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Introduction: Eribulin was approved by the FDA in 2010 for the treatment of metastatic breast cancer (MBC) in the United States (US). More recently, several immuno-oncology (IO) and antibody–drug conjugate (ADC) regimens have been approved for MBC. We assessed the treatment patterns and clinical outcomes in MBC patients treated with eribulin following treatment with an IO or ADC in US clinical practice.Materials and Methods: In a retrospective patient medical chart review study, patients with MBC, aged ≥ 18 years, who initiated eribulin therapy between March 1, 2019, and September 30, 2020, treated with either prior IO or ADC in the metastatic setting were included. Patient demographics, treatment characteristics, and clinical outcomes were analyzed descriptively. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan–Meier analyses.Results: In the study population (N=143), median age at eribulin initiation was 62 years; 64% were Caucasian, and 67% had triple-negative MBC (TNBC). Eribulin therapy was used in the second to fifth line of therapy in the metastatic setting; median treatment duration was 7.2 months. The overall response rate for eribulin was 59.4%. Median rwPFS and OS from eribulin initiation were 21.4 months (95% CI, 12.9-not estimable [NE]) and 24.2 months (95% CI, 17.5-NE), respectively. In patients with TNBC, median rwPFS and OS from eribulin initiation were 12.0 months (95% CI, 8.8-NE) and 18.3 months (95% CI, 14.9-NE), respectively.Conclusion: These real-world data provide evidence for the clinical effectiveness outcomes of eribulin treatment among MBC patients previously treated with an IO or ADC. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent advances in immunotherapeutic approaches have spanned different tumor types including head and neck cancer. HPV-related head and Neck Cancers are virally driven tumors with notable immune characteristics and recent advances in immune targeting that desrve a closer examination. We aimed in this comprehensive review to offer a description of recent advances in immunotherapeutic applications in this disease. Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer. [ABSTRACT FROM AUTHOR]

Background: The availability of new immuno-oncology therapeutics markedly impacts oncology clinicians' treatment decision-making. To effectively support healthcare professionals (HCPs) in their practice, it is important to better understand the challenges and barriers that can accompany the introduction of these agents. This study aimed to establish the types and causes of clinical challenges posed by the introduction of new immuno-oncology agents. Methods: The mixed-methods design included qualitative in-depth interviews and group discussions with HCPs, in which participants discussed clinical challenges and potential underlying reasons for these challenges. Qualitative findings informed a quantitative survey. This survey investigated the extent and distribution of challenges using HCPs' self-rating of knowledge, skill, confidence, and exposure to system-level effects. These two phases were conducted sequentially with distinctly stratified samples of oncologists, nurse practitioners (NPs), physician assistants (PAs), pathologists, clinical pharmacists, interventional radiologists, rheumatologists, pulmonologists, and emergency department physicians. Participants were from the United States and had various levels of clinical experience and represented both academic and community-based settings. Results: The final sample included 107 HCPs in the qualitative phase and 554 in the quantitative phase. Analyses revealed clinical challenges related to the use of pharmacodiagnostics. For example, 47% of pathologists and 42% of oncologists reported skill gaps in identifying the appropriate marker and 46% of oncologists, 61% of PAs, 66% of NPs, 74% of pulmonologists and 81% of clinical pharmacists reported skill gaps in selecting treatment based on test results. Challenges also emerged regarding the integration of immuno-oncology agents, as oncologists, rheumatologists, pulmonologists, clinical pharmacists, PAs, and NPs reported knowledge gaps (74-81%) of the safety profiles of recently approved agents. In addition, 90% of clinical pharmacists reported skill gaps weighing the risks and benefits of treating patients with immuno-oncology agents while affected by lupus. Finally, patient communication challenges were identified: HCPs reported difficulties discussing essential aspects of immunotherapy to patients as well as how they might compare to other types of therapies. Conclusion: The challenges highlighted in this study reveal substantial educational gaps related to the integration of immuno-oncology agents into practice for various groups of HCPs. These findings provide a strong base of evidence for future educational initiatives. [ABSTRACT FROM AUTHOR]

Background A nivolumab monotherapy flat-dosing regimen of 480 mg every 4 weeks (Q4W) has been approved in several markets, including the United States, Canada, and European Union, as an alternative dosing regimen for several indications. Approvals of this Q4W regimen were based on population pharmacokinetic (PK) analyses, established flat exposure–response relationships, and clinical safety. The objective of this study was to compare the PK exposure of 480 mg Q4W with 3 mg/kg every 2 weeks (Q2W) and 240 mg Q2W using modeling and simulation, and to evaluate clinical safety of the Q4W regimen. Patients and methods Nivolumab PK exposure for the 480 mg Q4W schedule was simulated for 3817 patients across multiple tumor types and compared with those for the 3 mg/kg Q2W and 240 mg Q2W schedules. The safety profile of the Q4W schedule was assessed by analysis of clinical data from 61 patients who transitioned to nivolumab 480 mg Q4W from 3 mg/kg Q2W during four phase III clinical trials. Results Compared with 3 mg/kg Q2W, nivolumab 480 mg Q4W produced similar time-averaged concentration, approximately 16% lower trough concentration, and 45% higher peak concentration at steady state. The peak concentration for 480 mg Q4W was significantly lower than that of 10 mg/kg Q2W, a dose previously shown to have an acceptable tolerability and safety profile. Treatment-related adverse events (TRAEs) that started after transitioning from 3 mg/kg Q2W to 480 mg Q4W were reported in 14.8% of patients, with 1.6% of patients reporting grades 3–4 TRAEs. Pooled safety data for these patients are consistent with those for the 3 mg/kg Q2W schedules, and no new safety signals were identified. Conclusions The time-averaged steady-state exposure and safety profile of nivolumab 480 mg Q4W are consistent with that of 3 mg/kg Q2W across multiple tumor types. Nivolumab 480 mg Q4W represents a new dosing schedule option, and in addition to 240 mg Q2W, provides convenience and flexibility for patient care. Clinical trial numbers NCT01721772, NCT01668784, NCT01673867, NCT01642004 [ABSTRACT FROM AUTHOR]

