Achieving white blood cell equity: are the safety profiles of biosimilar and reference pegfilgrastims comparable?

Biosimilars can provide choices for patients and may provide cost savings; however, their uptake has been slow in the USA, in part due to limited knowledge. To provide additional confidence in US pegfilgrastim biosimilars, this narrative review compared the safety profiles of biosimilar pegfilgrastims, currently approved or filed for approval in the USA, with the EU- and US-approved reference pegfilgrastims. Headache and bone pain were common to biosimilars and reference products and occurred at a similar incidence. Clinical trial data on the safety profiles of biosimilar pegfilgrastims and reference products have demonstrated similarity and comparability, with no unexpected safety outcomes. Overall, the safety profiles of biosimilar pegfilgrastims and reference pegfilgrastims demonstrated a high degree of similarity and comparability.

Pegfilgrastim is a biologic drug (one made in living cells such as bacteria) that is given to some patients being treated for cancer. Pegfilgrastim is prescribed to reduce a patient's risk of infection due to a weakened immune system caused by various chemotherapy treatment plans. A biosimilar is a type of biologic medicine that is highly similar to a US FDA-approved reference biologic, and is often cheaper, making it more widely available to patients. As of March 2023, there are eight pegfilgrastim biosimilars (six approved and two awaiting approval by the FDA). This review compared the side effects for the reference pegfilgrastim with the biosimilar pegfilgrastims. The side effects in general and the side effects from treatment were similar for the reference pegfilgrastim and for the biosimilar pegfilgrastims, with the most common side effects being headache and bone pain. Serious side effects such as allergic reactions or problems with the spleen were very low and were also similar between the reference pegfilgrastim and the biosimilar pegfilgrastims. These results show that the safety of the biosimilar pegfilgrastims was similar to the reference pegfilgrastim, with no unexpected side effects. With comparable safety to their reference product, biosimilars have the potential to improve patient access to more affordable treatment options.

Soft Tissue Mass Extramedullary Plasmacytoma Following Radiation Therapy for Solitary Bone Plasmacytoma.

Soft tissue involvement in extramedullary plasmacytoma (EMP) is an exceptionally rare occurrence within the spectrum of plasma cell neoplasms. This case report presents the unique scenario of a patient who developed a soft tissue mass EMP subsequent to receiving radiation therapy for a solitary bone plasmacytoma at a distinct anatomical site. The primary objective of this report is to elucidate the clinical characteristics, diagnostic complexities, and management considerations associated with this uncommon presentation. Through a comprehensive review of existing literature, we aim to provide valuable insights and expertise to healthcare providers involved in the assessment and treatment of similar cases.

Exceedingly Rare Bilateral Synchronous Germ Cell Testicular Tumors With Different Histopathological Features.

Bilateral synchronous testicular tumors are a relatively uncommon occurrence, especially when they involve germ cell tumors of different histology. In this context, we present a compelling case report of a male patient who was diagnosed with bilateral synchronous germ cell testicular tumors, with one being a seminoma and the other a non-seminomatous germ cell tumor (NSGCT). The coexistence of two distinct histological types, seminoma and NSGCT, necessitates a comprehensive diagnostic approach to accurately identify and characterize each tumor. This underscores the importance of clinical history, physical examination, imaging techniques, and histopathological analysis to establish an appropriate diagnosis. Careful consideration must be given to factors such as tumor stage, histological subtype, and individual patient characteristics to determine the most suitable treatment strategy. Treatment options may encompass a combination of surgery, chemotherapy, and radiation therapy, tailored to each tumor's specific characteristics and the patient's overall health. By highlighting this unique case, we aim to underscore the significance of meticulous evaluation and accurate diagnosis when confronted with bilateral synchronous testicular tumors of different histology.

Biosimilar Use Among 38 ASCO PracticeNET Practices, 2019-2021.

