Alternatives for the administration of oral antineoplastics in patients with swallowing difficulties.

Oncology patients often experience swallowing difficulties, which can compromise adherence to treatment and consequently reduce its effectiveness. Improper handling of these hazardous drugs can lead to the risk of inhalation of particles or other exposures endangering the health of the persons involved such as nurses and pharmacists. The aim of this review is to analyse and update the recommendations for the manipulation of oral antineoplastic drugs in patients with swallowing difficulties. A literature review of articles, websites, guidelines and other documents published up to about the conditions of handling and administration of oral antineoplastic agents in oncology and oncohaematology was carried out. A table of 110 active principles was compiled. The information was grouped according to the name of the drug, instructions for oral and nasogastric tube administration and suggested recommendations. Among the drugs reviewed, 66.4% were suitable for dissolution. Although there is a lot of information in the literature, the nonstop development of new oncological drugs requires continuous updating. Therefore, we have collected the most recent data to provide a consultation tool for healthcare professionals and patients with swallowing difficulties.

This review can be used by all types of healthcare professionals, especially nurses, who handle oncological medicinal drugs. In addition, the safest handling methods for the worker have been recommended.

Old Issues and New Perspectives on Endometrial Cancer Therapy: How Molecular Characteristics Are Changing the Therapeutic Pathway.

The Cancer Genome Atlas (TCGA) has radically changed the history of endometrial cancer by outlining a new classification, based on its molecular characteristics. In the field of oncology, we are approaching the new era of molecular biology, particularly regarding endometrial cancer, with the increasing importance of targeted therapy. This paper is a review of phase III randomized controlled trials published in English between January 2019 and December 2023, comparing drugs of interest with standard adjuvant treatment and molecular subtypes in endometrial cancer. The use of immunotherapy alone or in combination with chemotherapy as therapy in patients with recurrent or advanced primary or metastatic endometrial cancer significantly improves the prognosis of these patients. The results show greater efficacy of all proposed treatments for mismatch repair deficiency (dMMR/MSI-H) patients compared to mismatch repair proficiency (pMMR) patients. Progression-free survival (PFS) and overall survival (OS) are better in dMMR patients in all studies analysed. Immunotherapy has the potential to revolutionize the gynaecological cancer treatment landscape, offering a new pathway and new hope for endometrial cancer patients, improving their outcomes in the future. Given the exciting results obtained in dMMR/MSI-H patients, MMR status should be investigated in every patient with advanced endometrial cancer at the time of diagnosis.

A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent species of southeast Asia.

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian sub-continent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent, it extends from the Himalayas to Sikkim, Meghalaya, Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological, microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory, hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study.

PURPOSE: Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. METHODS: In Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. RESULTS: Response rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. CONCLUSIONS: This Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.

Development and psychometric evaluation of the adjuvant endocrine therapy beliefs scale for breast cancer survivors.

PURPOSE: Adjuvant endocrine therapy has a vital role in reducing breast cancer mortality. The beliefs in adjuvant endocrine therapy is a very important factor in the medication adherence of breast cancer survivors. Therefore, it is necessary to develop a standardized scale for assessment of adjuvant endocrine therapy. The purpose of this study was to identify the attributes of adjuvant endocrine therapy beliefs, and to evaluate adjuvant endocrine therapy beliefs scale psychometric properties. METHODS: A hybrid model was applied to identify the concept of adjuvant endocrine therapy beliefs and measurement question were developed by the scale development process. Statistical analysis using validity analysis and Rasch analysis based on item response theory were performed. A total of 228 breast cancer survivors in South Korea participated in the study. RESULTS: The finally developed adjuvant endocrine therapy beliefs scale consisted of 22 items. The items extracted by 4 factors explained 59.72% of the total variance. The model fit showed an acceptable level. The adjuvant endocrine therapy beliefs scale was excellent in convergent and discriminant validity with reliability. CONCLUSION: This scale is expected to be practical and useful in identifying adjuvant endocrine therapy beliefs and developing intervention strategies to promote adjuvant endocrine therapy adherence. In addition, continuous education and support should be accompanied so that breast cancer survivors can maintain positive beliefs in adjuvant endocrine therapy adherence.

