Patient and General Population Preferences Regarding the Benefits and Harms of Treatment for Metastatic Prostate Cancer: A Discrete Choice Experiment.

Background: Patient preferences for treatment outcomes are important to guide decision-making in clinical practice, but little is known about the preferences of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Objective: To evaluate patient preferences regarding the attributed benefits and harms of systemic treatments for mHSPC and preference heterogeneity between individuals and specific subgroups. Design setting and participants: We conducted an online discrete choice experiment (DCE) preference survey among 77 patients with metastatic prostate cancer (mPC) and 311 men from the general population in Switzerland between November 2021 and August 2022. Outcome measurements and statistical analysis: We evaluated preferences and preference heterogeneity related to survival benefits and treatment-related adverse effects using mixed multinomial logit models and estimated the maximum survival time participants were willing to trade to avert specific adverse effects. We further assessed characteristics associated with different preference patterns via subgroup and latent class analyses. Results and limitations: Patients with mPC showed an overall stronger preference for survival benefits in comparison to men from the general population (p = 0.004), with substantial preference heterogeneity between individuals within the two samples (both p < 0.001). There was no evidence of differences in preferences for men aged 45-65 yr versus ≥65 yr, patients with mPC in different disease stages or with different adverse effect experiences, or general population participants with and without experiences with cancer. Latent class analyses suggested the presence of two groups strongly preferring either survival or the absence of adverse effects, with no specific characteristic clearly associated with belonging to either group. Potential biases due to participant selection, cognitive burden, and hypothetical choice scenarios may limit the study results. Conclusions: Given the relevant heterogeneity in participant preferences regarding the benefits and harms of treatment for mHSPC, patient preferences should be explicitly discussed during decision-making in clinical practice and reflected in clinical practice guidelines and regulatory assessment regarding treatment for mHSPC. Patient summary: We examined the preferences (values and perceptions) of patients and men from the general population regarding the benefits and harms of treatment for metastatic prostate cancer. There were large differences between men in how they balanced the expected survival benefits and potential adverse effects. While some men strongly valued survival, others more strongly valued the absence of adverse effects. Therefore, it is important to discuss patient preferences in clinical practice.

High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08.

BACKGROUND: High rates of venous thromboembolic events (VTEs), mainly in advanced disease, are reported for patients with cancer of the upper gastrointestinal tract (stomach, pancreas) and for treatment with cisplatin. METHODS: Exploratory analysis of VTEs reported as adverse events and serious adverse events in a prospective, randomised, multicentre, multimodal phase III trial according to VTEs reported as adverse events and severe adverse events. Patients with resectable oesophageal cancer (T2N1-3, T3-4aNx) were randomized to 2 cycles of chemotherapy with docetaxel 75 mg/m2, cisplatin 75 mg/m2 followed by chemo-radiotherapy (CRT) and subsequent surgery (control arm) or the same treatment with addition of cetuximab (investigational arm). RESULTS: VTEs occurred in 26 of 300 patients included in the trial, resulting in an incidence rate (IR) of 8.7% [95% CI 5.7-12.4%]. A total of 29 VTEs were reported:13 (45%) VTEs were grade 2, 13 (45%) grade 3 and three (10%) fatal grade 5 events. 72% (21/29) of all VTEs occurred preoperatively (IR 6.7%): 14% (4/29) during chemotherapy and 59% (17/29) during CRT. In multivariable logistic regression only adenocarcinoma (IR 11.1%, 21/189 patients) compared to squamous cell cancer (IR 4.5%, 5/111 patients) was significantly associated with VTE-risk during treatment, OR 2.9 [95%CI 1.0-8.4], p = 0.046. Baseline Khorana risk score was 0 in 73% (19/26), 1-2 in 23% (6/26) and 3 in only 4% (1/26) of patients with VTEs. CONCLUSION: A high incidence of VTEs during preoperative therapy of resectable oesophageal cancer is observed in this analysis, especially in patients with adenocarcinoma. The role of prophylactic anticoagulation during neoadjuvant therapy in resectable esophageal cancer should be further evaluated in prospective clinical trials. According to our data, which are in line with other analysis of VTE-risk in patients with oesophageal cancer patients treated with neoadjuvant cisplatin-based chemotherapy and CRT, prophylactic anticoagluation could be considered balanced against individual bleeding risks, especially in patients with adenocarcinoma. In addition to the established risk factors, oesophageal adenocarcinoma treated with neoadjuvant cisplatin-based therapy may be regarded as a high-risk situation for VTEs. TRIAL REGISTRATION: Registered at clinicaltrials.gov, NCT01107639, on 21 April 2010.

Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: Results of the PANOVA phase 2 study.

BACKGROUND: Tumor Treating Fields (TTFields), low intensity alternating electric fields with antimitotic activity, have demonstrated survival benefit in patients with glioblastoma. This phase 2 PANOVA study was conducted to examine the combination of TTFields plus chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Forty patients with newly-diagnosed, locally advanced or metastatic PDAC received continuous TTFields (150 KHz for ≥18 h/day) plus gemcitabine (1000 mg/m2), or gemcitabine plus nab-paclitaxel (125 mg/m2). The primary endpoint was safety and secondary endpoints included compliance to TTFields, progression-free survival (PFS), and overall survival (OS). RESULTS: Seventeen patients (85%) in each cohort reported Grade ≥3 adverse events (AEs). No increase in serious AEs (SAEs) was observed compared to that anticipated with systemic chemotherapy alone. Twenty-one patients reported TTFields-related skin toxicity, of which 7 were Grade 3; all resolved following temporary reduction of daily TTFields usage. No TTFields-related SAEs were reported. Compliance to TTFields was 68-78% of the recommended average daily use in both cohorts. Median PFS was 8.3 months (95% CI 4.3, 10.3) and median OS was 14.9 months (95% CI 6.2, NA) in the TTFields + gemcitabine cohort. In the TTFields + gemcitabine + nab-paclitaxel cohort, the median PFS was 12.7 months (95% CI 5.4, NA); median OS has not been reached. CONCLUSION: The PANOVA trial demonstrated that the combination of TTFields and systemic chemotherapy is safe and tolerable in patients with advanced PDAC. Based on the safety and preliminary efficacy results of this phase 2 study, a randomized phase 3 study (PANOVA-3) is underway.

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.

Predictors of venous thromboembolic events associated with central venous port insertion in cancer patients.

Insertion of central venous port (CVP) catheter in the cancer population is associated with increased incidence of venous thromboembolic events (VTE). However, trials have shown limited benefit of antithrombotic treatment to prevent catheter-related venous thrombosis. This prospective observational cohort study was designed to assess the incidence of VTE closely related to CVP implantation in patients with cancer and undergoing chemotherapy, and to identify a high risk subgroup of patients. Between February 2006 and December 2011, 1097 consecutive cancer patients with first CVP implantation were included. Catheter-related VTE were defined as deep venous thrombosis in the arm, with or without pulmonary embolism (PE), or isolated PE. The incidence of CVP-associated VTE was 5.9% (IC95 4.4-7.3%) at 3 months, and 11.3% (IC95 9.4-13.2%) at 12 months. The incidence of any VTE was 7.6% (IC95 6.0-9.3%) at 3 months, and 15.3% (IC95 13.1-17.6%) at 12 months. High Khorana risk score and lung cancer were significant predictors of 3 month VTE. In conclusion, this large cohort study of patients with first CVP catheter implantation confirms the high incidence of VTE associated with the CVP implantation and allow identifying high risk patients who may benefit from thromboprophylaxis.