[PARP inhibitors - A better selection of patients]. / Inhibiteurs de la PARP : une meilleure sélection des patient-e-s.

PARP inhibitors (PARPi) have established themselves as a class of essential anti-cancer drugs. They inhibit PARP proteins involved in DNA damage repair. Their anti-tumor action requires a concomitant abnormality in DNA damage repair, the homologous recombination deficiency (HRD). The genomic instability being too substantial, the tumor cell goes into apoptosis (concept of synthetic lethality). This last decade, the selection of patients benefiting from PARPi has been refined with convincing results for ovarian cancers, but also breast, prostate and pancreatic cancers. This article presents recent data that have impacted our clinical practice and the PARPi authorized in Switzerland.

Les inhibiteurs de la PARP (poly-ADP-ribose-polymérase : iPARP) se sont imposés comme une classe de médicaments anticancéreux incontournable. Ils inhibent les protéines PARP impliquées dans la réparation de l'ADN. Leur action antitumorale nécessite une anomalie concomitante dans la réparation de l'ADN, le déficit de recombinaison homologue (HRD). L'instabilité génomique devenant trop conséquente, la cellule tumorale entre en apoptose (concept de synthetic lethality). La sélection des patient-e-s bénéficiant des iPARP s'est affinée cette dernière décennie avec des résultats probants pour les cancers de l'ovaire, mais aussi du sein, de la prostate et du pancréas. Cet article présente les données récentes ayant impacté notre pratique clinique et les iPARP autorisés en Suisse.

Patients' experiences with cancer care in Switzerland: Results of a multicentre cross-sectional survey.

OBJECTIVES: The objectives were to describe patients' experiences of cancer care in Switzerland and explore the variation of these experiences by type of cancer. METHODS: The Swiss Cancer Patient Experiences (SCAPE) study was a cross-sectional, multicentre survey conducted in 2018. Adult patients (n = 7145) with breast, prostate, lung, colorectal, skin or haematological cancer from four large hospitals in French-speaking Switzerland were invited to complete a survey. Logistic regressions were used to assess whether experiences varied according to cancer type, adjusting for confounders. RESULTS: Of the 3121 persons who returned the survey (44% response rate), 2755 reporting an eligible cancer were included in the analyses. Participants' average score for overall care was 8.5 out of a maximum score of 10. Higher rates of positive experiences were found for nurse consultations (94%), diagnostic tests (85%) and inpatient care (82%). Lower positive responses were reported for support for people with cancer (70%), treatment decisions (66%), diagnosis (65%) and home care (55%). We observed non-systematic differences in experiences of care by cancer type. CONCLUSIONS: This large study identified that cancer patient experiences can be improved in relation to communication, information and supportive care aspects. Improvement efforts should target these areas of care to enhance responsiveness of cancer care.

Quality of life and pain in patients with metastatic bone disease from solid tumors treated with bone-targeted agents- a real-world cross-sectional study from Switzerland (SAKK 95/16).

BACKGROUND: Bone-targeted agents (BTAs) are widely used in the management of patients with bone metastases from solid tumors. Knowledge of the impact of their routine care use on patient-reported pain and bone pain-related quality of life (QoL) is limited. METHODS: This real world, cross-sectional study enrolled patients over a 3-month period through oncologists across Switzerland. Patients were ≥ 18 years, had solid tumors and at least one bone metastasis, and received routine care for bone metastases. Physicians provided data on BTA-related practices, risk of bone complications and BTA regimen. Patients completed questionnaires about pain (BPI-SF), general and bone pain-related QoL (FACT-G, FACT-BP) and treatment satisfaction (FACIT-TS-G). RESULTS: Eighteen sites recruited 417 patients. Based on the FACT-BP, 42% of the patients indicated not having bone pain. According to the BPI-SF, 28% reported no, 43% mild, 14% moderate, and 15% severe pain, respectively. Patients not treated with a BTA had better overall QoL (FACT-G: p = 0.031) and bone pain-related QoL (FACT-BP, p = 0.007) than those treated with a BTA. All pain and other QoL scales did not differ between groups. Patients perceived at 'low risk of bone complications' by their physician not receiving a BTA reported less pain and better QoL than those considered at 'low risk' but receiving BTA treatment or those considered at 'high risk' regardless of BTA treatment. Overall satisfaction with the treatment was good; almost 50% of patients reporting that they were completely satisfied. CONCLUSIONS: Overall, pain and QoL did not differ according to BTA treatment or physicians' risk perception. Patient with low risks not receiving BTA treatment reported least pain and highest QoL scores. These results may suggest that treating physicians assess bone complication risk appropriately and treat patients accordingly, but they need to be confirmed by objective determination of longitudinal skeletal complication risk.

