Identifying the Needs of Health Care Providers in Advanced First-Line Renal Cell Carcinoma: A Mixed-Methods Research.

INTRODUCTION: Systemic treatments for metastatic or unresectable renal cell carcinoma (mRCC) are rapidly evolving. This study aimed at investigating challenges in the care of mRCC to inform future educational interventions for health care providers (HCPs). MATERIALS AND METHODS: The sequential mixed-method design consisted of a qualitative phase (semistructured interviews) followed by a quantitative phase (online surveys). Participants included US-based medical oncologists, nephrologists, physician assistants, nurse practitioners, and registered nurses. Interview transcripts were thematically analyzed. Survey data was descriptively and inferentially analyzed. RESULTS: Forty interviews and 265 surveys were completed. Analysis revealed four challenges in the care of mRCC patients. A challenge in staying current with emerging evidence and treatment recommendations was found with 33% of surveyed HCPs reporting suboptimal skills interpreting published evidence on the efficacy and safety of emerging agents. A challenge weighing patient health and preferences in treatment decisions was found, especially among HCPs with 3 to 10 years of practice (37%) who reported suboptimal skills in assessing patients' tolerance to side effects. Promoting a collaborative care approach to the management of immune-related adverse events was a challenge, specifically related to barriers involving nephrologists (eg, diverging treatment goals). Breakdowns in communication were reported (46% of HCPs), especially in the monitoring of side effects and treatment adherence. CONCLUSION: This study revealed key challenges faced by HCPs when treating and managing patients with mRCC across multiple providers. Future interventions (eg, community of practice) should aim to address the identified gaps and promote a team-based approach to care that strengthens the complementary competencies of HCPs involved.

Seasonal and Diel Communication Periods of Sympatric Pest Limonius Click Beetle Species (Coleoptera: Elateridae) in Western Canada.

In western North America, sympatric Limonius click beetle species produce limoniic acid [(E)-4-ethyloct-4-enoic acid] as a sex pheromone component (L. canus (LeConte), L. californicus (Mannerheim)) or respond to it as a sex attractant (L. infuscatus (Motschulsky)). We tested the hypothesis that these three congeners maintain species-specificity of sexual communication through nonoverlapping seasonal occurrence and/or contrasting diel periodicity of sexual communication. Using capture times of beetles in pheromone-baited traps as a proxy for sexual communication periods, our data show that L. canus and L. californicus have seasonally distinct communication periods. Most L. canus males (>90%) were captured in April and most L. californicus males (>95%) were captured in May/June/July. As almost exclusively L. infuscatus males were captured in two separate 24-hr trapping studies, with data recordings every hour, it remains inconclusive whether the three Limonius congeners communicate at different times of the day. Males of L. infuscatus responded to pheromone lures only during daytime hours and during the warmest period each day. Captures of L. infuscatus overlapping with those of L. canus in April and those of L. californicus in May/June imply the presence of reproductive isolating mechanisms other than seasonal separation of sexual communication periods.

Identification of the Major Sex Pheromone Component of the Click Beetle Agriotes ferrugineipennis.

Synthetic sex pheromone lures are useful tools to monitor and control populations of adult click beetles (Coleoptera: Elateridae). However, sex pheromones for Agriotes click beetle species native to North America have yet to be identified. Here we report the identification and field testing of the sex pheromone of Agriotes ferrugineipennis. Headspace volatiles from female beetles were collected on Porapak Q, and aliquots of Porapak extract were analyzed by gas chromatographic-electroantennographic detection (GC-EAD) and GC-mass spectrometry. 7-Methyloctyl 7-methyloctanoate (7Me7Me) emitted by females was more abundant and elicited much stronger responses from male antennae than the aldehydes octanal and nonanal and the ketone 6,10,14-trimethyl-2-pentadecanone. In a field experiment, captures of A. ferrugineipennis males in traps baited with candidate pheromone components exceeded those of unbaited control traps, on average by nearly 1,200 times. Neither the ketone nor the aldehydes as lure constituents appeared to alter captures of males in 7Me7Me-baited traps. We conclude that 7Me7Me is the major, and possibly the only, sex attractant pheromone component of female A. ferrugineipennis.

Efficacy of enfortumab vedotin in advanced urothelial cancer: Analysis from the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study.

BACKGROUND: Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials. METHODS: UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were abstracted from chart reviews by investigators at each site. The observed response rate (ORR) was investigator-assessed for patients with at least 1 post-baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy. RESULTS: The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was >40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression-free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06). CONCLUSIONS: In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate < 30 mL/min and significant comorbidities. LAY SUMMARY: Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer. This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations. Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real-world setting, and support the use of this drug in broader patient populations.

Limoniic Acid and Its Analog as Trap Lures for Pest Limonius Species (Coleoptera: Elateridae) in North America.