PURPOSE: Biosimilars offer increased patient choice and potential cost-savings, compared with originator biologics. We studied 3 years of prescribed biologics among US physician practices to determine the relationship of practice type and payment source to oncology biosimilar use. METHODS: We acquired biologic utilization data from 38 practices participating in PracticeNET. We focused on six biologics (bevacizumab, epoetin alfa, filgrastim, pegfilgrastim, rituximab, and trastuzumab) for the period from 2019 to 2021. We complemented our quantitative analysis with a survey of PracticeNET participants (prescribers and practice leaders) to reveal potential motivators and barriers to biosimilar use. We implemented logistic regression to evaluate the biosimilar use for each biologic, with covariates including time, practice type, and payment source, and accounted for clusters of practices. RESULTS: Use of biosimilars increased over the 3-year period, reaching between 51% and 80% of administered doses by the fourth quarter of 2021, depending on the biologic. Biosimilar use varied by practice, with independent physician practices having higher use of biosimilars for epoetin alfa, filgrastim, rituximab, and trastuzumab. Compared with commercial health plans, Medicaid plans had lower biosimilar use for four biologics; traditional Medicare had lower use for five biologics. The average cost per dose decreased between 24% and 41%, dependent on the biologic. CONCLUSION: Biosimilars have, through increased use, lowered the average cost per dose of the studied biologics. Biosimilar use differed by originator biologic, practice type, and payment source. There remains further opportunity for increases in biosimilar use among certain practices and payers.

Reducing Avoidable Emergency Visits and Hospitalizations With Patient Risk-Based Prescriptive Analytics: A Quality Improvement Project at an Oncology Care Model Practice.

PURPOSE: Cancer-related emergency department (ED) visits and hospitalizations that would have been appropriately managed in the outpatient setting are avoidable and detrimental to patients and health systems. This quality improvement (QI) project aimed to leverage patient risk-based prescriptive analytics at a community oncology practice to reduce avoidable acute care use (ACU). METHODS: Using the Plan-Do-Study-Act (PDSA) methodology, we implemented the Jvion Care Optimization and Recommendation Enhancement augmented intelligence (AI) tool at an Oncology Care Model (OCM) practice, the Center for Cancer and Blood Disorders practice. We applied continuous machine learning to predict risk of preventable harm (avoidable ACU) and generated patient-specific recommendations that nurses implemented to avert it. RESULTS: Patient-centric interventions included medication/dosage changes, laboratory tests/imaging, physical/occupational/psychologic therapy referral, palliative care/hospice referral, and surveillance/observation. Nurses contacted patients every 1-2 weeks after initial outreach to assess and maintain adherence to recommended interventions. Per 100 unique OCM patients, monthly ED visits dropped from 13.7 to 11.5 (18%), a sustained month-over-month improvement. Quarterly admissions dropped from 19.5 to 17.1 (13%), a sustained quarter-over-quarter improvement. Overall, the practice realized potential annual savings of $2.8 million US dollars (USD) on avoidable ACU. CONCLUSION: The AI tool has enabled nurse case managers to identify and resolve critical clinical issues and reduce avoidable ACU. Effects on outcomes can be inferred from the reduction; targeting short-term interventions toward patients most at-risk translates to better long-term care and outcomes. QI projects involving predictive modeling of patient risk, prescriptive analytics, and nurse outreach may reduce ACU.

Clinical Outcomes for Plasma-Based Comprehensive Genomic Profiling Versus Standard-of-Care Tissue Testing in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced nonsquamous non-small cell lung cancer (aNSCLC). The NILE study was a prospective observational study that demonstrated noninferiority of cell-free circulating tumor DNA (cfDNA)-based tumor genotyping compared to tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed nonsquamous aNSCLC. As the cohort has matured, clinical outcomes data can now be analyzed. METHODS: This prospective, multicenter North American study enrolled patients with previously untreated nonsquamous aNSCLC who had standard of care (SOC) tissue genotyping performed and concurrent comprehensive cfDNA analysis (Guardant360). Patients with targetable genomic alterations, as defined by NCCN guidelines, who were treated with physician's choice of therapy had objective response rates, disease control rate, and time to treatment collected and compared to published outcomes. RESULTS: Among 282 patients, 89 (31.6%) had an actionable biomarker, as defined by NCCN, detected by tissue (21.3%) and/or cfDNA (27.3%) analysis. Sixty-one (68.5%) of these were treated with an FDA-approved targeted therapy guided by somatic genotyping results (EGFR, ALK, ROS1). Thirty-three patients were eligible for clinical response evaluation and demonstrated an objective response rate of 58% and disease control rate of 94%. Twenty-five (76%) and 17 (52%) achieved a durable response > 6 months and 12 months, respectively. The time to treatment (TtT) was significantly faster for cfDNA-informed biomarker detection as compared to tissue genotyping (18 vs. 31 days, respectively; P = .0008). CONCLUSIONS: cfDNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published targeted therapy outcomes with tissue profiling, even in community-based centers.