[Immunotherapy with immune checkpoint inhibitor and skin toxicity]. / Immunothérapie par inhibiteurs de points de contrôle immunitaire et toxicité dermatologique.

Dermatologic toxicities appear to be the most prevalent immunotherapy related adverse effects, both with anti-PD-1 and anti-CTLA-4 agents, as well as with the newly developed anti-PD-L1. They occur in more than one-third of the patients treated with immune check point inhibitors, regardless of the cancer being treated. They mainly manifest in the form of self-limiting maculopapular rashes and pruritus. Early recognition and management are essential in order to mitigate the severity of the lesions. A multidisciplinary team is crucial for optimal management.

Les toxicités cutanées sont les effets indésirables les plus fréquents des inhibiteurs des points de contrôle immunitaire, que ce soit avec les anti-Programmed Cell Death 1, les anti-Cytotoxic T Lymphocyte Antigen-4 ou les nouveaux anti-Programmed Cell Death-Ligand 1. Ils surviennent chez plus d'un patient sur trois, et ce quel que soit le cancer traité. Ils se manifestent le plus souvent par un rash maculopapuleux limité au niveau du tronc et des membres et un prurit. Des toxidermies graves (syndromes de Lyell, de Stevens-Johnson ou d'hypersensibilité médicamenteuse) ainsi que des dermatoses autoimmunes (maladies bulleuses, lupus érythémateux disséminé) sont plus rares, mais leur reconnaissance et leur prise en charge précoces sont essentielles. Une évaluation multidisciplinaire est, dans ces cas, souvent indispensable pour une prise en charge optimale de la toxicité et ne pas prétériter la poursuite du traitement.

[Immunotherapy with immune checkpoint inhibitors and hepatitis]. / Immunothérapie par inhibiteurs de points de contrôle immunitaire et hépatite.

Immunotherapy, with « checkpoint ¼ inhibitors (CPIs), has become an essential therapeutic weapon against cancer. Autoimmune disorders related to overactivation of the immune system are well known side effects. The risk of reactivation of the hepatitis B and C viruses and exacerbation of the hepatitis, known from the introduction of immunosuppressive drugs such as chemotherapy, is poorly documented under immunotherapy. In this article, we discuss the issue of immunotherapy in patients presented with hepatitis using two approaches: the risks of immunotherapy in these situations and the management by disruption of liver tests under immunotherapy.

L'immunothérapie, avec les inhibiteurs de points de contrôle immunitaire « immune checkpoint inhibitors ¼, est devenue une arme thérapeutique essentielle contre de nombreux cancers. Les troubles autoimmuns liés à la suractivation du système immunitaire sont des effets secondaires bien connus. Le risque de réactivation des virus de l'hépatite B et C ou d'exacerbation de l'hépatite, connu lors de l'introduction de médicaments immunosuppresseurs telles les chimiothérapies, est peu documenté sous immunothérapie. Dans cet article, nous aborderons la question de l'immunothérapie chez des patients présentant une hépatite B ou C selon deux approches : les risques encourus à introduire une immunothérapie dans ces situations et la gestion d'une perturbation des tests hépatiques sous immunothérapie.

Locoregional Control and Toxicity in Head and Neck Carcinoma Patients following Helical Tomotherapy-Delivered Intensity-Modulated Radiation Therapy Compared with 3D-CRT Data.

