Cancer-related diarrhea often leads to treatment discontinuation
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Patients with cancer-related diarrhea appeared 40% more likely than those without the condition to discontinue index therapy, according to retrospective study results presented during the virtual ASCO Annual Meeting.
Cancer-related diarrhea also prompted earlier switches to alternate regimens and additional health care utilization, results showed.
“Cancer-related diarrhea is a very common and underappreciated problem, [and] current strategies to manage and control [this adverse effect] are suboptimal,” Pablo C. Okhuysen, MD, FACP, professor in the department of infectious diseases, infection control and employee health at The University of Texas MD Anderson Cancer Center, told Healio. “There is an urgent need to develop and study novel agents that can control and treat diarrhea [among patients with cancer] receiving chemotherapy and targeted therapies so patients can continue with the best possible cancer regimen.”
Nearly half of patients with cancer develop diarrhea during treatment, and rates can reach 80% when certain chemotherapy agents are used, according to NCI statistics. This potentially debilitating condition also can be due to immunotherapy, targeted therapy, surgery, infection or other factors.
Management typically includes an evaluation to identify modifiable or treatable causes — such as Clostridium difficile infection — and strategies for symptom control, such as dietary interventions to maintain hydration, ease digestion and avoid irritants.
“Antimotility agents such as loperamide and opiates have been the cornerstone for treatment,” Okhuysen said. “However, these agents are associated with side effects on their own, such as constipation, bloating and — in high doses — central nervous system toxicity.
“Despite these measures, diarrhea cannot be controlled in a large number of patients,” Okhuysen added. “Because of the lack of newer agents, both physicians and patients have ‘learned to live’ with this bothersome symptom and accept diarrhea as part of the standard of care or switch to a second-line regimen to avoid diarrhea.”
Okhuysen and colleagues performed a longitudinal observational study to estimate the prevalence of cancer-related diarrhea and assess the effect of the condition on treatment patterns such as adherence, persistence, discontinuation, dosing and switching of chemotherapy or targeted therapies.
“Our study design tried to include all patients with cancer and diarrhea,” Okhuysen said. “This meant we included some patients [who] were already experiencing diarrhea at the time of cancer diagnosis, as well as those [who] developed diarrhea after cancer diagnosis.”
Researchers used diagnosis codes or pharmacy claims from the IQVIA PharMetrics Plus database to identify adults aged 18 to 65 years with cancer-related diarrhea. These individuals were matched 1:1 with patients who did not have cancer-related diarrhea.
Investigators established the index date as the date of first cancer claim — either diagnosis or treatment — and re-indexed patients based on their first cancer-related diarrhea claim. Each patient had a 6-month pre-index period, as well as minimum 3-month follow-up post-index period. Patients with cancer-related diarrhea also were required to have 12 months’ continuous enrollment after their re-index date.
Okhuysen and colleagues evaluated treatment patterns for first cancer therapy — chemotherapy alone vs. targeted therapy alone vs. a combination of the two modalities — for all patients.
They defined treatment discontinuation as a 30-day gap from index therapy for those receiving chemotherapy and a 14-day gap from index therapy for those receiving targeted therapy. Those who started a new chemotherapy or targeted therapy prescription within 30 days after discontinuation of index therapy were determined to have switched therapies.
Researchers defined adherence as proportion of days covered in the 12-month post-index period, and they defined persistence as mean number of days on index therapy.
Researchers determined cancer-related diarrhea affects approximately 0.25% of the U.S. population.
The matched analysis included 208,270 patients with solid tumors or hematologic malignancies, all of whom had survived at least a year after diagnosis. Half (n = 104,135) had cancer-related diarrhea and half did not.
In each cohort, 47,220 patients received chemotherapy alone as index therapy, 5,313 patients received chemotherapy and targeted therapy, and 2,427 received targeted therapy alone. The remainder received other therapy or no therapy.
Results showed patients with cancer-related diarrhea more frequently discontinued index therapy (82.4% vs. 64.6%; P < .0001). The trend persisted regardless of treatment type (chemotherapy, 81.5% vs. 62.3%; targeted therapy, 69.2% vs. 64.3%; both, 96% vs. 85.5%; P < .0001).
Results of multivariate modeling that controlled for potential confounding variables showed a 40% elevated risk for index therapy discontinuation among patients with cancer-related diarrhea.
“We knew from our own practices that cancer-related diarrhea impacts the ability of patients to remain on cancer therapy,” Okhuysen told Healio. “We did not anticipate that the impact would be this large.”
Researchers also reported higher rates of therapy switch (19.4% vs. 8.3%; P < .0001) and augmentation (10.1% vs. 9.4%; P = .0001), as well as lower rates of treatment persistence (17.6% vs. 35.4%; P < .0001), in the cohort with cancer-related diarrhea.
Mean time to index therapy discontinuation (59.6 ± 54.1 days vs. 68.3 ± 76.6 days), mean time to therapy switch (72 ± 48.6 days vs. 96.9 ± 84 days), mean persistence (95.1 ± 98.1 days vs. 154.3 ± 142.7 days) and mean adherence (25.5% ± 37.2 vs. 47.9% ± 41) were significantly lower among patients with cancer-related diarrhea (P < .0001 for all).
Results also showed significantly higher all-cause health care resource utilization among patients with cancer-related diarrhea, including ER visits (36.2% vs. 18.9%), lab/pathology services (99.3% vs. 94.9%), radiology services (92.8% vs. 80.3%), surgical services (89.8% vs. 66.3%), outpatient ancillary services (99.3% vs. 92.4%) and inpatient visits (29.6% vs. 12.8%; P < .0001 for all).
Cox multivariate analysis showed patients with cancer-related diarrhea who received chemotherapy and targeted therapy had higher health care resource utilization and health care costs than patients in the other therapy cohorts.
The analysis did not include a comparison of survival outcomes among patients who developed cancer-related diarrhea and those who did not.
“This is one of the limitations in our study,” Okhuysen said. “This is a survivors study. Because we were interested in determining the impact on discontinuation and adherence to cancer therapy, the study design included patients [who] survived at least 12 months after cancer diagnosis. This precluded us from examining mortality in both groups of patients.
“Another limitation is that diarrhea was evaluated as a risk factor in isolation and did not include other organ toxicities or factors that co-occurred with diarrhea that could have also required cancer treatment alterations,” Okhuysen added. “Cancer-related diarrhea likely also impacts mortality [because] it is frequently associated with dehydration, acute kidney injury, electrolyte imbalance and malnutrition. ... As cancer therapies continue to evolve and grow, we need additional ‘real-world’ studies that examine the impact they have in causing cancer-related diarrhea.”
References:
NCI. Gastrointestinal complications (PDQ)-Health Professional Version. Available at: www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all. Accessed June 2, 2021.
Okhuysen PC, et al. Abstract 12111. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
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Okhuysen PC, et al. Abstract 12111. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
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