Four species of Limonius wireworms (Coleoptera: Elateridae), L. californicus, L. canus, L. infuscatus and L. agonus, are serious crop pests in North America. Limoniic acid, (E)-4-ethyloct-4-enoic acid, has been reported as a sex pheromone component of female L. californicus and L. canus, and a sex attractant for male L. infuscatus. In the same study, both limoniic acid and the analog (E)-5-ethyloct-4-enoic acid were highly attractive in field experiments. Moreover, six carboxylic acids in headspace volatiles of Limonius females elicited responses from male antennae but were not tested for behavioral activity. Here, we report trap catch data of Limonius spp. obtained in field experiments at 27 sites across North America. All four Limonius species were attracted to limoniic acid and to the analog but not to the carboxylic acids. Adding these carboxylic acids to limoniic acid, or to the analog, reduced its attractiveness. In dose-response studies, trap lures containing 0.4 mg or 4 mg of limoniic acid afforded large captures of L. californicus and L. infuscatus. Neither limoniic acid nor the analog were deterrent to other elaterid pest species. The broad attractiveness of limoniic acid to Limonius spp., and its non-deterrent effect on heterogeners, may facilitate the development of generic pheromone-based monitoring and management tools for multiple click beetle species.

Ginseng for the Management of Cancer-Related Fatigue: An Integrative Review.

BACKGROUND: Cancer-related fatigue (CRF) is one of the most prevalent, debilitating symptoms affecting a majority of patients with cancer worldwide. It can lead to poor compliance with anticancer therapy and discontinuation of treatment. Current management strategies for CRF center around activity and exercise; however, these strategies can be challenging for many patients undergoing active treatment. Ginseng has been shown to improve CRF and may provide benefit for patients suffering from CRF. METHODS: A systematic review was completed by searching PubMed and Scopus databases. RESULTS: 115 search results were reduced to a final sample of five articles after applying inclusion and exclusion criteria. Published results suggest that 2,000 mg of American ginseng once daily improves symptoms of CRF. Minimal side effects or drug interactions are observed. Additional research is needed to further evaluate the role of ginseng for CRF. CONCLUSION: There are data to support the use of American ginseng to treat CRF. Large-scale randomized controlled trials are needed to validate these findings and determine optimal dosage and duration of therapy.

Limoniic Acid - Major Component of the Sex Pheromones of the Click Beetles Limonius canus and L. californicus.

Wireworms, the larvae of click beetles (Coleoptera: Elateridae), are soil-dwelling insect pests inflicting major economic damage on many types of agricultural crops worldwide. The objective of this work was to identify the female-produced sex pheromones of the Pacific Coast wireworm, Limonius canus LeConte, and the sugarbeet wireworm, L. californicus (Mannerheim) (Coleoptera: Elateridae). Headspace volatiles from separate groups of female L. canus and L. californicus were collected on Porapak Q and analyzed by gas chromatography with electroantennographic detection (GC-EAD) and GC-mass spectrometry. GC-EAD recordings revealed strong responses from male L. canus and male L. californicus antennae to the same compound, which appeared below GC detection threshold. The structure of this candidate pheromone component was deduced from the results of micro-analytical treatments of extracts, retention index calculations on four GC columns, and by syntheses of more than 25 model compounds which were assessed for their GC retention characteristics and electrophysiological activity. The EAD-active compound was identified as (E)-4-ethyloct-4-enoic acid, which we name limoniic acid. In field experiments in British Columbia and Alberta, Canada, traps baited with synthetic limoniic acid captured large numbers of male Limonius click beetles, whereas unbaited control traps captured few. Compared to traps baited with the analogue, (E)-5-ethyloct-4-enoic acid, traps baited with limoniic acid captured 9-times more male L. californicus, and 6.5-times more male western field wireworms, L. infuscatus Motschulsky, but 2.3-times fewer male L. canus. Limoniic acid can now be developed for detection, monitoring and possibly control of L. californicus, L. infuscatus and L. canus populations.

The Role of Metastasectomy in Urothelial Carcinoma: Where Are We in 2020?

Systemic therapy is the mainstay of treatment for metastatic urothelial carcinoma (UC). Responses to first-line platinum-based therapy tend to be short-lived with potential toxicity. Despite the approval of checkpoint inhibitors, the long-term prognosis for patients with metastatic UC remains dismal. Herein we report the case of a patient with a solitary pulmonary metastatic lesion of urothelial origin as the only site of metastatic disease who remained free of disease for more than 2 years without systemic therapy after metastasectomy. We review the literature discussing the role of combined surgical and medical management of oligometastatic UC. As our case illustrates, a growing body of evidence suggests a potential role for a multimodal approach in patients with oligometastatic UC.

Current and Future Landscape of Immune Checkpoint Inhibitors in Urothelial Cancer.

Immune checkpoint inhibitors have revolutionized the field of oncology, providing a novel mechanism for anticancer therapy. Programmed death 1-targeting antibodies pembrolizumab and nivolumab and programmed death ligand 1 (PD-L1)-targeting antibodies atezolizumab, durvalumab, and avelumab have been approved for use in advanced urothelial cancer in the post-platinum setting or in the upfront setting in platinum-ineligible patients. While this represents a significant step forward in management of urothelial cancers, most patients do not have an objective response to these therapies. PD-L1 expression is not a consistently predictive biomarker, but is recommended for checkpoint utilization in select circumstances. We report here a summary of known data and the differences between these agents, as well as future avenues to explore with immuno-oncologic agents in urothelial cancer. Much work is ongoing to better understand resistance mechanisms, to maximize efficacy with combination strategies, to find improved predictive biomarkers, to assess curative-intent strategies, and to better manage toxicity with these agents.