OBJECTIVES: To assess the feasibility and efficacy of intensity-modulated radiation implemented with helical tomotherapy image-guided with daily megavoltage computed tomography for head and neck cancer. METHODS: Between May 2010 and May 2013, 72 patients were treated with curative intent. The median age was 64 years, with 57% undergoing definitive and 43% postoperative radiotherapy. Primary tumour sites were oral cavity (21%), oropharynx (26%), hypopharynx (20%), larynx (22%), and others (11%). Staging included 4% stage I, 15% II, 26% III, 48% IVa, and 7% IVb. Radiotherapy was combined with chemotherapy in 64%. Primary endpoint was locoregional control, and secondary endpoints survival and toxicity. RESULTS: Median follow-up was 20 months, with 11 locoregional recurrences. Three-year disease-free survival was 58% and overall survival 57%. In the multivariate analysis, age under 64 years, no extracapsular extension, postoperative radiotherapy, induction chemotherapy, and non-oral cavity tumour were significant favourable prognostic factors for disease-free-survival. The overall incidence of acute grade ≥3 toxicities were mucositis 32%, pain 11%, xerostomia 7%, dysphagia 53%, radiodermatitis 44%, and osteonecrosis 1%. Late grade ≥3 toxicities were fibrosis 6%, dysphagia 21%, fistula 1%, and skin necrosis 1%. CONCLUSIONS: Intensity-modulated radiation with helical tomotherapy achieved respectable locoregional control and overall survival, with acceptable toxicity, in head and neck cancer patients.

[Hemolytic anemia in cancer]. / Anémie hémolytique dans le contexte de cancer.

Hemolysis (from the Greek word: hemolysis: hema = blood + lysis = liberation) is a medical term that describes red blood cell's destruction by mechanisms of lysis of the membrane. An hemolytic anemia occurs when excessive destruction of red blood cells overwhelms bone marrow's capacity of regeneration. Although anemia is frequently associated with an oncologic disease, hemolytic anemia is rarely diagnosed in oncologic patients. Consequently, a massive hemolysis can be quickly deleterious and often fatal. An early diagnosis can improve survival and can be made with inexpensive tests. In this article, we present the different types of hemolytic anemia associated with oncologic diseases, their mechanism and the treatment propositions depending on the etiology.

Une hémolyse (du mot grec : hémolysis : héma = sang + lysis = libération) est un terme médical qui décrit la destruction des globules rouges par des mécanismes de lyse de leur membrane. Une anémie hémolytique survient quand la destruction excessive des globules rouges dépasse la capacité régénérative de la moelle osseuse. Pourtant, alors qu'une anémie non hémolytique est fréquemment associée à une maladie oncologique, une anémie hémolytique est rarement diagnostiquée parmi les patients oncologiques. Cependant, une hémolyse massive peut être rapidement délétère et souvent mortelle. Son diagnostic précoce améliore la survie et peut être posé avec des examens peu coûteux. Dans cet article, nous présentons les différents types d'anémie hémolytique associée à des maladies oncologiques, leur mécanisme ainsi que les traitements proposés en fonction de l'étiologie.

[Oncology trajectories of elderly patients in a palliative situation : « The long and winding road ¼]. / Trajectoires oncologiques de personnes âgées en situation palliative: « The long and winding road ¼.

This paper focuses on trajectories of elderly patients with metastatic cancer who experience several lines of systemic palliative cancer treatments. Based on photographs representing paths, the representations between patients and professional caregivers vary. Where the latter see wearisome treatments and spaces of negotiation, the patients wish to be seen as fighters, a figure that ought to be adopted to face cancer and its treatments, day after day, to meet medical and social expectations.

Cet article s'intéresse aux trajectoires des personnes âgées atteintes de cancer métastatique qui font l'expérience de plusieurs lignes de traitements oncologiques systémiques palliatifs. Sur la base d'un choix de photos évoquant des parcours, les représentations entre les patients et les soignants diffèrent. Là où ces derniers voient la pénibilité des traitements et des espaces de négociation, les patients veulent être appréhendés comme des battants, figure qu'il convient d'adopter pour faire face au cancer et aux traitements, jour après jour, et correspondre aux attentes médicales et sociales.

[Renal toxicities in oncology therapies]. / Néphrotoxicité des thérapies oncologiques.

Development of oncological treatments has progressively and significantly reduced both mortality and morbidity. Chemotherapy and more recently immunotherapy may have short- and long-term side effects among which, renal involvement is one of the most frequent complications, which may alter therapeutic options and quality of life. High cumulative doses of chemotherapy, concomitant administration of nephrotoxic treatment and pre-existing nephropathy are to be carefully considered. This article intends to review some practical considerations concerning therapies from a nephrological point of view.