Disparities in PI3K/mTOR inhibitor use, toxicities, and outcomes among patients with metastatic breast cancer.

PURPOSE: Novel agents such as PI3K and mTOR inhibitors (PI3K/mTORi) have expanded treatment options in metastatic breast cancer (MBC). Nevertheless, mortality rates remain disproportionately high for Black patients and patients with lower socioeconomic status. Furthermore, clinical trials for these novel agents lacked diversity, so their toxicity profile in minority populations is uncertain. METHODS: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database for patients with HR+, HER2- MBC. Multivariable logistic regression was used to evaluate factors associated with PI3K/mTORi use and toxicity outcomes. RESULTS: A total of 9169 patients with MBC were included in our analysis, of which 1780 (19.4%) received a PI3K/mTORi. We estimated the conditional total effect of insurance through Medicaid, and found lower odds of use of PI3K/mTORi among patients on Medicaid compared to those with commercial insurance (OR 0.73, 95% CI 0.54-0.99, p = 0.049). Odds of PI3K/mTORi use were higher for patients treated at an academic center (OR 1.28, CI 1.06-1.55, p = 0.01). Modeled as a controlled direct effect, Black/African American (Black/AA) race had no impact on odds of PI3K/mTOR use. Black/AA patients had twice the odds of developing hyperglycemia on PI3K/mTORi compared to White patients (OR 2.02, CI 1.24-3.39, p < 0.01). CONCLUSION: This analysis of real-world data suggests that the use of PI3K/mTORi is influenced by socioeconomic factors. We also found racial disparities in toxicity outcomes, with Black/AA patients having twice the risk of hyperglycemia. Our findings call for greater efforts to ensure access to novel treatments and improve their tolerability in diverse populations.

Advancements in steroidal Pt(II) & Pt(IV) derivatives for targeted chemotherapy (2000-2023).

One of the key strategies in chemotherapy involves crosslinking the DNA strands of cancer cells to impede their replication, with platinum (Pt) coordination compounds being a prominent class and cisplatin being its major representative. Steroidal ligands tethered to DNA interactive Pt core act as drug carriers for targeted therapy. While crosslinking of nuclear or mitochondrial DNA strands using coordination complexes has been studied for years, there remains a lack of comprehensive reviews addressing the advancements made in steroidal-Pt derivatives. This review specifically focuses on advancements made in steroid-tethered structural derivatives of Pt(II) or prodrug Pt(IV) for targeted chemotherapy, synthesized between 2000 and 2023. This period was deliberately chosen due to the widespread use of computational techniques for more accurate structure-based drug-design in last two decades. This review discusses the strategy behind tethering steroidal ligands such as testosterone, estrogen, bile acids, and cholesterol to the central DNA interactive Pt core through specific linker groups. The steroidal ligands function as drug delivery vehicles of DNA interactive Pt core and bind with their respective target receptors or proteins that are often overexpressed in cancer cells, thus enabling targeted delivery of Pt moiety to interact with DNA. We discussed structural features such as the location of the linker group on the steroid, the mono, bi, and tridentate configuration of the chelating arm in coordination with Pt, and the rigidity and flexibility of the linker group. The comparative in vitro, in vivo activities, and relative binding affinities of the designed compounds against standard Pt drugs are also discussed. We also provided a critique of observed trends and shortcomings. Our review will provide insights into future molecular designing of targeted DNA crosslinkers and their structural optimization to achieve desired drug properties. From this analysis, we proposed further research directions leading to the future of targeted chemotherapy.

Annexin-A5 Overexpression Increases Sensitivity of MCF-7 and MCF-7/ADR Cells to Epirubicin.

