Type: Peer Reviewed Publications

PURPOSE As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed…

The breakthrough therapy designation (BTD) process was created to expedite clinical development timelines for drugs intended to treat serious conditions and preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies. This analysis demonstrates that BTD is a valuable tool for expediting approval of promising therapies in oncology. By comparing drugs indicated…

Abstract Recent approvals of novel therapeutics, including targeted small-molecules and immunotherapies, have significantly impacted cancer care. However, these advancements have not easily translated to new treatment options and approvals for pediatric cancer patients. The Research to Accelerate Cures and Equity (RACE) Act was signed into law in 2017 to accelerate the availability of drugs for…

Abstract Background Homologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of…

ABSTRACT Randomized controlled trials (RCTs) are the gold standard for evaluation of new medical products. However, RCTs may not always be ethical or feasible. In cases where the investigational product is available outside the trial (e.g., through accelerated approval), patients may fail to enroll in clinical trials or drop out early to take the investigational…

Background Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of…

Abstract Purpose: Restrictive clinical trial eligibility criteria (EC) limit the number of patients who can enroll and potentially benefit from protocol-driven, investigational treatment plans and reduce the generalizability of trial results to the broader population. Following publication of expert stakeholder recommendations for broadening EC in 2017, the American Society of Clinical Oncology (ASCO) and Friends…

Abstract Purpose: Performance status (PS) is one of the most common eligibility criteria. Many trials are limited to patients with high-functioning PS, resulting in important differences between trial participants and patient populations with the disease. In addition, existing PS measures are subjective and susceptible to investigator bias. Experimental Design: A multidisciplinary working group of the…

Abstract Purpose: Restrictive eligibility criteria induce differences between clinical trial and “real-world” treatment populations. Restrictions based on prior therapies are common; minimizing them when appropriate may increase patient participation in clinical trials. Experimental Design: A multi-stakeholder working group developed a conceptual framework to guide evaluation of prevailing practices with respect to using prior treatment as…

Abstract Purpose: In clinical research, eligibility criteria promote patient safety and optimize the evidence generated from clinical trials. However, overly stringent eligibility criteria, including laboratory requirements, may limit enrollment, resulting in delayed trial completion and potentially limiting applicability of trial results to a general practice population. Experimental Design: Starting in 2018, a working group consisting…