Real-world ibrutinib dose reductions, holds and discontinuations in chronic lymphocytic leukemia.

Aim: A retrospective chart review of ibrutinib-treated patients with chronic lymphocytic leukemia (CLL) was conducted. Patients & methods: Adults with CLL who initiated ibrutinib were followed for ≥6 months (n = 180). Results: Twenty-five percent of first-line ibrutinib patients experienced ≥1 dose reduction, mainly due to adverse events (AEs; 79%). Treatment discontinuations and dose holds occurred in 20 and 34% of patients, respectively, most commonly due to AEs (73 and 74%). Approximately one-quarter of relapsed/refractory ibrutinib patients experienced ≥1 dose reduction, mainly due to AEs (88%). Treatment discontinuation and dose holds occurred in 40% of patients (58 and 76% due to AEs, respectively). Conclusion: Dose reductions, holds and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice.

Lay abstract Chronic lymphocytic leukemia (CLL) is a cancer that develops from a type of white blood cells called 'B cells.' Ibrutinib is a targeted therapy that inhibits the activity of a protein called Bruton's tyrosine kinase, which plays a key role in CLL. Patients receiving ibrutinib treatment can experience side effects ('adverse events'). In addition, patients may need to reduce their drug dose ('dose reductions') or stop treatment ('discontinuations') for a variety of reasons. We reviewed patients' charts to describe dose reductions and discontinuations in ibrutinib-treated patients with CLL. Our results indicate that dose reductions and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice, and that the most common reason was adverse events.

Real-world performance of blood-based proteomic profiling in first-line immunotherapy treatment in advanced stage non-small cell lung cancer.

PURPOSE: Immune checkpoint inhibition (ICI) therapy has improved patient outcomes in advanced non-small cell lung cancer (NSCLC), but better biomarkers are needed. A clinically validated, blood-based proteomic test, or host immune classifier (HIC), was assessed for its ability to predict ICI therapy outcomes in this real-world, prospectively designed, observational study. MATERIALS AND METHODS: The prospectively designed, observational registry study INSIGHT (Clinical Effectiveness Assessment of VeriStrat® Testing and Validation of Immunotherapy Tests in NSCLC Subjects) (NCT03289780) includes 35 US sites having enrolled over 3570 NSCLC patients at any stage and line of therapy. After enrolment and prior to therapy initiation, all patients are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C). A prespecified interim analysis was performed after 1-year follow-up with the first 2000 enrolled patients. We report the overall survival (OS) of patients with advanced stage (IIIB and IV) NSCLC treated in the first-line (ICI-containing therapies n=284; all first-line therapies n=877), by treatment type and in HIC-defined subgroups. RESULTS: OS for HIC-H patients was longer than OS for HIC-C patients across treatment regimens, including ICI. For patients treated with all ICI regimens, median OS was not reached (95% CI 15.4 to undefined months) for HIC-H (n=196) vs 5.0 months (95% CI 2.9 to 6.4) for HIC-C patients (n=88); HR=0.38 (95% CI 0.27 to 0.53), p<0.0001. For ICI monotherapy, OS was 16.8 vs 2.8 months (HR=0.36 (95% CI 0.22 to 0.58), p<0.0001) and for ICI with chemotherapy OS was unreached vs 6.4 months (HR=0.41 (95% CI 0.26 to 0.67), p=0.0003). HIC results were independent of programmed death ligand 1 (PD-L1). In a subgroup with PD-L1 ≥50% and performance status 0-1, HIC stratified survival significantly for ICI monotherapy but not ICI with chemotherapy. CONCLUSION: Blood-based HIC proteomic testing provides clinically meaningful information for immunotherapy treatment decision in NSCLC independent of PD-L1. The data suggest that HIC-C patients should not be treated with ICI alone regardless of their PD-L1 expression.

Telehealth in Oncology: ASCO Standards and Practice Recommendations.

