Real-world clinical outcomes of patients with metastatic renal cell carcinoma receiving pembrolizumab + axitinib vs. ipilimumab + nivolumab.

BACKGROUND: Immune-Oncology (IO) therapies have changed first-line (1L) treatment paradigm for metastatic renal cell carcinoma (mRCC) in last few years with robust clinical trial data. We examined clinical outcomes among clear cell mRCC (mccRCC) patients who received pembrolizumab + axitinib (pembro-axi) or ipilimumab + nivolumab (ipi-nivo) in the US community oncology setting. METHODS: This retrospective cohort study utilized data from electronic health records and chart review within The US Oncology Network to identify adult patients with mccRCC initiating 1L pembro-axi or ipi-nivo from January 01, 2019 to December 31, 2020 and followed through March 31, 2021. Physician-recorded response (real-world overall response rate [rwORR] and real-world disease control rate [rwDCR]) was assessed descriptively. Real-world progression-free survival (rwPFS), real-world time to next treatment (rwTTNT) and time on treatment (rwToT) were estimated using Kaplan-Meier analysis. Association of 1L systemic treatment with time-to-event outcomes was examined using multivariable cox proportional hazards models. RESULTS: Study included 331 mccRCC patients (pembro-axi:44%, ipi-nivo:56%). Median age was 65 years, 75.5% were male, and 82.5% had intermediate/poor (I/P) IMDC risk score. RwORR and rwDCR were 71.0% and 80.0% for pembro-axi and 45.2% and 58.6% for ipi-nivo. In multivariable analysis, pembro-axi was associated with longer rwToT (aHR, 0.53 [95% CI, 0.40, 0.71]), rwTTNT (aHR, 0.60 [95% CI, 0.42, 0.87]), and rwPFS (aHR, 0.70 [95% CI, 0.49, 0.99]) compared to ipi-nivo (P < 0.01). CONCLUSIONS: Our study provides insight into newer mccRCC treatment tolerability and effectiveness in the real-world US community setting. Our real-world results were comparable to data from clinical trials, which is encouraging for mccRCC patients.

Real-world Treatment Patterns and Clinical Outcomes for Metastatic Renal Cell Carcinoma in the Current Treatment Era.

Background: Immuno-oncology (IO) agents and tyrosine kinase inhibitors (TKIs) have revolutionized the treatment paradigm for metastatic renal cell carcinoma (mRCC). Data on real-world usage and outcomes are limited. Objective: To examine real-world treatment patterns and clinical outcomes for mRCC. Design setting and participants: This retrospective cohort study included 1538 patients with mRCC who received first-line treatment with pembrolizumab + axitinib (P + A; n = 279, 18%), ipilimumab + nivolumab (I + N; n = 618, 40%), or TKI monotherapy (TKIm; cabozantinib, sunitinib, pazopanib, or axitinib; n = 641, 42%) between January 1, 2018 and September 30, 2020 in US Oncology Network/non-network practices. Outcome measurements and statistical analysis: The relationship with outcomes, time on treatment (ToT), time to next treatment (TTNT), and overall survival (OS) was analyzed using multivariable Cox proportional-hazards models. Results and limitations: The median age of the cohort was 67 yr (interquartile range 59.5-74.4), 70% were male, 79% had clear cell RCC, and 87% had an intermediate or poor International mRCC Database Consortium risk score. The median ToT was 13.6 for P + A versus 5.8 for I + N versus 3.4 mo for TKIm (p < 0.001) and the median TTNT was 16.4 for P + A versus 8.3 for I + N versus 8.4 mo for TKIm (p < 0.001) . Median OS was not reached for P + A, 27.6 mo for I + N, and 26.9 mo for TKIm (p = 0.237). On adjusted multivariable analysis, treatment with P + A was associated with better ToT (adjusted hazard ratio [aHR] 0.59, 95% confidence interval [CI] 0.47-0.72 vs I + N; 0.37, 95% CI, 0.30-0.45 vs TKIm; p < 0.0001) and better TTNT (aHR 0.61, 95% CI 0.49-0.77 vs I + N; 0.53, 95% CI 0.42-0.67 vs TKIm; p < 0.0001). Limitations include the retrospective design and the limited follow-up for characterization of survival. Conclusions: We noted substantial uptake of IO-based therapies in the first-line community oncology setting since their approval. In addition, the study provides insights into clinical effectiveness, tolerability, and/or compliance of IO-based therapies. Patient summary: We examined the use of immunotherapy for patients with metastatic kidney cancer. The findings suggest rapid implementation of these new treatments by oncologists working in the community setting, which is reassuring for patients with this disease.