Le développement de thérapies oncologiques spécifiques a permis de diminuer progressivement et significativement la mortalité ainsi que la morbidité globale. La chimiothérapie et plus récemment les traitements biologiques ciblés peuvent s'accompagner d'effets secondaires à court et long termes, et l'atteinte rénale est l'une des complications les plus fréquentes qui peut notamment limiter significativement les options thérapeutiques et la qualité de vie des patients. Les doses cumulées de ces traitements, l'administration simultanée de traitements néphrotoxiques et la présence de néphropathies concomitantes sont des éléments à prendre en considération. Cet article propose de revoir quelques aspects pratiques sur le plan néphrologique concernant certaines thérapies oncologiques.

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial.

BACKGROUND: Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. METHODS: This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. RESULTS: Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15-35 %) and arm B (24 % [16/68]; 95 % CI 13-34 %; P = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46-0.69) and 50 % (37/74; 95 % CI 0.39-0.61) in arms A and B, respectively (P = 0.45). Median PFS was 10.3 months (95 % CI 8.7-11.3) in arm A and 8.5 months (95 % CI 6.5-11.9) in arm B (P = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. CONCLUSION: This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3-5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine.

[Diarrhea caused by systemic anti-cancer treatments]. / Diarrhées provoquées par les traitements systémiques anticancéreux.

Diarrhea is one of the most common complaints in oncologic patients. Causes are multiple including bowel resection, infections, radiation and systemic anti-cancer treatments. In the latter case, the pathophysiology is partially elucidated and requires the etiology to be precisely identified : chemotherapy, targeted therapy or immunotherapy. Loperamide remains central in uncomplicated cases. However, with development of immunotherapy, autoimmune mechanism should be recognized and requires different approach based mainly on corticosteroids. Physician taking care of patients with diarrhea should therefore identify possible causes in order to offer adapted treatments and therefore reduce morbidity and mortality.

Les diarrhées sont l'une des plaintes les plus fréquentes chez les patients oncologiques. On retrouve des étiologies multiples comme la résection digestive, les infections, la radiothérapie et les traitements anticancéreux systémiques. Dans ce dernier cas, la pathophysiologie est partiellement élucidée et nécessite d'en différencier l'étiologie : chimiothérapie, thérapie ciblée ou immunothérapie. Le lopéramide reste le traitement standard des cas non compliqués. Avec le développement de l'immunothérapie, un mécanisme auto-immun doit être reconnu car il nécessite une prise en charge différente reposant principalement sur l'utilisation des corticoïdes. Le médecin faisant face à un patient présentant une diarrhée doit de ce fait identifier la ou les causes possibles et ainsi adapter le traitement afin d'en réduire la morbidité et la mortalité.

Efficacy and tolerability of two scalp cooling systems for the prevention of alopecia associated with docetaxel treatment.

PURPOSE: Chemotherapy-induced alopecia is very distressing for a patient and may have an impact on treatment decisions. On docetaxel-based therapy, alopecia occurs in a substantial proportion of patients. We aimed to investigate whether two different methods of scalp cooling can prevent hair loss. METHODS: In this open-label, prospective, nonrandomized trial, patients with solid tumors receiving docetaxel in a palliative setting were allocated according to patients' preference to short-term cooling (over 45 min postinfusion) with a Paxman PSC-2 machine (PAX), with cold cap (CC), or no cooling. The combined endpoint was alopecia World Health Organisation (WHO) III or IV or the necessity to wear a wig. Study identifier is Clinicaltrials.gov NCT01008774. RESULTS: Two hundred thirty-eight patients were included in the trial (128 patients PAX, 71 CC, and 39 no cooling). Number of cycles (median 4) and median docetaxel doses were similar across groups (55-60 mg/day on weekly therapy, 135-140 mg/day on 3-weekly therapy). Alopecia occurred with PAX, CC, and no cooling under 3-weekly docetaxel in 23, 27, and 74% and under weekly docetaxel in 7, 8, and 17%, respectively. Overall, cooling (PAX and CC combined) reduced risk of alopecia by 78% (hazard ratio 0.22; 95% confidence interval 0.12 to 0.41). CC and PAX prophylaxis led to the same degree of prevention of alopecia. Adverse events (AE) were reported in 5% (most frequently, sensation of cold), and 30 patients (13%) discontinued cooling measures after cycle 1. CONCLUSIONS: In this first comparison published to date, both PAX and CC offer efficacious protection against hair loss, in particular when docetaxel is administered in a 3-weekly interval.

