Mary Kate Kasler - Academia.edu (original) (raw)

Papers by Mary Kate Kasler

Research paper thumbnail of Clinical implications of drug‐induced liver injury in early‐phase oncology clinical trials

Cancer

Background: Data on drug-induced liver injury (DILI) and acute liver failure (ALF) on modern onco... more Background: Data on drug-induced liver injury (DILI) and acute liver failure (ALF) on modern oncologic phase I trials are limited, specifically regarding the incidence and resolution of DILI and safety of drug rechallenge. Methods: We reviewed all patients who were recruited to oncologic phase I trials between 2013 and 2017 at Memorial Sloan Kettering Cancer Center. Clinicopathologic data were extracted to characterize DILI and attribution was assessed using prospectively generated data during the studies. Logistic regression models were used to explore factors related to DILI and DILI recurrence after drug rechallenge. Results: Among 1670 cases recruited to 85 phase I trials, 81 (4.9%) developed DILI. The rate of DILI occurrence was similar between patients in immune-based trials and targeted therapy trials (5.0% vs. 4.9%), as was the median time to DILI (5.5 vs. 6.5 weeks, respectively; P = 0.48). Two patients (0.12%) met the criteria of Hs' law, although none developed ALF. DILI resolved in 96% of patients. Pretreatment factors did not predict for DILI development. Thirty-six of 81 patients underwent a drug rechallenge, of whom 28% developed DILI recurrence. Peak alanine aminotransferase during the initial DILI was associated with DILI recurrence (OR 1.04; 95% CI, 1.0 to 1.09; P = 0.035). Conclusions: On modern phase I oncology trials, DILI is uncommon, may occur at any time, and often resolves with supportive measures. Rechallenging after DILI is feasible; however, the high rate of DILI recurrence suggests that clinicians should consider the severity of the DILI episode and treatment alternatives.

Research paper thumbnail of Immune checkpoint inhibitors: An innovation in immunotherapy for the treatment and management of patients with cancer

Asia-Pacific Journal of Oncology Nursing, 2017

of immunotherapies reflects a promising new approach to cancer treatment involving activation of ... more of immunotherapies reflects a promising new approach to cancer treatment involving activation of the immune system against cancer. [2,3] The use of immunotherapy for cancer has become widespread in recent decades and is used to treat both solid Access this article online Quick Response Code:

Research paper thumbnail of Immune-Related Adverse Events in the Older Adult with Cancer Receiving Immune Checkpoint Inhibitor Therapy

Asia-Pacific Journal of Oncology Nursing

Objective: Older adults with cancer (OAC) may be at elevated risk for immune-related adverse even... more Objective: Older adults with cancer (OAC) may be at elevated risk for immune-related adverse events (irAEs) during immune checkpoint inhibitor (ICI) therapy due to the normal organ function changes of aging, as well as related to a higher prevalence of comorbid conditions compared to younger patients. The importance of high-quality nursing care cannot be overstated for this population, including proactive symptom assessment, management, and coordination of care. The purpose of this paper is to describe the unique challenges faced by OAC receiving ICI drugs. Methods: We present both a case study and the results of a single-institution retrospective study from a large, urban US National Cancer Institute– designated comprehensive cancer center. The retrospective study examined the frequency and intensity of irAEs experienced by patients aged 75 years or older who received ICI therapy between January 2016 and December 2018 for melanoma. Results: We reviewed the records of 38 OAC (age range 75–92 years) with locally advanced or metastatic melanoma who received pembrolizumab, nivolumab and/or ipilimumab. Median length of therapy was 7.4 months, and median time to onset of irAEs was 81 days. Approximately half (47%) of the patients experienced Grade 1–3 irAEs, and discontinued therapy related to inability to tolerate the ICI more frequently than was reported in clinical trials (24%). Conclusions: OAC who receive ICI therapy frequently experience irAEs that may result in treatment interruption, discontinuation or long-lasting toxicity. Nurses are well positioned to provide support to this vulnerable population.

