Management of Adverse Events in Early Clinical Trials by Advanced Practice Providers in the Outpatient Setting: The University of Texas MD Anderson Cancer Center Experience.

Background: Advanced practice providers (APPs) play important roles in enrolling, educating, and caring for patients in clinical trials. However, much remains unknown about the role of APPs in managing adverse events (AEs) in early (phase I to II) clinical trials. In this study, we assessed the outpatient management of grade 3 to 4 AEs by APPs in early trials and characterized the workflow of our APP Phase I to II Fast Track (FT) Clinic. Patients and Methods: We retrospectively reviewed records of patients with advanced or metastatic solid tumors enrolled in phase I to II clinical trials who were seen by APPs from September 2017 to August 2018 in the APP phase I to II FT clinic in the Department of Investigational Cancer Therapeutics. Results: A total of 808 patients enrolled in 159 clinical trials were seen in 2,697 visits (median 3 visits per patient; range 1-28) by 10 APPs. Treatment was interrupted in 6.9% of visits, and grade 3 to 4 AEs were seen in 5.4% of visits; however, patients from 1.4% of visits were sent to the emergency center (EC) and/or admitted. Patients referred to the EC and/or admitted were more likely to have baseline hypoalbuminemia, high lactate dehydrogenase, and poor Eastern Cooperative Oncology Group performance status (i.e., ECOG > 1; p < .001). There were no associations between EC referral and gender, APP years of experience, or type of treatment. Conclusions: The APP Phase I to II FT Clinic has an important role in the management of AEs by APPs in early clinical trials in the outpatient setting, potentially avoiding EC visits and admissions.

A Rare Event of Liver Dysfunction on Sotorasib and Management Strategy.

KRAS mutations are the most common alteration in human cancers, accounting for approximately 30% of mutations in multiple cancer types, including colorectal, pancreatic, non-small lung cancer, and ovarian. Of these, the KRAS p.G12C mutation occurs in 13% of non-small lung cancers and 1% to 3% of colorectal and other cancers (Hong et al., 2020). With the approval of the direct KRAS p.G12C inhibitor sotorasib in early 2021, this first-in-class small-molecule agent has increased progression-free survival by 6.3 months in patients with p.G12C non-small cell lung cancer. Side effects associated with sotorasib have been mild, with the most frequent being diarrhea and nausea, but grade 3 to 4 toxicity has also been observed, which is clinically significant. Grade 3 toxicity related to aspartate aminotransferase and alanine aminotransferase is defined as an increase of more than 5 to 20 times the upper limit of normal (ULN), while grade 4 is more than 20 times the ULN. This is significant and requires withholding treatment as it can be life-threatening in some cases. The following case study outlines a patient who developed abnormal liver enzyme elevation while on the phase I clinical trial of sotorasib, and the management of this event.

Post-Discharge Survival Outcomes of Patients with Advanced Cancer from the University of Texas MD Anderson Cancer Center Investigational Cancer Therapeutics (Phase I Trials) Inpatient Unit.

BACKGROUND: Patients with advanced cancer who progress on standard therapy are potential candidates for phase I clinical trials. Due to their aggressive disease and complex comorbid conditions, these patients often need inpatient admission. This study assessed the outcomes of such patients after they were discharged to hospice care. PATIENTS AND METHODS: We performed a retrospective analysis of patients with solid tumor malignancies who were discharged to hospice care from the inpatient service. RESULTS: One hundred thirty-three patients were included in the study cohort. All patients had metastatic disease and an Eastern Cooperative Oncology Group performance status ≥3. The median survival after discharge to hospice from an inpatient setting was 16 days, with a survival rate of 5% at 3 months after discharge. The median survival after the last cancer treatment was 46 days, with survival of 17% at 3 months, and 5% at 6 months. Patients with lactate dehydrogenase (LDH) >618 IU/L had a median post-discharge survival of 11 days versus 20 days for patients with LDH ≤618 IU/L. CONCLUSIONS: Patients with metastatic cancer participating in phase I trials who have poor performance status and require inpatient admission have a very short survival after discharge to hospice. A high LDH level predicts an even shorter survival.