Potential of lignocellulose degrading microorganisms for agricultural residue decomposition in soil: A review.

Lignocellulosic crop residues (LCCRs) hold a significant share of the terrestrial biomass, estimated at 5 billion Mg per annum globally. A massive amount of these LCCRs are burnt in many countries resulting in immense environmental pollution; hence, its proper disposal in a cost-effective and eco-friendly manner is a significant challenge. Among the different options for management of LCCRs, the use of lignocellulose degrading microorganisms (LCDMOs), like fungi and bacteria, has emerged as an eco-friendly and effective way for its on-site disposal. LCDMOs achieve degradation through various mechanisms, including multiple supportive enzymes, causing oxidative attacks by which recalcitrance of lignocellulose material is reduced, paving the way to further activity by depolymerizing enzymes. This improves the physical properties of soil, recycles plant nutrients, promotes plant growth and thus helps improve productivity. Rapid and proper microbial degradation may be achieved through the correct combination of the LCDMOs, supplementing nutrients and controlling different factors affecting microbial activity in the field. The review is a critical discussion of previous studies revealing the potential of individuals or a set of LCDMOs, factors controlling the rate of degradation and the key researchable areas for better understanding of the role of these decomposers for future use.

Benefit-risk trade-offs in treatment choice in advanced HER2 negative breast cancer: patient and oncologist perspectives.

Aim: To evaluate which treatment attributes US patients and oncologists prioritize in HER2 negative advanced breast cancer (ABC). Methods: Preferences were assessed via a discrete choice experiment. Also, treatment goal statements were rated on an agreement scale. Results: Patients (n = 169) most valued improving overall survival (OS), followed by improving nausea and neuropathy. Oncologists (n = 117) most valued improving OS, followed by neuropathy and progression-free survival. Regarding treatment goals, oncologists (67%) perceived that patients are more focused on efficacy than quality of life; fewer patients (29%) agreed with this statement; 81% of oncologists and 51% of patients agreed that patients prefer oral treatment. Conclusion: Patients and oncologists were willing to accept increases in toxicities in exchange for efficacy improvements in HER2 negative ABC.

The goal of this study was to understand the preferences of patients and physicians for the benefits and risks associated with the treatment of advanced breast cancer that expresses normal amounts of the HER2 protein (termed as HER2 negative). Respondents completed an exercise where they compared two treatment options at a time that varied in their level of effectiveness and their potential for certain side effects and then selected the treatment option they most preferred. From this exercise, the treatment features that matter the most to patients and physicians were discovered. The most important treatment features for patients were lengthening life expectancy, decreasing the chance of experiencing nausea affecting appetite, and decreasing the chance of experiencing nerve damage involving numbness and/or pain, possibly severe, in hands and feet which may limit daily activities. The most important treatment features for physicians were lengthening life expectancy, decreasing the change of experiencing nerve damage involving numbness and/or pain, possibly severe, in hands and feet which may limit daily activities, and lengthening the time that cancer remains stable and does not worsen. Patients and physicians also rated how much they agreed with statements about their goals for treatment. While 67% of oncologists believed that their patients are more focused on killing the cancer than their quality of life, only 27% of patients were more focused on killing the cancer than their quality of life.

A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status.

INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.

Guar gum based hydrogel as controlled micronutrient delivery system: Mechanism and kinetics of boron release for agricultural applications.