PURPOSE: To provide standards and practice recommendations specific to telehealth in oncology. METHODS: A systematic review of the literature on telehealth in oncology was performed, including the use of technologies and telecommunications systems, and other electronic methods of care delivery and sharing of information with patients. The evidence base was combined with the opinion of the ASCO Telehealth Expert Panel to develop telehealth standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The Expert Panel determined that general guidance on implementing telehealth across general and specialty settings has been published previously and these resources are endorsed. A systematic search for studies on topics specific to oncology resulted in the inclusion of two clinical practice guidelines, 12 systematic reviews, and six primary studies. STANDARDS AND GUIDANCE: Standards and guidance are provided for which patients in oncology can be seen via telehealth, establishment of the doctor-physician relationship, role of allied health professionals, role of advanced practice providers, multidisciplinary cancer conferences, and teletrials in oncology. Additional information is available at www.asco.org/standards.

Occupational and Personal Consequences of the COVID-19 Pandemic on US Oncologist Burnout and Well-Being: A Study From the ASCO Clinician Well-Being Task Force.

INTRODUCTION: The COVID-19 pandemic is an unprecedented global crisis profoundly affecting oncology care delivery. PURPOSE: This study will describe the occupational and personal consequences of the COVID-19 pandemic on oncologist well-being and patient care. MATERIALS AND METHODS: Four virtual focus groups were conducted with US ASCO member oncologists (September-November 2020). Inquiry and subsequent discussions centered on self-reported accounts of professional and personal COVID-19 experiences affecting well-being, and oncologist recommendations for well-being interventions that the cancer organization and professional societies (ASCO) might implement were explored. Qualitative interviews were analyzed using Framework Analysis. RESULTS: Twenty-five oncologists were interviewed: median age 44 years (range: 35-69 years), 52% female, 52% racial or ethnic minority, 76% medical oncologists, 64% married, and an average of 51.5 patients seen per week (range: 20-120). Five thematic consequences emerged: (1) impact of pre-COVID-19 burnout, (2) occupational or professional limitations and adaptations, (3) personal implications, (4) concern for the future of cancer care and the workforce, and (5) recommendations for physician well-being interventions. Underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment. Oncologists noted personal and familial stressors related to COVID-19 exposure fears and loss of social support. Many participants strongly considered working part-time or taking early retirement. Yet, opportunities arose to facilitate personal growth and rise above pandemic adversity, fostering greater resilience. Recommendations for organizational well-being interventions included psychologic or peer support resources, flexible time-off, and ASCO and state oncology societies involvement to develop care guidelines, well-being resources, and mental health advocacy. CONCLUSION: Our study suggests that the COVID-19 pandemic has adversely affected oncologist burnout, fulfillment, practice health, cancer care, and workforce. It illuminates where professional organizations could play a significant role in oncologist well-being.

Creating a Blueprint of Well-Being in Oncology: An Approach for Addressing Burnout From ASCO's Clinician Well-Being Taskforce.

Optimizing the well-being of the oncology clinician has never been more important. Well-being is a critical priority for the cancer organization because burnout adversely impacts the quality of care, patient satisfaction, the workforce, and overall practice success. To date, 45% of U.S. ASCO member medical oncologists report experiencing burnout symptoms of emotional exhaustion and depersonalization. As the COVID-19 pandemic remains widespread with periods of outbreaks, recovery, and response with substantial personal and professional consequences for the clinician, it is imperative that the oncologist, team, and organization gain direct access to resources addressing burnout. In response, the Clinician Well-Being Task Force was created to improve the quality, safety, and value of cancer care by enhancing oncology clinician well-being and practice sustainability. Well-being is an integrative concept that characterizes quality of life and encompasses an individual's work- and personal health-related environmental, organizational, and psychosocial factors. These resources can be useful for the cancer organization to develop a well-being blueprint: a detailed start plan with recognized strategies and interventions targeting all oncology stakeholders to support a culture of community in oncology.

Guidance on Implementing an Oral Chemotherapy Drug Repository Program in a Medically Integrated Pharmacy Setting.

Oncology drug repository programs allow patients to donate oral chemotherapy that can be redispensed to patients in need and could ultimately reduce drug waste. Medically integrated pharmacies can serve as a platform for drug repository programs because of the integration of healthcare providers and pharmacists at one location, facilitating an effective transition from donation to redispensing. Before implementing a program, pharmacies should consider state laws regarding who can donate medications, the type of setting (including open or closed systems), as well as how to assess the quality of the medication donated, expiration dates, storing and maintenance of a separate inventory, written policies and procedures, and a priority list for dispensing medications to patients. In this article, we provide the initial steps to assist states and oncology pharmacists interested in developing a drug repository program.

