comorbidities, but they were less underweight and more often non-smokers. The proportion of EGFR mutated non-squamous NSCLC was higher in older patients (25.0% vs 12.8%, p < 0.001), particularly among smokers and former smokers (12.7% vs 7.3%, p < 0.001). Among patients ≥70, 76.6% received first-line chemotherapy (including 67.0% treated with a platinum-based doublet), 15.0% received only targeted therapy, and 11.0% received immunotherapy (alone or in combination). Median first-line rwPFS was 5.1 months (95% confidence interval [CI] = [4.8;5.4]) for patients ≥70 and 4.6 months (95%CI = [4.4;4.8]) for patients <70, but age was not associated with rwPFS in multivariable analysis. Median OS was 14.8 months (95%CI = [13.9;16.1]) for patients ≥70 and 16.7 months (95%CI = [15.9;17.5]) for patients <70, with a significant effect of age in multivariable analysis for patients treated with chemotherapy and/or with targeted therapy, but not for patients treated with immunotherapy (alone or in combination with chemotherapy). DISCUSSION: In this real-world cohort of patients with AM-NSCLC, age was not associated with first-line rwPFS regardless of treatment received, nor with OS for patients receiving immunotherapy. However, OS was significantly shorter for patients aged ≥70 treated with chemotherapy or with targeted therapy alone.

The Benefit of Combining Docetaxel with Androgen Deprivation Therapy in Localized and Metastatic Hormone-sensitive Prostate Cancer is Predicted by ERG Expression: An Analysis of Two GETUG Phase 3 Trials.

BACKGROUND AND OBJECTIVE: Docetaxel has become a standard component of care for advanced prostate cancer (PC); however, its benefits are not universal among patients. A subset of PC cases exhibit TMPRSS2-ERG gene fusion, resulting in ERG overexpression in tumors. Our aim was to assess biomarkers for docetaxel efficacy in men with hormone-sensitive PC (HSPC). METHODS: Pretreatment prostate biopsies were obtained from participants in two randomized phase 3 clinical trials investigating docetaxel in high-risk localized PC (GETUG 12) and metastatic HSPC (GETUG 15). Immunohistochemistry staining for Ki67, PTEN, RB, and phosphorylated RB was conducted for GETUG 12 samples, and ERG staining for GETUG 12 and GETUG 15 samples. We examined biomarker association with outcomes using univariate and multivariable analyses adjusted for other validated prognostic factors. KEY FINDINGS AND LIMITATIONS: Among GETUG 12 patients, Ki67 was associated with a worse relapse-free survival (RFS; hazard ratio [HR] 1.72; p = 0.0092). A pooled analysis for the two trials (pinteraction = 0.056) revealed that docetaxel-based chemotherapy improved failure-free survival for patients with ERG-positive cancer (HR 0.58; p = 0.03), but not patients with ERG-negative cancer (HR 1.08; p = 0.72). In the ERG-positive subgroup in GETUG 12 (high-risk localized PC), median RFS was 7.79 yr with androgen deprivation therapy (ADT) alone, and was not reached with ADT + docetaxel. In the ERG-negative subgroup, median progression-free survival (mPFS) was 7.79 yr with ADT alone versus 7.08 yr with ADT + docetaxel. In the ERG-positive subgroup in GETUG 15 (metastatic HSPC), mPFS was 10.7 mo with ADT alone versus 18.8 mo with ADT + docetaxel. In the ERG-negative subgroup, mPFS was 10.6 mo with ADT alone versus 13.2 mo with ADT + docetaxel. CONCLUSIONS AND CLINICAL IMPLICATIONS: Ki67 may serve as a prognostic factor in HSPC, while ERG expression appears to predict a response to docetaxel in both high-risk localized and metastatic HSPC. PATIENT SUMMARY: We assessed factors that could predict outcomes after docetaxel chemotherapy in patients with advanced prostate cancer. We found that expression of a protein called ERG can predict a good response to docetaxel in these patients.

Pembrolizumab plus Abiraterone Acetate and Prednisone in Patients with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort D.