A boron loaded super-absorbent hydrogel (BLSAH) was developed through in situ incorporation of boron (B) in a guar gum-based hydrogel and characterized with FTIR, thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), and swelling studies, showing maximum absorption up to 356 g/g. The release pattern of B from the BLSAH and its kinetics was studied in water as well as soil. The B release pattern of the BLSAH was also compared with the commercial B fertilizer, boronated single super phosphate (bSSP). The BLSAH, following the Fickian mechanism, released 38% B, as compared with 51% of the bSSP, during the incubation period of 30 days in soil. The half-life period for the BLSAH (96.25 days) in soil was almost triple that of the bSSP's half-life (33.32 days), which is indicative of the slow and controlled release of B from the BLSAH. Thus, owing to its sustained nutrient release ability, the synthesized BLSAH exhibited wide potential for applications in agriculture sector.

Patient and oncologist preferences for attributes of treatments in advanced melanoma: a discrete choice experiment.

PURPOSE: To examine and compare patient and oncologist preferences for advanced melanoma treatment attributes and to document their trade-offs for benefits with risks. MATERIALS AND METHODS: A discrete choice experiment (DCE) was conducted among advanced melanoma patients and oncologists. Qualitative pilot testing was used to inform the DCE design. A series of scenarios asked stakeholders to choose between two hypothetical medications, each with seven attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (MDT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3-4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to determine patients' and oncologists' choice-based preferences, analysis of variance models were used to estimate the relative importance of attributes, and independent t-tests were used to compare relative importance estimates between stakeholders. RESULTS: In total, 200 patients and 226 oncologists completed the study. OS was most important to patients (33%), followed by AEs (29%) and ORR (25%). For oncologists, AEs were most important (49%), followed by OS (34%) and ORR (12%). An improvement from 55% to 75% in 1-year OS was valued similar in magnitude to a 23% decrease (from 55% to 32%) in likelihood of AEs for oncologists. CONCLUSION: Patients valued OS, AEs, and ORR sequentially as the most important attributes in making a treatment decision, whereas oncologists valued AEs most, followed by OS and ORR. In comparison, patients differed significantly from oncologists on the importance of ORR, AEs, and PFS, but were consistent in OS and the rest of attributes.

Health Care Resource Utilization and Associated Costs Among Metastatic Cutaneous Melanoma Patients Treated with Ipilimumab (INTUITION Study).

BACKGROUND: There are limited real-world data on health care resource utilization (HCRU) among advanced melanoma patients. The objective of this study was to describe HCRU and health care costs associated with the management of advanced melanoma patients receiving ipilimumab. METHODS: This retrospective multinational, observational study included advanced melanoma patients from Australia, Germany, Italy, and Spain who had received at least 1 dose of ipilimumab. Data extracted from medical charts included inpatient admissions, outpatient visits, surgical procedures, laboratory investigations, radiation therapy, imaging studies, and concomitant medications. Cost estimates were based on unit costs from country-specific standard reimbursement sources. Subgroup analyses were performed for BRAF mutation status and ipilimumab refractory patients, who had disease progression within 24 weeks of their last dose of ipilimumab. RESULTS: Mean age of 362 enrolled patients was 60.6 years (standard deviation [SD] 14.4). During a median follow-up period of 30.2 weeks, 57% of patients were admitted to hospital and 16% underwent surgery. Health care resource utilization rates varied substantially across countries and were highest in Germany. Concomitant medications to treat adverse events were commonly used. Subgroup analyses showed higher utilization rates among ipilimumab refractory and BRAF mutant patients. Mean weekly total costs associated with HCRU were lower in the pre-progression period (€107; 95% confidence interval (CI): 79-145) than in the post-progression period (€216; 95% CI: 180-259). CONCLUSION: Health care resource utilization pattern and associated costs among patients treated with ipilimumab varied greatly among countries and between pre- and post-progression periods. There is a high economic burden associated with ipilimumab refractory melanoma. IMPLICATIONS FOR PRACTICE: Metastatic melanoma patients treated with the anti-CTLA-4 inhibitor ipilimumab have a high utilization of various types of health care services, such as inpatient hospital stays or doctor visits. There are differences across countries regarding patterns of health care utilization and economic burden of the disease. Health care services are used more frequently after patients experience progression of their disease. The study highlights that better therapies leading to durable response in patients with metastatic melanoma have the potential to decrease health care costs and patient burden in terms of hospitalizations and other health care services.