Background: Multi-drug resistance is an important challenge in the chemotherapy of cancer. The role of annexin A5 (ANXA5) in the biology of cancer has been the focus of many studies. Breast Cancer (BC) is frequent cancer in women with high morbidity and mortality rate. The present study aimed to investigate the effects of ANXA5 overexpression on the anti-tumor activity of Epirubicin (EPI) in MCF-7 and MCF-7/ADR cells. Methods: MCF-7 and MCF-7/ADR cells were transfected with the pAdenoVator-CMV-ANXA5-IRES-GFP plasmid or mock plasmid. The overexpression of ANXA5 was evaluated using qPCR. The effects of ANXA5 overexpression and EPI on the cell viability of MCF-7 and MCF-7/ADR cells were measured using an MTT assay. Cell apoptosis was measured by annexin V/7-AAD flow cytometry assay. Results: Following the overexpression of ANXA5, the viability of MCF-7 and MCF-7/ADR was significantly decreased. Furthermore, the overexpression of ANXA5 in MCF-7 cells increased the cytotoxic effects of EPI in all doses and reduced the IC50 of EPI from 17.69 µM to 4.07 µM. Similarly, the overexpression of ANXA5 in MCF7-ADR cells reduced the IC50 of EPI from 27.3 µM to 6.69 µM. ANXA5 overexpression alone or combined with EPI treatment increased the apoptosis of MCF7 and MCF7-ADR cells. Conclusion: The results of the present study demonstrate that ANXA5 overexpression increases the sensitivity of MCF-7 and MCF-7/ADR to EPI, suggesting a possible beneficial role of ANXA5 in the therapy of BC.

Profile of adverse drug reactions reported via the Continuum+ platform: Results from three-year regional follow-up.

In 2017, the Continuum+ platform was launched to provide a monitoring solution to home-based cancer care patients: AKO@dom monitoring. This platform also offers the follow-up of adverse drug reactions (ADRs) via direct notification to regional centers of pharmacovigilance (RCPVs). According to previous studies, the AKO@dom monitoring has successfully maintained treatment at the maximum effective dosage, managing ADRs and patient satisfaction. However, on the pharmacovigilance side, opinions are more divided. Due to the launch of the AKO@dom-PICTO experimentation in December 2021, in which our RCPV takes part, and to provide more data on pharmacovigilance, we decided to conduct a descriptive analysis of cases reported to our RCPV via the Continuum+ platform between 2019 and 2022. During these three years, we analyzed 1070 events, corresponding to 37 patients. Patients were primarily women (74.8%) aged around seventy with breast cancer. The most used drugs were tyrosine kinase inhibitors: palbociclib (29.7%), axitinib (16.2%), and cabozantinib (13.2%). Patients had an average of 8 ADRs, including one serious and/or unexpected ADR. Although the Continuum+ platform makes it possible to considerably limit under-reporting in pharmacovigilance, it has shortcomings. The lack of medical elements and context in notifications is a massive problem for analyzing pharmacovigilance reports. Improved access to the platform's medical information for RCPVs and pharmacovigilance training for healthcare professionals would make Continuum+ a helpful tool in pharmacovigilance.

The real-world data of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study.

BACKGROUND: The real-world efficacy, feasibility, and prognostic factors of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer are not fully established. METHODS: This multi-institutional retrospective cohort study evaluated 71 consecutive patients treated with immune-checkpoint inhibitor combination therapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, safety, and long-term survival. RESULTS: In patients with measurable lesions, the response rate was 58%, and the disease control rate for all enrolled patients was 80%. Five patients (7.0%) underwent successful conversion surgery. Grade 3 or higher immune-related adverse events occurred in 13% of patients, and one patient (1.4%) died due to cholangitis. Median progression-free survival was 9.7 (95% confidence interval: 6.5-not reached). C-reactive protein levels and performance status were identified as significant predictors of progression-free survival through Cox proportional hazards analysis. CONCLUSIONS: Immune-checkpoint inhibitor combination therapy for esophageal cancer demonstrated comparable tumor response, safety, and long-term survival to previous randomized clinical trials. Patients with good performance status and low C-reactive protein levels may be suitable candidates for this treatment.

Fertility preservation counseling for women of reproductive age diagnosed with cancer: an integrative review.