BACKGROUND AND OBJECTIVE: Abiraterone acetate (abiraterone) plus prednisone is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Our aim was to evaluate the efficacy and safety of pembrolizumab plus abiraterone in mCRPC. METHODS: In cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573), patients were chemotherapy-naïve, had disease progression ≤6 mo before screening, and had either not received prior next-generation hormonal agents for mCRPC or had received prior enzalutamide for mCRPC and had disease progression or became intolerant to enzalutamide. Patients received pembrolizumab 200 mg intravenously every 3 wk plus abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily. The primary endpoints were safety, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3-modified RECIST v1.1 by BICR and overall survival (OS). KEY FINDINGS AND LIMITATIONS: For the 103 patients who were treated, median follow-up was 28 mo (interquartile range 26-31). The confirmed PSA response rate was 56% (58/103 patients). The ORR for patients with RECIST v1.1-measurable disease was 16% (6/37 patients). Median rPFS was 15 mo (95% confidence interval 9.2-22) and median OS was 30 mo (95% confidence interval 23-not reached); the estimated 24-mo OS rate was 58%. In total, 91% of patients experienced treatment-related adverse events, and 39% experienced grade 3-5 events. Grade 3/4 elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) was observed in 12% and 6.8% of patients, respectively. One patient died due to treatment-related myasthenic syndrome. Study limitations include the single-arm design. CONCLUSIONS: Pembrolizumab plus abiraterone and prednisone demonstrated antitumor activity and acceptable safety in patients with chemotherapy-naïve mCRPC. Higher incidence of grade 3/4 elevated ALT/AST occurred than was reported for the individual agents. PATIENT SUMMARY: For patients with metastatic castratation-resistant prostate cancer, the drug combination of pembrolizumab plus abiraterone and prednisone showed antitumor activity and acceptable safety.

Myelodysplastic Syndrome Related to Successful Treatment With177Lu-PSMA for Metastatic Castration-Refractory Prostate Cancer.

ABSTRACT: 177Lu-vipivotide tetraxetan (177Lu-PSMA-617/LuPSMA) received recent EMA approval for metastatic castration-resistant prostate cancer, with promising data for earlier stages. Secondary myeloid neoplasm following exposure to DNA-damaging therapy (therapy-related myelodysplastic syndrome [MDS]) is a rare severe complication of 177Lu-oxodotreotide. We present a 77-year-old man, with synchronous liver, bone, and lymph node metastatic prostate cancer, having developed a low-risk MDS with SF3B1 mutation, 1 month after the sixth administration of LuPSMA. Although on partial metabolic and biological response with PSA nadir at 7 months after therapy, life quality was significantly altered by MDS.

PD-L1 expression and its prognostic value in metastatic papillary renal cell carcinoma: Results from a GETUG multicenter retrospective cohort.

INTRODUCTION: Papillary renal cell carcinoma (pRCC) is a rare and aggressive cancer with no specifically established therapeutic strategy in the metastatic setting. Combinations of tyrosine kinase and immune checkpoint inhibitors (ICI) are a promising option. We aimed to study the immune landscape of metastatic pRCC, and its interactions with angiogenesis pathways, to search for potential therapeutic targets. METHODS: The expression of immune markers (PD-L1, PD-1, PD-L2, LAG-3) and angiogenic pathways (CAIX, c-MET), was analyzed by immunohistochemistry on 68 metastatic pRCC retrieved from a retrospective multicenter GETUG cohort. Our primary endpoint was to estimate the prevalence of PD-L1 expression and its prognostic impact in metastatic pRCC. Secondary endpoints included the evaluation of other immune markers (PD-1, PD-L2, and LAG-3) and their association with PD-L1. We also assessed angiogenic markers and their association with PD-L1. RESULTS: Overall, 27.9 % of tumors were PD-L1 positive. PD-L2 was more frequently expressed (45.6 %), PD-1 and LAG-3 were positive in 17.6 % and 19.1 % respectively. None of these markers was correlated with PD-L1 expression. 66 % (45/68) expressed at least one immune marker, and 43 % (29/68) were "double-positive", as they expressed both immune and angiogenic markers. OS was significantly shorter for patients with PD-L1 positive pRCC. A multivariate analysis confirmed a significant association between PD-L1 expression and shorter overall survival (HR = 4.0, p = 0.01). CONCLUSION: These results reinforce clinical data on the expected benefit of ICI in metastatic pRCC treatment, as PD-L1 expression is a factor of poor prognosis in this multicenter cohort.

