Abstract
Direct intratumoral delivery of immunotherapies is a compelling approach to overcoming barriers to systemic immunotherapy efficacy. While the use of intratumoral delivery of immunotherapy drugs is increasing rapidly in both the investigational and standard of care domains, the feasibility and safety of these interventions, particularly for deeper lesions that require image-guidance, remain unknown. To address current knowledge gaps in image-guided techniques for intratumoral immunotherapy delivery and the safety of these interventions. This case series study was performed at a single tertiary cancer center over a 2-year period from January 2016 to January 2018. Patients were followed until January 2019. All patients who underwent image-guided intratumoral delivery of immunotherapy agents in the standard of care, off-label, or investigational setting during the study period were included. Data were analyzed from February 1 to June 1, 2019. Image-guided biopsies and intratumoral injections of immunotherapies across several clinical trials as well as standard of care talimogene laherparepvec therapy. Technical success, defined as the delivery of the prescribed injectate volume in its entirety, for image-guided biopsy and injections and procedure-related adverse events. A total of 85 patients (median [interquartile range] age, 61 [47-71] years; 42 [52%] men) underwent 498 encounters during the study period. These encounters comprised 327 image-guided intratumoral investigational agent injections in 67 patients in clinical trials, including 33 patients with melanoma (50%), 14 patients with sarcoma (21%), 3 patients with ovarian cancer (4.5%), 2 patients with breast cancer (3%), and 2 patients with colon cancer (3%). An additional 18 patients with melanoma underwent 113 image-guided talimogene laherparepvec injections. There were no adverse events reported related to the technical component of the procedure, specifically needle insertion or biopsy. Serious adverse events (Common Terminology Criteria for Adverse Events score ≥3), including dyspnea and severe flu-like symptoms developing within 24 hours of the injection and requiring hospitalization, occurred after 3 of 327 investigational agent injections (2%) and 4 of 113 talimogene laherparepvec injections (4%). The findings of this case series study suggest that intratumoral injections of immunotherapies were feasible across a range of histological conditions and target organs. Immediate postdelivery anticipated adverse events occurred in a small number of instances. Performing physicians should have the necessary safeguards in place to respond as needed. Optimal methods for intratumoral drug delivery remain unresolved, and efforts to standardize drug delivery techniques are required.
Highlights
The conventional method for delivery of chemotherapy via intravenous administration allows for the distribution of the treatment drug throughout the body, but known challenges limit its effectiveness
Serious adverse events (Common Terminology Criteria for Adverse Events score Ն3), including dyspnea and severe flu-like symptoms developing within 24 hours of the injection and requiring hospitalization, occurred after 3 of 327 investigational agent injections (2%) and 4 of 113 talimogene laherparepvec injections (4%)
The findings of this case series study suggest that intratumoral injections of immunotherapies were feasible across a range of histological conditions and target organs
Summary
The conventional method for delivery of chemotherapy via intravenous administration allows for the distribution of the treatment drug throughout the body, but known challenges limit its effectiveness. Drug penetration into the tumor tissue can be inadequate owing to inherent barriers imposed by the tumor microenvironment.[1,2] indiscriminate exposure of the nontumorous compartment often adversely influences the agents’ effectiveness or results in prohibitive toxic effects. Local intratumoral injection of anticancer therapies is a logical solution to overcoming these barriers to drug delivery.[3] With the recent advancements in immune-based cancer therapies, there has been a resurgence of interest in the delivery of therapeutic agents directly into tumors, either as primary therapy or as an adjunct agent in combination with systemic immunotherapy.[4] By successfully delivering a high concentration of immunostimulatory agents into a tumor site, local intratumoral drug delivery has the potential to drive sustained, systemic immune responses.[5]
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