Nanoparticle Albumin-bound Paclitaxel Plus Carboplatin Induction Followed by Nanoparticle Albumin-bound Paclitaxel Maintenance in Squamous Non-Small-cell Lung Cancer (ABOUND.sqm): A Phase III Randomized Clinical Trial.

BACKGROUND: We evaluated maintenance nanoparticle albumin-bound (nab) paclitaxel in the treatment of advanced squamous non-small-cell lung cancer. PATIENTS AND METHODS: Patients with treatment-naive squamous non-small-cell lung cancer received four 21-day cycles of nab-paclitaxel 100 mg/m2 on days 1, 8, 15 plus carboplatin area under the curve 6 on day 1 as induction therapy. Patients without disease progression after induction were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m2 (days 1 and 8 every 21 days) plus best supportive care (BSC) or BSC alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety and overall survival (OS). RESULTS: Overall, 420 patients had received induction therapy; 202 (nab-paclitaxel plus BSC, 136; BSC, 66) had received maintenance therapy. Enrollment was discontinued after a preplanned interim futility analysis (patients could remain in the study at the investigator's discretion). The median PFS was 3.12 months for nab-paclitaxel plus BSC and 2.60 months for BSC; the difference was not statistically significant (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61-1.19; P = .36). The median OS (median follow-up, 24.2 months) was 17.18 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.70; 95% CI, 0.48-1.02; nominal P = .07). An updated analysis (median follow-up, 28.4 months) revealed a median OS of 17.61 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.68; 95% CI, 0.47-0.98; nominal P = .037). The most frequent grade 3 and 4 treatment-emergent adverse events for the entire study were neutropenia (53.1% [nab-paclitaxel plus BSC] vs. 50.0% [BSC]) and anemia (33.1% [nab-paclitaxel plus BSC] vs. 32.3% [BSC]). Only peripheral neuropathy had occurred in ≥ 5% of patients during maintenance therapy (13.1%; nab-paclitaxel plus BSC). CONCLUSIONS: The results of the ABOUND.sqm did not meet the primary endpoint of PFS. An updated OS analysis revealed a trend favoring nab-paclitaxel plus BSC.

Prevalence and predictors of patients reporting adverse drug reactions to health care providers during oral targeted cancer treatment.

BACKGROUND: Pharmacovigilance is a critical component to facilitate clinicians' decision-making to alter or discontinue therapy. However, self-administration of oral targeted therapy (OTT) requires fewer clinical visits than parenteral infusions, potentially leading to an increase in the under-reporting of adverse drug reactions (ADRs). OBJECTIVE(S): To identify factors associated with patients reporting ADRs to their health care provider (HCP) and to identify the prevalence of unreported ADRs while on OTT. METHODS: Patients aged ≥18 years who received care from a community oncology clinic and newly prescribed an OTT between August 1, 2018, and October 31, 2018, were included. Six-monthly follow-up calls were conducted by the pharmacy staff to assess for gradable ADRs-validated by the NCI Common Terminology Criteria for Adverse Events-and ungradable ADRs. Descriptive analysis was used to analyze the prevalence of unreporting ADRs, and a multivariate logistic regression model was utilized to evaluate predictors of reporting ADRs to an HCP. Predictors included sociodemographic factors, severity of ADRs, insurance type, pharmacy setting, type of OTT, and the number of prescribed medications RESULTS: Of the 76 patients analyzed, the mean age was 63.32 ±11.55 years, 84.2% were women, 68.8% were non-Hispanic white, and 76.3% had breast cancer. During the follow-up calls, 306 ADRs were identified and 22.2% were not previously reported to an HCP. Of the unreported gradable ADRs, 63.2% were grade 1, 19.3% were grade 2, and 17.5% were grade 3. We found that for every 1-year increase in age, there was a 5% decrease in the likelihood of reporting ADRs (95% CI, 0.91-0.99), and men were 11.4 times more likely to report ADRs (95% CI, 1.29-100.8). CONCLUSION: Follow-up calls served as an outlet to collect pharmacovigilance data by identifying over 20% of unreported ADRs to HCPs, in which over one-third were moderate to severe. However, future studies are needed to further understand the statistically significant differences found in under-reporting for women and the older population.