A Signal-Finding Study of Abemaciclib in Heavily Pretreated Patients with Metastatic Castration-Resistant Prostate Cancer: Results from CYCLONE 1.

PURPOSE: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors radically changed the treatment paradigm for breast cancer. Similar to estrogen receptor in breast cancer, androgen receptor signaling activates cyclin D-CDK4/6, driving proliferation and resistance to hormonal manipulation in prostate cancer. This study was designed to detect signals of clinical activity for abemaciclib in treatment-refractory metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Eligible patients had progressive mCRPC, measurable disease, and previously received ≥1 novel hormonal agent(s) and 2 lines of taxane chemotherapy. Abemaciclib 200 mg twice daily was administered on a continuous dosing schedule. Primary endpoint was objective response rate (ORR) without concurrent bone progression. This study was designed to detect a minimum ORR of 12.5%. RESULTS: At trial entry, 40 (90.9%) of 44 patients had objective radiographic disease progression, 4 (9.1%) had prostate-specific antigen (PSA)-only progression, and 20 (46.5%) had visceral metastases (of these, 60% had liver metastases). Efficacy analyses are as follows: ORR without concurrent bone progression: 6.8%; disease control rate: 45.5%; median time to PSA progression: 6.5 months [95% confidence interval (CI), 3.2-NA]; median radiographic PFS; 2.7 months (95% CI, 1.9-3.7); and median OS, 8.4 months (95% CI, 5.6-12.7). Most frequent grade ≥3 treatment-emergent adverse events (AE) were neutropenia (25.0%), anemia, and fatigue (11.4% each). No grade 4 or 5 AEs were related to abemaciclib. CONCLUSIONS: Abemaciclib monotherapy was well tolerated and showed clinical activity in this heavily pretreated population, nearly half with visceral metastases. This study is considered preliminary proof-of-concept and designates CDK4/6 as a valid therapeutic target in prostate cancer.

Safety and efficacy of nivolumab in elderly patients with metastatic clear cell renal cell carcinoma: Analysis of the NIVOREN GETUG-AFU 26 study.

INTRODUCTION: Immune checkpoint inhibitors are standard of care in metastatic renal cell carcinoma but their activity and safety in elderly patients is insufficiently explored. We evaluated outcomes of elderly patients with mRCC treated with nivolumab in the GETUG-AFU 26 NIVOREN phase 2 trial (NCT03013335) and conducted exploratory circulating biomarker analyses. METHODS: Patients with mRCC were treated with nivolumab after at least one antiangiogenic therapy. The main endpoint of this analysis was safety in patients ≥ 70 years old (y.o), as per the rate of treatment-related grade 3-5 events (TRAE). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival. Exploration of candidate biomarkers associated with aging included baseline circulating cytokines involved in inflammation, adhesion, immune checkpoints, angiogenesis (IL6, IL7, IL8, BAFF, CXCL13, VCAM-1, 4-1BB, VEGF). RESULTS: Of 720 patients, 515 were < 70 y.o and 205 ≥ 70 y.o. Patients ≥ 70 y.o exhibited numerically less IMDC poor risk disease (21.0% vs 26.9%), sarcomatoid component (4.9% vs 9.8%) or brain metastases (5.9% vs. 14.7%), but more previous treatment lines (≥ 2 in 54.1% vs 48.5%). TRAE were higher in patients ≥ 70 y.o (24.9% vs. 17.9%, p = 0.033). Respective ORR (19.2% vs. 22.1%) and median PFS (4.5 versus 3.0 months, HR 0.97 [95%CI 0.81-1.15]) were similar. Overall survival was shorter in patients ≥ 70 y.o (19.3 versus 26.9 months, HR 1.26 [95%CI 1.04-1.51]), but not significantly in a competitive risk model. Only V-CAM1 and 4-1BB were found to be increased in patients ≥ 70 y.o. CONCLUSIONS: Nivolumab displayed higher grade 3/4 TRAE but manageable toxicity in elderly patients, with sustained activity. Elderly patients did not display specific inflammatory or angiogenic circulating profiles.

