Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies.

INTRODUCTION: The development of molecularly targeted anticancer therapies and immunotherapy continues to revolutionize the treatment of cancer. FDA accelerated approvals of novel targeted therapies allowed for introduction of these agents into the clinic at a rapid rate. On-and off-target ocular toxicities are prevalent treatment-related adverse events of newer therapies including antibody drug conjugates (ADCs) and immunotherapy. Ocular toxicities associated with ADCs and immunotherapy have heterogeneous presentations and pathogenesis requiring unique and often complex monitoring, and management. AREAS COVERED: In this article, we provide an updated review of treatment-emergent ocular toxicity associated with new and novel oncologic therapies and summarize guidelines and best practice strategies for prevention, monitoring and management. A literature search was performed through PubMed, ClinicalTrials.gov, and FDA website (1 January 2017 to 10 May 2023) to identify relevant information. EXPERT OPINION: The implementation of a strategy for monitoring, prevention, and management of treatment-related ocular toxicities involves a multi-disciplinary, often cross-center approach. Communication with infusion nursing leadership, clinic staff, and eye care providers is crucial to the successful implementation of eye care plans to prevent and manage ocular toxicity.

Biosimilar strategic implementation at a large health system.

PURPOSE: This article highlights one health system's response to the market influx of biosimilars with the establishment of a process for formulary review and selection of preferred agents and support for therapeutic interchanges. SUMMARY: Through assessment of available literature, insurance payor coverage, and manufacturer-anticipated approvals of biosimilars, a strategic stance was developed to guide biosimilar order preparation, review, adoption, and implementation. The electronic medical record (EMR) is prepared for biosimilar implementation at least 6 to 12 months ahead of anticipated formulary review. The review includes assessment of a class (reference product and available biosimilars) after at least 2 biosimilars become available. Key health-system departments and clinicians are enlisted to support review of clinical, safety, and economic implications. Implementation of a preferred product relies on standard education, formulary availability, and staff awareness to address any perceived patient safety concerns and gather provider support. The standard steps developed now apply to all future biosimilar reviews, adoption plans, and ongoing monitoring. Barriers evaluated include changes in payor coverage and challenges in preparation of the EMR for future biosimilars, meeting precertification team education needs, and providing operational support for pharmacy inventory. CONCLUSION: To date, use of 5 preferred biosimilar products has led to significant cost savings to the institution, and the process has been endorsed by providers. The institution's successes can be attributed to clear communication with stakeholders and the development of a deliberate process, led by a multidisciplinary leadership team, for managing formulary, safety, and operational barriers in a thoughtful and systematic manner.

Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells.

The potential application of GPNMB/OA as a therapeutic target for lung cancer will require a greater understanding of the impact of GPNMB/OA ectodomain (ECD) protein shedding into tumor tissues. Thus, in this work we characterized GPNMB/OA expression and extent of shedding of its ECD protein while evaluating the impact on lung cancer progression using three non-small cell lung cancer (NSCLC) cell lines: A549, SK-MES-1 and calu-6. We observed a direct correlation (R2 = 0.89) between GPNMB/OA expression on NSCLC cells and the extent of GPNMB/OA ECD protein shedding. Meanwhile, siRNA-mediated knockdown of GPNMB/OA in cancer cells significantly reduced GPNMB/OA ECD protein shedding, migration, invasion and adhesion to extracellular matrix materials. Also, exogenous treatment of cancer cells (expressing low GPNMB/OA) with recombinant GPNMB/OA protein (rOA) significantly facilitated cell invasion and migration, but the effects of rOA was negated by inclusion of a selective RGD peptide. Further studies in athymic (nu/nu) mice-bearing calu-6 showed that intratumoral supplementation with rOA effectively facilitated in vivo tumor growth as characterized by a high number of proliferating cells (Ki67 staining) coupled with a low number of apoptotic cells. Taken together, our results accentuate the relevance of GPNMB/OA ECD protein shedding to progression of lung cancer. Thus, strategies that suppress GPNMB/OA expression on lung cancer cells as well as negate shedding of GPNMB/OA ECD protein are worthy of consideration in lung cancer therapeutics.