This integrative review synthesizes the scientific evidence on fertility preservation counseling prior to oncological treatment for women of reproductive age diagnosed with cancer. Bibliographic research was conducted on databases PubMed, CINAHL, LILACS, EMBASE, Scopus, and Web of Science. The structured search strategy for the review question was "counseling AND antineoplastic agents AND fertility preservation". The use of controlled descriptors and keywords was adapted for each database. Study selection through the Rayyan platform was independent and blinded. The final sample comprised seven studies emphasizing the importance of clarifying factors related to the risk of infertility due to oncological treatment and fertility preservation techniques, such as success rate, pregnancy rate, cost, available options, and side-effects, as well as discussing the possibilities of adoption and surrogacy. This review provided evidence reinforcing the importance of counseling for fertility preservation, promoting motherhood for women who face oncological treatment. Organized networks linking oncology and reproductive medicine units are crucial to facilitate patient referral between these services and interprofessional communication.

Comparative study of oncology patients' quality of life.

BACKGROUND: A cancer diagnosis has a significant impact on a person's life, both physically and emotionally. However, the oncology patients' QoL (QoL) at different stages of the disease has been under investigated. AIM: To assess and compare the QoL in three groups of oncology patients. METHODS: A comparative study was carried out in an outpatient care service at a public hospital in the state of São Paulo. Data collection involved the use of the Palliative Performance Scale and the McGill QoL Questionnaire. RESULTS: Most participants were women, Catholic and living with a partner. The Palliative Performance Scale revealed a predominance of stable patients (score: ≥70 points). Overall, palliative care patients had lower QoL scores compared to the other groups (p<0.01). CONCLUSION: QoL was worse among palliative care patients. Advanced age, being in palliative care, and have a low-income were negatively associated with a patient's QoL.

Influence of cancer in pregnancy on obstetric and neonatal outcomes: an observational retrospective cohort study.

OBJECTIVE: The study aimed to review the oncological characteristics and treatment of pregnancy-associated cancers and analyze the obstetric and neonatal outcomes to provide evidence-based recommendations for reproductive function preservation, oncological treatment, and obstetric management. METHODS: We conducted an observational retrospective cohort study among pregnant patients with cancer in 7 Chinese tertiary A hospitals from 2003 to 2021. We conducted multiple logistic regression to determine the influence of various factors on preterm birth and small-for-gestational-age infants, log-binomial regression to analyze temporal changes, and χ² tests to explore the effects of cancer type/treatment. RESULTS: Of 204 women, 17% terminated their pregnancies; 59% received pre-delivery treatment. Every 6 years, the rates of pregnancy termination (relative risk [RR]=0.48; 95% confidence interval [CI]=0.35-0.67) and iatrogenic preterm births (RR=0.73; 95% CI=0.54-0.98) reduced, and that of pre-delivery treatment increased, mainly due to increased rates of surgery (RR=1.87; 95% CI=1.31-2.67). Maternal systemic diseases were related to small-for-gestational-age infants (odds ratio [OR]=12.02; 95% CI=1.82-79.43). Chemotherapy with taxanes plus platinum-based agents was related to adverse obstetric outcomes (OR=1.87; 95% CI=1.42-2.46; p<0.05). Thyroid (OR=0.36; 95% CI=0.22-0.57) and ovarian cancer (OR=0.70; 95% CI=0.50-0.98) were associated with fewer cesarean sections. Thyroid cancer was associated with fetal growth restriction (OR=5.21; 95% CI=1.21-22.55). CONCLUSION: Rates of pregnancy termination in cancer declined. Taxane plus platinum-based chemotherapy was associated with adverse obstetric outcomes. Cancer type influenced outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Register Identifier: ChiCTR2100044292.

Extravasation of brentuximab vedotin, an antibody-drug conjugate, in a patient with anaplastic large cell lymphoma.

Brentuximab vedotin (BV) is an antibody-drug conjugate, consisting of a CD30-directed antibody, conjugated by a protease-cleavable linker to a microtubule disrupting agent auristatin E (MMAE). Although the safety datasheet of BV does not warn of severe toxic effects of extravasation, we report a third case of a patient with anaplastic large cell lymphoma who developed severe epidermal necrosis after extravasation. The reason for what happened could be attributed to the fact that MMAE belongs to the group of vinca alkaloids so it should be handled like other tissue-necrotising chemotherapeutics. Reporting of all cases of extravasation involving new conjugated chemotherapeutic drugs is of the utmost importance to be able to develop updated guidelines. Hospital pharmacists can provide information on how to manage extravasation, assess the potential risk, and have a crucial role in drafting hospital protocols.