Exposure-response relationship of cabozantinib in patients with metastatic renal cell carcinoma treated in routine care.

BACKGROUND: Interindividual pharmacokinetic variability may influence the clinical benefit or toxicity of cabozantinib in metastatic renal cell carcinoma (mRCC). We aimed to investigate the exposure-toxicity and exposure-response relationship of cabozantinib in unselected mRCC patients treated in routine care. METHODS: This ambispective multicenter study enrolled consecutive patients receiving cabozantinib in monotherapy. Steady-state trough concentration (Cmin,ss) within the first 3 months after treatment initiation was used for the PK/PD analysis with dose-limiting toxicity (DLT) and survival outcomes. Logistic regression and Cox proportional-hazards models were used to identify the risk factors of DLT and inefficacy in patients, respectively. RESULTS: Seventy-eight mRCC patients were eligible for the statistical analysis. Fifty-two patients (67%) experienced DLT with a median onset of 2.1 months (95%CI 0.7-8.2). In multivariate analysis, Cmin,ss was identified as an independent risk factor of DLT (OR 1.46, 95%CI [1.04-2.04]; p = 0.029). PFS and OS were not statistically associated with the starting dose (p = 0.81 and p = 0.98, respectively). In the multivariate analysis of PFS, Cmin, ss > 336 ng/mL resulted in a hazard ratio of 0.28 (95%CI, 0.10-0.77, p = 0.014). By contrast, Cmin, ss > 336 ng/mL was not statistically associated with longer OS. CONCLUSION: Early plasma drug monitoring may be useful to optimise cabozantinib treatment in mRCC patients treated in monotherapy, especially in frail patients starting at a lower than standard dose.

Pembrolizumab and Enzalutamide in Patients with Abiraterone Acetate-Pretreated Metastatic Castration-Resistant Prostate Cancer: Cohort C of the Phase 1b/2 KEYNOTE-365 Study.

BACKGROUND: Limited responses have been observed in patients treated with enzalutamide after disease progression on abiraterone for metastatic castration-resistant prostate cancer (mCRPC), but androgen receptor signaling impacts T-cell function. OBJECTIVE: To evaluate the efficacy and safety of pembrolizumab plus enzalutamide in mCRPC. DESIGN, SETTING, AND PARTICIPANTS: Patients in cohort C of the phase 1b/2 KEYNOTE-365 study, who received ≥4 wk of treatment with abiraterone acetate in the prechemotherapy mCRPC state and experienced treatment failure or became drug-intolerant, were included. INTERVENTION: Pembrolizumab 200 mg intravenously every 3 wk plus enzalutamide 160 mg orally once daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were safety, the confirmed prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 on blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) on BICR and overall survival (OS). RESULTS AND LIMITATIONS: A total of 102 patients received pembrolizumab plus enzalutamide. Median follow-up was 51 mo (interquartile range 37-56). The confirmed PSA response rate was 24% (95% confidence interval [CI] 16-33%). The confirmed ORR was 11% (95% CI 2.9-25%; 4/38 patients; two complete responses). Median rPFS was 6.0 mo (95% CI 4.1-6.3). Median OS was 20 mo (95% CI 17-24). Treatment-related adverse events (TRAEs) occurred in 94 patients (92%); grade 3-5 TRAEs occurred in 44 patients (43%). The incidence of treatment-related rash was higher with combination therapy than expected from the safety profile of each drug. One patient (1.0%) died of a TRAE (cause unknown). Study limitations include the single-arm design. CONCLUSIONS: Pembrolizumab plus enzalutamide had limited antitumor activity in patients who received prior abiraterone treatment without previous chemotherapy for mCRPC, with a safety profile consistent with the individual profiles of each agent. PATIENT SUMMARY: Pembrolizumab plus enzalutamide showed limited antitumor activity and manageable safety in patients with metastatic castration-resistant prostate cancer. The KEYNOTE-365 trial is registered on ClinicalTrials.gov as NCT02861573.