Research paper thumbnail of Immune Checkpoint Inhibitors in Lung Cancer and Melanoma

Seminars in Oncology Nursing

Research paper thumbnail of Understanding and Managing Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Patients With Advanced Melanoma

Journal of the Advanced Practitioner in Oncology, 2017

Research paper thumbnail of Checkpoint Inhibitors: Common Immune-Related Adverse Events and Their Management


Clinical Journal of Oncology Nursing

Research paper thumbnail of Clinical implications of drug‐induced liver injury in early‐phase oncology clinical trials

Cancer

Background: Data on drug-induced liver injury (DILI) and acute liver failure (ALF) on modern onco... more Background: Data on drug-induced liver injury (DILI) and acute liver failure (ALF) on modern oncologic phase I trials are limited, specifically regarding the incidence and resolution of DILI and safety of drug rechallenge. Methods: We reviewed all patients who were recruited to oncologic phase I trials between 2013 and 2017 at Memorial Sloan Kettering Cancer Center. Clinicopathologic data were extracted to characterize DILI and attribution was assessed using prospectively generated data during the studies. Logistic regression models were used to explore factors related to DILI and DILI recurrence after drug rechallenge. Results: Among 1670 cases recruited to 85 phase I trials, 81 (4.9%) developed DILI. The rate of DILI occurrence was similar between patients in immune-based trials and targeted therapy trials (5.0% vs. 4.9%), as was the median time to DILI (5.5 vs. 6.5 weeks, respectively; P = 0.48). Two patients (0.12%) met the criteria of Hs' law, although none developed ALF. DILI resolved in 96% of patients. Pretreatment factors did not predict for DILI development. Thirty-six of 81 patients underwent a drug rechallenge, of whom 28% developed DILI recurrence. Peak alanine aminotransferase during the initial DILI was associated with DILI recurrence (OR 1.04; 95% CI, 1.0 to 1.09; P = 0.035). Conclusions: On modern phase I oncology trials, DILI is uncommon, may occur at any time, and often resolves with supportive measures. Rechallenging after DILI is feasible; however, the high rate of DILI recurrence suggests that clinicians should consider the severity of the DILI episode and treatment alternatives.

Research paper thumbnail of Immune checkpoint inhibitors: An innovation in immunotherapy for the treatment and management of patients with cancer

Asia-Pacific Journal of Oncology Nursing, 2017

of immunotherapies reflects a promising new approach to cancer treatment involving activation of ... more of immunotherapies reflects a promising new approach to cancer treatment involving activation of the immune system against cancer. [2,3] The use of immunotherapy for cancer has become widespread in recent decades and is used to treat both solid Access this article online Quick Response Code:

Research paper thumbnail of Immune-Related Adverse Events in the Older Adult with Cancer Receiving Immune Checkpoint Inhibitor Therapy

Asia-Pacific Journal of Oncology Nursing

Objective: Older adults with cancer (OAC) may be at elevated risk for immune-related adverse even... more Objective: Older adults with cancer (OAC) may be at elevated risk for immune-related adverse events (irAEs) during immune checkpoint inhibitor (ICI) therapy due to the normal organ function changes of aging, as well as related to a higher prevalence of comorbid conditions compared to younger patients. The importance of high-quality nursing care cannot be overstated for this population, including proactive symptom assessment, management, and coordination of care. The purpose of this paper is to describe the unique challenges faced by OAC receiving ICI drugs. Methods: We present both a case study and the results of a single-institution retrospective study from a large, urban US National Cancer Institute– designated comprehensive cancer center. The retrospective study examined the frequency and intensity of irAEs experienced by patients aged 75 years or older who received ICI therapy between January 2016 and December 2018 for melanoma. Results: We reviewed the records of 38 OAC (age range 75–92 years) with locally advanced or metastatic melanoma who received pembrolizumab, nivolumab and/or ipilimumab. Median length of therapy was 7.4 months, and median time to onset of irAEs was 81 days. Approximately half (47%) of the patients experienced Grade 1–3 irAEs, and discontinued therapy related to inability to tolerate the ICI more frequently than was reported in clinical trials (24%). Conclusions: OAC who receive ICI therapy frequently experience irAEs that may result in treatment interruption, discontinuation or long-lasting toxicity. Nurses are well positioned to provide support to this vulnerable population.

Research paper thumbnail of Immune Checkpoint Inhibitors in Lung Cancer and Melanoma

Seminars in Oncology Nursing

Research paper thumbnail of Understanding and Managing Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Patients With Advanced Melanoma

Journal of the Advanced Practitioner in Oncology, 2017

Research paper thumbnail of Checkpoint Inhibitors: Common Immune-Related Adverse Events and Their Management


Clinical Journal of Oncology Nursing