Biopsy Procedures and Molecular Testing Utilization and Related Costs in Patients with Metastatic Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements are key therapeutic targets for biomarker-driven treatment with an EGFR or ALK tyrosine kinase inhibitor (TKI) in patients with metastatic non-small cell lung cancer (NSCLC). To appropriately guide treatment decisions, since 2011, the National Comprehensive Cancer Network and the American Society of Clinical Oncology therefore recommend EGFR and ALK analysis in tumor samples obtained at the time of diagnosis in patients with non-squamous NSCLC. Currently, there are limited data on utilization patterns and cost of biopsy procedures and biomarker tests in patients with metastatic NSCLC who receive an EGFR or ALK TKI. OBJECTIVES: To (a) describe utilization patterns and costs associated with biopsy procedures and biomarker testing in patients with NSCLC who received erlotinib or crizotinib between 2009 and 2012 and (b) investigate the timing of these procedures relative to the erlotinib or crizotinib index date. METHODS: Adult patients with metastatic lung cancer were identified by ICD-9-CM diagnostic codes within the Truven Health Analytic MarketScan database. Patients were included in the analysis if they had an index erlotinib or crizotinib claim between January 1, 2009, and September 30, 2012 (index period) and were continuously enrolled for ≥ 12 months before the index claim. Because there is no specific ICD-9-CM diagnostic code for NSCLC, patients with metastatic lung cancer who received erlotinib or crizotinib were considered to have metastatic NSCLC. Using CPT and ICD-9-CM codes, lung biopsy procedures performed during the 24 months before or 12 months after the index claim date were identified. For every patient, biomarker testing claims for EGFR and ALK were identified using the molecular pathology stacked CPT code during the 2 months before or 1 month after the index date. The frequency of claims for biopsy procedures and biomarker testing was analyzed descriptively. The overall summary measures for biomarker testing, especially frequency of EGFR testing in patients receiving erlotinib, was also described as before and after 2011, the year when biomarker testing became part of the guidelines. Per patient and overall costs for biopsy procedures and biomarker testing were calculated from payer and patient perspectives. RESULTS: Of the 4,926 identified patients, 4,801 (97.5%) received erlotinib, and 125 (2.5%) received crizotinib. Biopsy procedure claims were identified for 3,579 (72.7%) patients, including 3,503 (73.0%) erlotinib recipients and 76 (60.8%) crizotinib recipients. Biomarker testing claims were identified for 675 (13.7%) patients, including 634 (13.2%) erlotinib recipients and 41 (32.8%) crizotinib recipients. Overall, most biomarker testing procedures (476 of 741) were identified in 435 (of 675) patients after year 2011. Also, among erlotinib recipients, percentage of patients receiving EGFR testing was increased over the index period. Per patient mean (SD) numbers of biopsy procedures and biomarker tests were 1.2 (1.1) and 0.2 (0.4), respectively. In the outpatient setting, per patient mean (SD) cost per biopsy procedure was $1,223 ($1,899) from the payer perspective and $60 ($147) from the patient perspective, whereas in the inpatient setting, it was $8,163 ($18,712) and $180 ($691), respectively. Among patients receiving at least 1 biomarker test, the per patient mean (SD) cost for the overall population was $891 ($1,062) and $43 ($229); for erlotinib recipients, it was $906 ($1,084) and $42 ($228); and for crizotinib recipients, it was $664 ($576) and $55 ($243) in payer and patient perspectives, respectively. CONCLUSIONS: This study provides insight into the use and cost of biopsy and biomarker testing procedures in patients with metastatic NSCLC. The low frequency of biomarker testing highlights the need for more awareness of testing to guide treatment decisions in these patients. Costs associated with biopsy procedures and biomarker testing provide insight into the economic impact on metastatic NSCLC patients treated with targeted therapy. DISCLOSURES: This study was sponsored by Merck & Co. Shinde is a study manager working for Merck under contract with AllSourcePPS, an Agile 1 company in Huntington Beach, California. Cao and Kothari are employees of Merck & Co., Kenilworth, New Jersey. Study concept and design were contributed primarily by Shinde and Kothari. Data analysis was performed by Cao. Data interpretation was performed by Shinde, Cao, and Kothari. Shinde wrote the manuscript with assistance from Cao and Kothari. The revision was completed primarily by Shinde and Kothari.