Surgery with or Without Darolutamide in High-risk and/or Locally Advanced Prostate Cancer: The SUGAR (CCAFU-PR2) Phase 2 Trial Rationale and Protocol.

BACKGROUND: High-risk prostate cancer (PCa) patients frequently experience recurrence and progression after radical prostatectomy (RP). Neoadjuvant androgen deprivation therapy (ADT) has not demonstrated a clear oncological benefit and is not currently recommended. OBJECTIVE: The SUGAR trial is the first phase 2, randomised, controlled, multicentre, noncommercial, open-label study investigating single-agent perioperative darolutamide compared with the standard of care (ie, upfront RP, without neoadjuvant ADT). DESIGN, SETTING, AND PARTICIPANTS: SUGAR aims to randomise 240 men affected by nonmetastatic PCa, with the major eligibility criteria being International Society of Urological Pathology grade group ≥4, seminal vesicle invasion at magnetic resonance imaging and/or clinically node-positive disease. Patients in the experimental arm will undergo neoadjuvant darolutamide monotherapy, RP, and adjuvant darolutamide, completing 9 mo of treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint is noncurable recurrence-free survival, an innovative and clinically meaningful measure; the secondary endpoints encompass safety; recurrence-free, metastasis-free, and overall survival; pathological response; and quality of life. A predictive biomarker analysis will also be performed. RESULTS AND LIMITATIONS: Initial data suggest that intensified neoadjuvant treatment with androgen receptor signalling inhibitors (ARSIs) is associated with a sustained pathological response and may improve outcomes, via tumour downstaging and micrometastasis eradication. ARSI monotherapy could further enhance tolerability. CONCLUSIONS: SUGAR will provide efficacy and safety information on perioperative darolutamide monotherapy compared with upfront RP, in a contemporary high-risk PCa population undergoing surgery. PATIENT SUMMARY: The on-going SUGAR clinical trial evaluates 9 mo of darolutamide treatment in addition to radical prostatectomy, in men affected by prostate cancer with specific high-risk characteristics. It investigates whether this hormonal treatment can lower the rates of noncurable recurrences, maintaining a favourable tolerability profile.

Very Long-Term Complete Remission Can Be Achieved in Men With High-Risk Localized Prostate Cancer and a Very High PSA Value: An Analysis of the GETUG 12 Phase 3 Trial.

INTRODUCTION: Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established. PATIENTS AND METHODS: Ancillary analysis from the GETUG 12 phase 3 trial. Patients with non-metastatic high-risk prostate cancer by bone and computerized tomography (CT) scan were randomly assigned to receive androgen deprivation therapy (ADT) and docetaxel plus estramustine or ADT alone. Relapse-free survival (RFS), clinical RFS, metastases-free survival (MFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using the Kaplan-Meier method for different levels of PSA (50 ng/mL, 75 ng/mL, and 100 ng/mL). The relationship between PSA and outcomes was studied using residual-based approaches and spline functions. RESULTS: The median follow-up was 12 years (range: 0-15.3). Baseline PSA (<50 ng/mL, n = 328; ≥50ng/mL, n = 85) was associated with improved RFS (P = .0005), cRFS (P = .0024), and MFS (P = .0068). The 12-year RFS rate was 46.33% (CI 40.59-51.86), 33.59% (CI 22.55-44.97), and 11.76% (1.96-31.20) in men with PSA values <50 ng/mL (n = 328), 50-100 ng/mL (n = 68), and ≥100 ng/mL (n = 17), respectively. Exploratory analyses revealed no deviation from the linear relationship assumption between PSA and the log hazard of events. CONCLUSIONS: Men with apparently localized prostate cancer and a high baseline PSA value have a reasonable chance of being long-term disease-free when treated with curative intent combining systemic and local therapy.

Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in the Treatment of Advanced Renal Cancer.