Deep and lasting response and acquired resistance to BRAFV600E targeting in a low-grade ovarian cancer patient.

The treatment of BRAFV600E mutant melanoma has been revolutionized by BRAF inhibitors. Furthermore, the BRAF/MEK combination has shown further improvement in clinical outcomes in advanced and in adjuvant melanoma patients. In low-grade ovarian tumors, BRAF inhibitor use has been also proposed. Here we present a patient with an excellent, lasting response to BRAF therapy alone. At first progression, after more than two years on BRAF monotherapy, we could not identify any molecular mechanisms explaining resistance. After a switch to dual BRAF/MEK therapy, the patient responded. However, despite the initial response clinical the patient again progressed, this time with the appearance of a KRAS G12C mutation, which could not be overcome by BRAF/MEK therapy. We provide evidence that BRAF inhibitor alone can be highly beneficial in BRAF mutant low-grade ovarian tumors and the resistance mechanisms are similar to that of other BRAF mutant tumors, including in melanoma.

Quality of life, effectiveness, and safety of aflibercept plus FOLFIRI in older patients with metastatic colorectal cancer: An analysis of the prospective QoLiTrap study.

INTRODUCTION: Colorectal cancer (CRC) mainly affects older patients. The pivotal VELOUR phase III trial of aflibercept plus FOLFIRI in metastatic CRC (mCRC) included only 5.9% of patients aged ≥75 years. Herein, we report a preplanned analysis from QoLiTrap, a large prospective observational study evaluating the impact of age on quality of life (QoL), effectiveness, and safety of aflibercept plus FOLFIRI in daily clinical practice in Europe. MATERIALS AND METHODS: Enrolled patients had progressive mCRC, had failed a prior oxaliplatin-based regimen, and had received aflibercept (4 mg/kg) plus FOLFIRI every two weeks until disease progression, death, unacceptable toxicity, or physician/patient decision. Analyses were performed by age classes (<60, 60-64, 65-69, 70-74, and ≥ 75 years). The primary endpoint was the percentage of patients whose global health status (GHS) of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was maintained (i.e., no worsening from baseline by at least 5% over a 12-week treatment). Secondary endpoints included tumor objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Overall, 1277 patients (<60 years, n = 327; 60-64 years, n = 231; 65-69 years, n = 227; 70-74 years, n = 259; and ≥ 75 years, n = 233) were treated, of whom 872 were evaluable for QoL. GHS was maintained in 36.5%, 41.6%, 38.9%, 41.8%, and 44.8% of patients aged <60, 60-64, 65-69, 70-74, and ≥ 75 years, respectively. Age did not influence PFS (median 7.8 months), OS (median 14.4 months), or ORR (20.8%). Number of cycles, dose delays for any cause, and dose reductions for adverse events (AEs) were comparable between age classes. Grade ≥ 3 AEs occurred in 47.7%, 51.9%, 51.5%, 55.2%, and 55.8% of patients aged <60, 60-64, 65-69, 70-74, and ≥ 75 years, respectively. The main grade ≥ 3 AEs were hypertension (11.2%) and diarrhea (9%) in patients aged ≥75 years. DISCUSSION: The results suggest that aflibercept plus FOLFIRI maintains QoL and retains its activity, including a high objective tumor response, regardless of age and treatment line. In fit older patients, the safety profile seems manageable, with no new safety signals.

[Differenciated thyroid cancer: management and indication of the new targeted therapies]. / Cancers différenciés de la thyroïde: prise en charge et place des nouvelles thérapies ciblées.

The emergence of the new targeted therapies has revolutionized the management of several cancers. We take a special interest in the standard management of all thyroid cancer, except the anaplasic variant. Based on two clinical cases, we examine the place of tyrosin kinase inhibitors in unusual, refractory, situations, i.e. iodine-refractory or metastatic cancer. The ideal medical approach implies a multidisciplinary teamwork.

Real-World Evaluation of Quality of Life, Effectiveness, and Safety of Aflibercept Plus FOLFIRI in Patients with Metastatic Colorectal Cancer: The Prospective QoLiTrap Study.