Factors associated with adherence to follow-up calls in cancer patients receiving care at a community oncology practice.

BACKGROUND: Follow-up calls in the oncology setting are frequently used to augment care and encourage oral antineoplastic adherence. However, limited data are available on patient populations that would benefit from this intervention versus populations that may require alternative interventions. The purpose of this study was to identify characteristics among patients on oral antineoplastic agents that influence their likelihood to respond to follow-up calls. METHODS: Patients receiving care from one of the eight community oncology clinics within the same branch were analyzed. Patients were included if they were ≥18 years, received a new oral antineoplastic agent that was electronically prescribed between August 2018-October 2018, and picked up their first fill from their pharmacy of choice. Patients received up to six follow-up calls after picking up their first prescription. Calls were categorized as adherent (≥3 monthly interactions) or non-adherent (<3 monthly interactions). Logistic regression models were used to evaluate factors associated with follow-up call adherence. Factors included demographics, cancer stage, marital status, employment, pharmacy setting (internal pharmacy versus external pharmacy), and insurance used by the patient. Descriptive analysis was performed to analyze response rates, cancer diagnosis, and to determine the best time and day patients responded to follow-up calls. RESULTS: Data from 125 patients were analyzed, of which 65 patients (52%) were adherent to follow-up calls and the mean response rate over six months was 45% (range: 35% -- 54%). High success rates for follow-up calls were seen between 12-3 pm and on Tuesdays and Thursdays. After adjusting for covariates, patients with stage III-IV were 89% less likely to respond to follow-up calls compared to those with stage 0-II (95% CI: 0.02-0.64; p = 0.01), patients with commercial insurance were 79% less likely to adhere to follow-up calls compared to those on government insurance (95% CI: 0.06-0.71; p = 0.01), and patients using an external pharmacy had a 2.8 times increase odds of being adherent (95% CI 0.98-8.34; p = 0.05). All other factors were not significant. CONCLUSIONS: For patients taking oral antineoplastics, non-adherence to follow-up calls was observed in more than 45% of patients receiving care from a community oncology clinic. Findings demonstrated that those with advanced stages of cancer, on commercial insurance, and going to an internal pharmacy were at higher risk for not adhering to follow up calls. Therefore, alternative methods for managing adherence and side effects in these populations are warranted.

Safety and Efficacy of Nivolumab in Patients With Advanced Clear Cell Renal Cell Carcinoma: Results From the Phase IIIb/IV CheckMate 374 Study.

BACKGROUND: The open-label, phase IIIb/IV CheckMate 374 study (NCT02596035) was conducted to validate the safety and efficacy of flat-dose nivolumab monotherapy 240 mg every 2 weeks (Q2W) in previously treated advanced/metastatic renal cell carcinoma (RCC). Three cohorts included patients with predominantly clear cell histology, non-clear cell histologies, or brain metastases. We report safety and efficacy from the CheckMate 374 advanced clear cell RCC (ccRCC) cohort. PATIENTS AND METHODS: Eligible patients received prior treatment regimens (1-2 antiangiogenic; 0-3 systemic) with progression on/after last treatment and ≤ 6 months of enrollment. Patients received nivolumab 240 mg Q2W for ≤ 24 months or until confirmed progression/unacceptable toxicity. The primary endpoint was incidence of high-grade (grade 3-5) immune-mediated adverse events (IMAEs). Exploratory endpoints included objective response rate, progression-free survival, and overall survival. RESULTS: Ninety-seven patients had advanced predominantly ccRCC; 75.3% received only 1 prior systemic regimen in the advanced/metastatic setting. After a median follow-up of 17 months (range, 0.4-26.9 months), no grade 5 IMAEs occurred, and 9.3% of patients reported grade 3/4 IMAEs (hepatitis, 4.1%; diabetes mellitus, 2.1%; nephritis and renal dysfunction, 1.0%; rash, 1.0%; adrenal insufficiency, 1.0%). The objective response rate was 22.7% (95% confidence interval [CI], 14.8%-32.3%). Three patients had a complete response; 19 had partial responses. The median progression-free survival was 3.6 months (95% CI, 2.0-5.5 months). The median overall survival was 21.8 months (95% CI, 17.4 months to not estimable). CONCLUSIONS: This study validates the safety and efficacy of nivolumab 240 mg Q2W flat-dose monotherapy for previously treated advanced ccRCC and adds to previous safety and efficacy data using the 3 mg/kg Q2W dose.