Seven tyrosine kinase inhibitor compounds with anti-angiogenic properties remain key drugs to treat advanced renal cell carcinoma. There is a strong rationale to develop therapeutic drug monitoring for these drugs. General considerations of such monitoring of the several groups of anticancer drugs are given, with a focus on oral therapy. Pharmacokinetics and the factors of inter- and intraindividual variabilities of these tyrosine kinase inhibitors are described together with an exhaustive presentation of their pharmacokinetic/pharmacodynamic relationships. The latter was observed in studies where every patient was treated with the same dose, and the results of several prospective studies based on dose individualization support the practice of increasing individual dosage in case of low observed plasma drug concentrations. Finally, the benefits and limits of therapeutic drug monitoring as a routine practice are discussed.

Outcomes of comprehensive geriatric assessment and surgical management in head and neck cancers of the elderly: an observational study.

AIM: The aims of this study were to assess the survival benefit of optimal vs suboptimal management in elderly patients presenting with upper aerodigestive tract (UADT) cancer for which surgery was the standard of care, and determine if comprehensive geriatric assessment (CGA) was a prognostic factor for survival. MATERIALS AND METHODS: This single-center retrospective cohort study was conducted from January 2014 to December 2018. Included patients were aged 70 or older at the time of diagnosis, and presented with UADT cancer with a theoretical indication for curative-intent surgery according to international guidelines. RESULTS: A total of 188 patients were included, with a median age of 78 years. Treatment included surgery in 67.6% of cases and was considered optimal in 60.6% of patients. The overall 3-year survival was 55.2%, and was significantly better in case of optimal vs suboptimal treatment (74.5% vs 25.8%, p < 0.001). In univariate analysis, factors associated with a significantly improved 3-year survival included surgery (p < 0.001), age < 80 years, performance status < 2 and G8 score > 14. In multivariate analysis, CGA was associated with a better survival. CONCLUSIONS: In patients aged over 70 presenting with UADT cancer for which the standard of care is surgery, an optimal management is associated with better overall survival. Receiving a CGA seems to provide a survival benefit in patients with a G8 score ≤ 14, through an optimization of the care pathway before and after the cancer treatment.

[Rethinking the management of elderly cancer patients : Proposals from the Age Cancer Priorities French Group]. / Repenser la prise en charge des sujets âgés atteints d'un cancer : propositions du groupe Priorités Âge Cancer.

The growing incidence of cancer associated with an aging population implies important health challenges that require questioning on the care management of older adults with cancer. There is a need to rethink the care management of older cancer patients with patient-centered decisions and an adjustment of the care pathway for this population. The Priorities Age Cancer (PAC) French group, made up of physicians, pharmacists and researchers in geriatric oncology, set up proposals to answer this need. First, the heterogeneity and the specificities of older adults as well as their preferences regarding cancer treatment goals, care management decisions must be patient-centered. The frailty screening tools should be generalized in clinical practice to provide geriatric assessment-guided recommendations and help for treatment decisions, and patients' involvement and shared decision should be developed. Second, older adults with cancer confront a complex health care system that demands a high level of health literacy. The caregivers, playing an essential role, may not be prepared for all these challenges. Thus, there is a need to promote health literacy by patient education, and patient-experts should be involved in health pathway. Third, there is a need to deal with dedicated partners and adjust the care pathway. New pathway careers as case-management nurses and specialized pharmacists should be involved in patient care and may play a central role together with other careers. Community-Hospital coordination should also be reinforced.

Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study.

BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments. OBJECTIVE: To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC. DESIGN, SETTING, AND PARTICIPANTS: The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening. INTERVENTION: Pembrolizumab 200 mg intravenously (IV) every 3 wk (Q3W), docetaxel 75 mg/m2 IV Q3W, and prednisone 5 mg orally twice daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were safety, the prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included time to PSA progression; the disease control rate (DCR) and duration of response (DOR) according to RECIST v1.1 by BICR; ORR, DCR, DOR, and radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3-modified RECIST v1.1 by BICR; and overall survival (OS). RESULTS AND LIMITATIONS: Among 104 treated patients, 52 had measurable disease. The median time from allocation to data cutoff (July 9, 2020) was 32.4 mo, during which 101 patients discontinued treatment, 81 (78%) for disease progression. The confirmed PSA response rate was 34% and the confirmed ORR (RECIST v1.1) was 23%. Median rPFS and OS were 8.5 mo and 20.2 mo, respectively. Treatment-related adverse events (TRAEs) occurred in 100 patients (96%). Grade 3-5 TRAEs occurred in 46 patients (44%). Seven AE-related deaths (6.7%) occurred (2 due to treatment-related pneumonitis). Limitations of the study include the single-arm design and small sample size. CONCLUSIONS: Pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC treated with abiraterone or enzalutamide for mCRPC. Safety was consistent with profiles for the individual agents. Further investigation is warranted. PATIENT SUMMARY: We evaluated the efficacy and safety of the anti-PD-1 antibody pembrolizumab combined with the chemotherapy drug docetaxel and the steroid prednisone for patients with metastatic prostate cancer resistant to androgen deprivation therapy , and who never received chemotherapy. The combination showed antitumor activity and manageable safety in this patient population. This trial is registered on ClinicalTrials.gov as NCT02861573.

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.

BACKGROUND: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care. METHODS: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436. FINDINGS: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone. INTERPRETATION: Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients. FUNDING: Janssen-Cilag, Ipsen, Sanofi, and the French Government.

Spreading geriatric oncology culture through professional caregivers: Results of a French massive open online course (MOOC).

Geriatric oncology is based on the synergy between several professionals whose common goal is to improve care for older patients with cancer. This requires sharing a common core of knowledge to facilitate collaboration between them. To date, training in geriatric oncology has been limited in scope and difficult to access for caregivers, particularly nurses and healthcare aides. To meet this need, a massive open online course (MOOC), in geriatric oncology has been developed in France. This kind of course aims to provide simultaneous access for a large number of participants and to foster communication with the pedagogical team through discussion forums. The first session of the MOOC, which has been set up in the Occitania region of France, went online nationwide from March 6 to June 23, 2020. Despite the SARS CoV-2 global health crisis, 1020 people subscribed to the first session and 417 (40.9%) were certified at the end of the course. Most are nurses (35.2%) and work outside Occitania (56.3%). A survey revealed a high satisfaction level regarding relevance of lessons (97.9%), pedagogical quality of teaching team (97.9%), knowledge acquisition (93.6%), meeting learners' needs (90.4%) and practical value of the course (88.3%). This preliminary experience demonstrates the ability of this MOOC to spread the culture of geriatric oncology and the educational potential of this new type of online training.

[Development and assessment of a MOOC about delirium in geriatric oncology]. / Création et évaluation d'un MOOC sur le syndrome confusionnel en oncogériatrie.

INTRODUCTION: Among the themes to be addressed by a Massive Open Online Course (MOOC) on geriatric oncology, one of the priorities was delirium, due to its frequency, complications and difficulties encountered by healthcare professionals in diagnosing and managing delirium. Our study aims to evaluate professional practices in the area of education, regarding the evaluation of the content of a MOOC module about delirium syndrome in geriatric oncology. METHODS: We created a multidisciplinary group to define the scientific content, the pedagogical objectives, the scriptwriting and the development of a training module. The quality of instructional design was then evaluated according to eleven MOOC design principles to promote learning. Participants were studied. RESULTS: Seven of the eleven criteria for evaluating pedagogical quality were documented. Among the 1020 participants, 455 (44.6%) completed the final test concerning delirium: 417 (40.8%) passed the final test; 406 documented their profession and the region of France where they worked: 146 (32%) nurses (confirming the participation of the targeted audience), 103 (22.6%) doctors/pharmacists (illustrating the multi-professional interest of the thematic), with a wide distribution of the participants over the national territory. DISCUSSION: The multidisciplinary team's investment in developing these teaching materials strengthened the group's cohesion and valuated its professional skills. All teaching resources developed for access via the internet must be accompanied by an evaluation of the quality of the scientific content, objectives and teaching methods, before being able to appreciate its use in the field and assess its real impact on the participants' learning and practice.