Aflibercept plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer after the failure of oxaliplatin-containing therapy. QoLiTrap prospectively evaluated the quality of life (QoL) and effectiveness of this regimen in daily clinical practice, according to RAS status, sex, and prior targeted therapy, especially epidermal growth factor receptor inhibitors (EGFR-I). The primary endpoint was the percentage of patients whose EORTC QLQ-C30 global health status (GHS) improved or reduced by <5% from baseline during the first 12 weeks of therapy. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. One thousand two hundred and seventy-seven patients were treated with aflibercept plus FOLFIRI and 872 were evaluable for QoL. GHS improved or decreased by <5% in 40.3% of cases. The ORR was 20.8%, the median PFS was 7.8 months (95% confidence interval (CI), 7.3−8.3), and the median OS was 14.4 months (95% CI, 13.1−18.1). After prior EGFR-I, the ORR was 23.7%, median PFS was 9.4 months (95% CI, 6.5−12.9), and median OS was 17.4 months (95% CI, 10.5−33.7). The safety profile was consistent with previously reported data. Aflibercept plus FOLFIRI given in daily practice maintained QoL in mCRC patients, was associated with a high objective tumor response, and retained its activity regardless of sex, RAS status, and prior EGFR-I therapy.

Patterns of care and economic consequences of using bone-targeted agents for castration-sensitive prostate cancer patients with bone metastases to prevent skeletal-related events in Switzerland - the SAKK 95/16 prostate study.

BACKGROUND: International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland. METHODS: To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-specific antigen (PSA) progression for the extrapolated patient group, using data from NICER. The cost calculation covered costs for bone-targeted agents, their administration and skeletal-related events. The time to PSA progression (33.2 months), as well as the probability and cost of skeletal-related events were derived from the literature. RESULTS: The survey was answered by 86 physicians treating 417 patients, of whom 106 (25.4%) had prostate cancer, with 36 (34.0%) of these mCSPC. The majority of mCSPC patients (52.8%, n = 19) received bone-targeted agents monthly. Denosumab was the treatment of choice in 84.2% of patients (n = 16). Extrapolation using data from NICER indicated that 568 mCSPC patients may be treated with bone-targeted agents at doses used for bone metastasis  every year in Switzerland, leading to estimated total costs of more than CHF 8.3 million over 33.2 months. Because of its more frequent prescription and higher price, it appears that almost 93% of the total costs can be attributed to denosumab. For both denosumab and zoledronic acid, the most expensive components were the cost of administration and the drug cost, making up more than 90% of the total costs, with the rest being costs of skeletal-related events. CONCLUSIONS: This study found that the administration of bone-targeted agents in doses used for bone-metastatic diseases to prevent skeletal-related events is frequent in the setting of mCSPC and results in significant costs for the healthcare system.

Patterns of care for patients with metastatic bone disease in solid tumors: A cross-sectional study from Switzerland (SAKK 95/16).

BACKGROUND: Bone-targeted agents (BTAs) are widely used in the management of patients with bone metastases from solid tumors, but knowledge of their routine care use and the therapeutic implications remains limited. This non-interventional study aimed to characterize real-world BTA patterns of care in Switzerland. MATERIALS AND METHODS: Non-interventional, cross-sectional study involving oncologists from across Switzerland who completed a Treating Physician questionnaire, providing data on their clinical setting and BTA-related practices, and a Patient Characteristics and Treatment questionnaire, providing data on their patients' disease status, risk of bone complications, BTA regimen and related outcomes. Eligible patients were aged ≥ 18 years, with solid tumors and at least one bone metastasis and were receiving routine management at the participating physician's center over the 3-month study period. RESULTS: A total of 86 oncologists recruited 417 patients from across 18 centers in Switzerland (80% public hospitals; 20% private clinics). The majority of physicians (70.9%) reported prescribing BTAs in line with international guidelines; denosumab was the treatment of choice in 78.5% of patients. BTAs were widely administered (94.2%) according to a 3-4-weekly dosing regimen; 33.7% of physicians reported extending intervals to 12 weeks after an initial 2 years of treatment. Physicians appeared to use clinical judgement, as well as formal risk assessment, to guide treatment for symptomatic skeletal events. No association was seen between either BTA use, or risk of complications, and incidence of skeletal complications. Only 4.3% of patients were reported to be experiencing severe bone pain at the time of the study. CONCLUSIONS: This cross-sectional, non-interventional study found high implementation of guideline-recommended BTA prescribing, good pain control and low incidence of skeletal-related events. Long-term BTA randomized controlled trials have the potential to further optimize routine care outcomes for patients.