Updates to the ASCO Patient-Centered Oncology Payment Model.

The past decade has seen considerable innovation in the delivery of care and payment in oncology. Key initiatives have included the development of oncology medical home care delivery standards, the Medicare Oncology Care Model, and multiple commercial payer initiatives. Looking forward, our next challenge is to reflect on lessons learned from these limited-scale demonstration projects and work toward models that are scalable and sustainable and reflect true collaboration between payers and providers sharing common objectives and methods to advance cancer care delivery. To this end, ASCO continues its work on care delivery standards, quality measurement, and alternative payment models. Over the past year, ASCO has received input from physicians, administrators, payers, and employers to update its Patient-Centered Oncology Payment (PCOP) model. PCOP incorporates current work on provider-payer collaboration, the oncology medical home, and the value of clinical pathways and recognizes the need for common quality measurement, performance methodology, and payment structure across multiple sources of payment. The following represents a summary of the entire model. The model includes chapters on PCOP communities, clinical practice transformation, payment methodology, consolidated payments for oncology care, performance methodology, and implementation considerations. In future work, ASCO will continue its support of the PCOP model, including further development of care delivery standards, quality measures, and technology solutions (eg, CancerLinQ).

A Randomized, Double-Blinded, Phase II Trial of Carboplatin and Pemetrexed with or without Apatorsen (OGX-427) in Patients with Previously Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer: The SPRUCE Trial.

BACKGROUND: This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein (Hsp) 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). METHODS: Patients were randomized 1:1 to Arm A (carboplatin/pemetrexed plus apatorsen) or Arm B (carboplatin/pemetrexed plus placebo). Treatment was administered in 21-day cycles, with restaging every two cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and during treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, and toxicity. RESULTS: The trial enrolled 155 patients (median age 66 years; 44% Eastern Cooperative Oncology Group performance status 0). Toxicities were similar in the 2 treatment arms; cytopenias, nausea, vomiting, and fatigue were the most frequent treatment-related adverse events. Median PFS and OS were 6.0 and 10.8 months, respectively, for Arm A, and 4.9 and 11.8 months for Arm B (differences not statistically significant). Overall response rates were 27% for Arm A and 32% for Arm B. Sixteen patients (12%) had high serum levels of Hsp27 at baseline. In this small group, patients who received apatorsen had median PFS of 10.8 months, and those who received placebo had median PFS 4.8 months. CONCLUSION: The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting. IMPLICATIONS FOR PRACTICE: This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting.

Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non-small Cell Lung Cancer.

PURPOSE: Complete and timely tissue genotyping is challenging, leading to significant numbers of patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) being undergenotyped for all eight genomic biomarkers recommended by professional guidelines. We aimed to demonstrate noninferiority of comprehensive cell-free DNA (cfDNA) relative to physician discretion standard-of-care (SOC) tissue genotyping to identify guideline-recommended biomarkers in patients with mNSCLC. PATIENTS AND METHODS: Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretion SOC tissue genotyping submitted a pretreatment blood sample for comprehensive cfDNA analysis (Guardant360). RESULTS: Among 282 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 60 patients versus 77 cfDNA identified patients (21.3% vs. 27.3%; P < 0.0001 for noninferiority). In tissue-positive patients, the biomarker was identified alone (12/60) or concordant with cfDNA (48/60), an 80% cfDNA clinical sensitivity for any guideline-recommended biomarker. For FDA-approved targets (EGFR, ALK, ROS1, BRAF) concordance was >98.2% with 100% positive predictive value for cfDNA versus tissue (34/34 EGFR-, ALK-, or BRAF-positive patients). Utilizing cfDNA, in addition to tissue, increased detection by 48%, from 60 to 89 patients, including those with negative, not assessed, or insufficient tissue results. cfDNA median turnaround time was significantly faster than tissue (9 vs. 15 days; P < 0.0001). Guideline-complete genotyping was significantly more likely (268 vs. 51; P < 0.0001). CONCLUSIONS: In the largest cfDNA study in previously untreated mNSCLC, a validated comprehensive cfDNA test identifies guideline-recommended biomarkers at a rate at least as high as SOC tissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping.See related commentary by Meador and Oxnard, p. 4583.