Evaluating oxidative stress biomarkers in oncology nurses exposed to antineoplastic drugs: A cross-sectional study.

PURPOSE: Antineoplastic drugs (ADs) are widely used in cancer treatment. Nurses in chemotherapy centers are exposed to these drugs during preparation. They can affect healthy cells, leading to teratogenic and mutagenic effects, as well as oxidative stress. This study aimed to evaluate oxidative stress biomarkers in the nurses exposed to these drugs. METHOD: This study was conducted on 30 nurses exposed to ADs and 30 nurses with no exposure to these drugs as non-exposed group. Oxidative stress biomarkers were measured in the blood serum samples of both groups, including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and blood thiol groups. RESULTS: Considering the possibility of confounding effect of nutritional supplement consumption, the effect of this factor was adjusted in the analysis. A significant difference was observed for CAT, SOD, thiol, and TAC biomarkers between two groups (P < 0.05). However, the difference in MDA and GPx biomarkers between two groups was not statistically significant. CONCLUSIONS: The findings of the present study showed that supplement consumption has a significant effect on the biomarker of total antioxidant capacity. Thus, total antioxidant capacity measurement is advised as the best biomarker for tracking oxidative status in nurses exposed to ADs due to its capacity to measure all antioxidants in the body, except the thiol group, and its lower cost when compared to other biomarkers. Furthermore, it can be claimed that the consumption of nutritional supplements has a greater effect on the non-enzymatic biomarkers of oxidative stress than on enzymatic antioxidant system.

Antineoplastic agents associated with neutropenic enterocolitis in patients with malignancy: A quantitative safety signal analysis.

BACKGROUND: The use of certain chemotherapy agents is associated with the development of a condition called "chemotherapy-associated neutropenic enterocolitis" (CANE). OBJECTIVE: To determine the risk of CANE associated with the use of each antineoplastic agent. METHODS: The FDA FAERS database of spontaneous adverse reactions was searched for the occurrence of the MedDRA preferred term "neutropenic colitis." RESULTS: The search resulted in 1134 records of patients (535 [47.3%] females, 479 [42.2%] males, sex not specified in 120 [10.6%]) with neutropenic colitis receiving immunosuppressive chemotherapy. The mean age of patients was 47 (SD 22). 22 antineoplastic agents were found to have a strong association (reported odds ratio [ROR] > 100) with the occurrence of CANE; 9 had ROR < 2. CONCLUSION: Drug databases have several limitations in providing updated information about newly approved pharmaceutical adverse events. Signal detection is a diagnostic method recognized as practical in pharmacovigilance. It may be utilized in the FDA's adverse event reporting database and has demonstrated a reasonable predictive performance in signaling adverse events. Our study emphasized the substantial knowledge gap between what we know about the potential risk of CANE caused by antineoplastic agents and the reports of the FDA on their new approved products.

Commercial Versus Medicaid Insurance and Use of High-Priced Anticancer Treatments.

BACKGROUND: Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs Medicaid) and the use of high-priced cancer treatments. MATERIALS AND METHODS: We linked cancer registry, administrative claims, and demographic data for individuals diagnosed with cancer in North Carolina from 2004 to 2011, with either commercial or Medicaid insurance. We selected cancers with multiple FDA-approved, guideline-recommended chemotherapy options and large price differences between treatment options: advanced colorectal, lung, and head and neck cancer. The outcome was a receipt of a higher-priced option, and the exposure was insurer: commercial versus Medicaid. We estimated risk ratios (RRs) for the association between insurer and higher-priced treatment using log-binomial models with inverse probability of exposure weights. RESULTS: Of 812 patients, 209 (26%) had Medicaid. The unadjusted risk of receiving higher-priced treatment was 36% (215/603) for commercially insured and 27% (57/209) for Medicaid insured (RR: 1.31, 95% CI: 1.02-1.67). After adjustment for confounders the association was attenuated (RR: 1.15, 95% CI: 0.81-1.65). Exploratory subgroup analysis suggested that commercial insurance was associated with increased receipt of higher-priced treatment among patients treated by non-NCI-designated providers (RR: 1.53, 95% CI: 1.14-2.04). CONCLUSIONS: Individuals with Medicaid and commercial insurance received high-priced treatments in similar proportion, after accounting for differences in case mix. However, modification by provider characteristics suggests that insurance type may influence treatment selection for some patient groups. Further work is needed to determine the relationship between insurance status and newer, high-price drugs such as immune-oncology agents.

Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy.

BACKGROUND AND OBJECTIVE: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL). METHODS: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation. We analyzed the QLQ-C30 change from baseline to week 12, the confirmed improvement rate, and the time to improvement or deterioration. KEY FINDINGS AND LIMITATIONS: Baseline PRO compliance rates were 91% for the EV arm (n = 301) and 89% for the chemotherapy arm (n = 307); the corresponding average rates from baseline to week 12 were 70% and 67%. Patients receiving EV versus chemotherapy had reduced pain (difference in change from baseline to week 12: -5.7, 95% confidence interval [CI] -10.8 to -0.7; p = 0.027) and worsening appetite loss (7.3, 95% CI 0.90-13.69; p = 0.026). Larger proportions of patients in the EV arm reported HRQoL improvement from baseline than in the chemotherapy arm; the odds of a confirmed improvement across ten QLQ-C30 function/symptom scales were 1.67 to 2.76 times higher for EV than for chemotherapy. Patients in the EV arm had a shorter time to first confirmed improvement in global health status (GHS)/QoL, fatigue, pain, and physical, role, emotional, and social functioning (all p < 0.05). EV delayed the time to first confirmed deterioration in GHS/QoL (p = 0.027), but worsening appetite loss occurred earlier (p = 0.009) in comparison to chemotherapy. CONCLUSIONS AND CLINICAL IMPLICATIONS: HRQoL with EV was maintained, and deterioration in HRQoL was delayed with EV in comparison to chemotherapy. Better results with EV were reported for some scales, with the greatest difference observed for pain. These findings reinforce the EV safety and efficacy outcomes and benefits observed in EV-301. PATIENT SUMMARY: Patients with previously treated advanced cancer of the urinary tract receiving the drug enfortumab vedotin maintained their HRQoL in comparison to patients treated with chemotherapy. The EV-301 trial is registered on ClinicalTrials.gov as NCT03474107 and on EudraCT as 2017-003344-21.

Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia.

Aim: To characterize real-world patients with metastatic hormone-sensitive prostate cancer (mHSPC) and treating physicians and evaluate treatment trends and baseline concordance versus guidelines internationally. Materials & methods: Retrospective, cross-sectional data from the Ipsos Global Oncology Monitor database 2018-2020 were used for descriptive analysis of mHSPC patients, treating physicians and treatment utilization. Results: Among the 6198 mHSPC patients from five countries, the most common treatment was either androgen deprivation therapy (ADT) monotherapy or first-generation androgen receptor inhibitor + ADT. Second-generation androgen receptor inhibitor use was only initiating but increasing over the study period. Conclusion: Despite contemporaneous guidelines recommending treatment intensification of ADT in combination with novel antihormonals or docetaxel, 76.1% of reported mHSPC patients received non-guideline-concordant care.

Prostate cancer is the second most common cancer among men worldwide and a leading cause of cancer-related death globally. Metastatic hormone-sensitive prostate cancer (mHSPC) refers to the stage of prostate cancer where it has spread to other parts of the body ('metastatic') but still responds to hormonal therapy ('hormone-sensitive'), such as androgen deprivation therapy (ADT). Treatment guidelines around the world for men with mHSPC have changed over time, but there remains a lack of understanding of how well guidelines are followed in real-world practice. Consequently, this study analyzes real-world data from five countries between 2018 and 2020 to understand treatment patterns, baseline concordance versus guidelines and potential drivers of treatment trends. The study found prevalent use of ADT monotherapy and older antihormonal agents, and only marginal but increasing use of novel antihormonals in real-world practice. These practices deviate from guidelines from the study period, which generally recommended ADT combination with either newer antihormonal agents or docetaxel for patients with mHSPC. Overall, the proportion of the 6198 patients treated with non­guideline-concordant therapies was 76.1%. Since guideline-recommended care is associated with better outcomes, this baselining finding highlights the need for appropriate treatment selection and intensification for mHSPC patients.