Real-World Experience With Cabozantinib in Metastatic Clear Cell Renal Cell Carcinoma: A Retrospective Analysis.

Cabozantinib inhibits tyrosine kinase activity at the MET, AXL, and VEGF receptors and is approved for front-line therapy in metastatic clear cell renal cell carcinoma. Little off-protocol data exist on tolerability and response. The objective of this retrospective study was to assess off-protocol tolerability and response rates in patients with metastatic clear cell renal cell carcinoma being treated with cabozantinib. Data on baseline disease characteristics and treatment details were retrospectively gathered for patients with metastatic clear cell renal cell carcinoma treated with cabozantinib at The University of Texas MD Anderson Cancer Center from 2015 to 2017. A blinded radiologist determined the best response according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Descriptive statistics were utilized. Cabozantinib has a high disease control rate (92%), even as a late line of therapy in metastatic clear cell renal cell carcinoma. However, careful monitoring is warranted, as many patients require treatment breaks and dose reductions for therapy-related toxicity.

Cabozantinib for the treatment of patients with metastatic non-clear cell renal cell carcinoma: A retrospective analysis.

BACKGROUND: Cabozantinib prolongs overall survival (OS) and progression-free survival (PFS) in patients with metastatic clear cell renal cell carcinoma (RCC) that progressed on first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI). The role of cabozantinib has not been established in non-clear cell renal cell carcinoma (nccRCC). METHODS: This is a retrospective study of 30 patients with nccRCC who received cabozantinib from January 2013 to January 2017. Information collected included baseline characteristics, toxicity, dose reductions, PFS and OS. A fellowship trained abdominal radiologist, blinded to patient history and clinical data, assessed radiographic response using RECIST, v1.1. RESULTS: With a median follow-up of 20.6 months (95% confidence interval [CI]: 11.4-28.8), median PFS was 8.6 months (95% CI: 6.1-14.7), and median OS was 25.4 months (95% CI: 15.5-35.4). Of the 28 patients with measurable disease, 4 had partial responses (2 papillary, 1 chromophobe and 1 unclassified RCC), 18 had stable disease (64.2%) and 6 had progressive disease (21.4%), resulting in a 14.3% objective response rate and a 78.6% disease control rate. Two patients with papillary RCC who had experienced disease progression on savolitinib achieved durable partial response and stable disease, respectively, following treatment with cabozantinib. Of the 21 patients who started cabozantinib at 60 mg/d, 12 (57.1%) required dose reduction due to toxicity. CONCLUSION: In this retrospective study, cabozantinib produced a clinically meaningful benefit in patients with metastatic nccRCC, the majority of whom had disease progression on prior VEGFR-TKIs. Prospective trials of cabozantinib in nccRCC are warranted.

Management of Advanced Bladder Cancer: An Update.

Bladder cancer is the sixth most common cancer in the United States; therefore, the majority of clinicians working in the oncology setting will care for this patient population. Unfortunately, treatment plans, especially in the advanced setting, lack consistency. This, along with the advanced age and comorbidities of most bladder cancer patients, can provide challenges for clinicians when developing treatment plans. In the past 2 years, new drug approvals, specifically those for immune checkpoint inhibitors, have changed the treatment landscape for bladder cancer for the first time since the 1980s. This review article outlines the current management for muscle-invasive and metastatic bladder cancer, while also highlighting future considerations in this disease space. It is imperative that oncology advanced practice providers are up to date with these new changes and have a sound understanding of treatment principles for patients with advanced bladder cancer in order to deliver the safest and most effective care.

Vaginal Testosterone for Management of Aromatase Inhibitor-Related Sexual Dysfunction: An Integrative Review.

PROBLEM IDENTIFICATION: Women taking aromatase inhibitors (AIs) as part of the management of hormone receptor-positive breast cancer experience more symptoms of sexual dysfunction, including vaginal atrophy, as opposed to postmenopausal women and women treated with tamoxifen (Nolvadex®). Vaginal testosterone could be an alternative to estrogen, which is contraindicated in this population.
. LITERATURE SEARCH: A systematic review was completed by searching PubMed and Scopus databases.
. DATA EVALUATION: 64 search results were reduced to a final sample of 3 articles after applying inclusion and exclusion criteria.
. SYNTHESIS: Published results suggest that vaginally applied testosterone doses of 150 mcg and 300 mcg improve symptoms of sexual dysfunction in women taking AIs. Minimal side effects are observed, and estradiol levels are not affected by vaginally applied testosterone. Additional research is needed to evaluate vaginal testosterone in women taking AIs.
. CONCLUSIONS: Vaginal testosterone shows preliminary promise as an option to manage sexual side effects of AI therapy in postmenopausal cancer survivors; however, available data are too limited to draw practice-changing conclusions.
. IMPLICATIONS FOR RESEARCH: Large-scale randomized, controlled trials need to be completed to evaluate the efficacy and safety of vaginal testosterone in women taking AIs.