Purpose: Treatments for advanced non-small cell lung cancer (NSCLC) have evolved to include targeted and immuno-oncology therapies, which have demonstrated clinical benefits in clinical trials. However, few real-world studies have evaluated these treatments in the first-line setting., Methods: Adult patients with advanced NSCLC who initiated first-line treatment with chemotherapy, targeted therapies (TT), or immuno-oncology-based regimens in the US Oncology Network (USON) between March 1, 2015, and August 1, 2018, were included and followed up through February 1, 2019. Data were sourced from structured fields of USON electronic health records. Patient and treatment characteristics were assessed descriptively, with Kaplan-Meier methods used to evaluate time-to-event outcomes, including time to treatment discontinuation (TTD) and overall survival (OS). Adjusted Cox regression analyses and inverse probability of treatment weighting (IPTW) were performed to control for covariates that may have affected treatment selection and outcomes., Results: Of 7746 patients, 75.6% received first-line systemic chemotherapy, 11.7% received immuno-oncology monotherapies, 8.5% received TT, and 4.2% received immuno-oncology combination regimens. Patients who received immuno-oncology monotherapies had the longest median TTD (3.5 months; 95% confidence interval [CI], 2.8-4.2) and OS (19.9 months; 95% CI, 16.6-24.1). On the basis of multivariable Cox regression and IPTW, immuno-oncology monotherapy was associated with reduced risk of death and treatment discontinuation relative to other treatments., Conclusion: These results suggest that real-world outcomes in this community oncology setting improved with the introduction of immuno-oncology therapies. However, clinical benefits are limited in certain subgroups and tend to be reduced compared with clinical trial observations.

Aim: Assessing treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma clinical practice. Materials & methods: A US cross-sectional physician survey conducted February-September 2019. Results: Surveyed physicians reported first-line treatment of 445 patients involving tyrosine kinase inhibitor monotherapy (51.0%), immuno-oncology (IO/IO combination) therapy (25.8%) or other regimens (23.1%). A total of 60.9% had physician-assessed IMDC risk. Of these 61.9, 50.9 and 27.6% of patients with favorable, intermediate and poor risk, respectively, received tyrosine kinase inhibitor monotherapy. A total of 16.7, 26.9 and 34.5% of patients with favorable, intermediate or poor risk received IO/IO combination therapy. Complete/partial responses (∼35% patients) remained comparable across first-line treatments. Conclusion: Guideline-recommended therapies are not widely prescribed. Many patients experienced poor clinical outcomes highlighting a need for more effective treatments.

The rapid development of effective immunotherapy using immune-checkpoint inhibitors (ICIs) against many different cancer types opened a new front in cancer treatment. Immunotherapy is undoubtedly one of the biggest breakthroughs in cancer therapy within the past decade. The identification of predictive biomarkers to select the patients most likely to respond to ICI monotherapies or emerging combination therapies remains one of the major unmet needs for the oncology community.This chapter provides an overview of existing and emerging biomarkers associated with ICI response. Additionally, using several case studies of FDA approved or authorized in vitro diagnostic oncology devices, this chapter also provides an overview of analytical and clinical validation considerations of diagnostic tests for immuno-oncology biomarkers.

Background: A nivolumab dosage regimen of 480 mg intravenously (i.v.) every 4 weeks (Q4W) was approved by FDA for the majority of the approved indications for nivolumab., Methods: The proposed new dosage regimen was supported by pharmacokinetic modeling and simulation, dose/exposure-response relationships for efficacy and safety in the indicated patient populations, and the clinical safety data with the 480 mg Q4W dosage regimen. Pharmacokinetic exposures achieved with 480 mg Q4W were predicted for 4166 patients in 21 clinical studies with various types of solid and hematological tumors. Exposure-response analyses were conducted to predict 480 mg Q4W safety and efficacy across all FDA-approved indications for nivolumab., Results: For the overall population, the geometric mean exposure achieved with 480 mg i.v. Q4W was 5.2% higher for steady state Cavg and 15.6% lower for Ctrough than those with 3 mg/kg i.v. Q2W, the approved dosage regimen. The simulated concentration-time course achieved with 480 mg Q4W regimen was below the median concentration achieved with 10 mg/kg i.v. Q2W that was also studied in clinical trials. The predicted probability of adverse events was similar between 480 mg Q4W and that observed with the 3 mg/kg Q2W regimen. Efficacy results were found to be similar between Q2W and Q3W dosage regimens in patients with renal cell carcinoma. The predicted efficacy for each indication suggested that the efficacy with 480 mg Q4W is unlikely to be compromised compared with that observed with 3 mg/kg Q2W., Conclusions: The model-informed analyses of predicted exposure, efficacy and safety based on data from extensive clinical experience with nivolumab suggest that the benefit-risk profile of 480 mg Q4W regimen is comparable to the approved 3 mg/kg Q2W regimen, thus providing the regulatory basis for the approval of 480 mg Q4W regimen in the absence of clinical efficacy data with this new dosage regimen., (Published by Oxford University Press on behalf of the European Society for Medical Oncology 2019. This work is written by US Government employees and is in the public domain in the US.)