ASCO has approved new recommendations for the appropriate dosing of systemic anticancer agents in adults with obesity and cancer.1 The guideline update was based on evidence collected from a systematic review of the literature published between November 1, 2010, and March 27, 2020, regarding dosing of chemotherapy, immunotherapy, and targeted therapies in obese adults with cancer. The original guideline published in 2012 focused on chemotherapy agents alone.2
“The motivation behind this guideline update was to incorporate new data about the impact of dose in obese individuals with cancer, the benefit of full weight-based dosing, and any evidence regarding the noncytotoxic agents, such as immunotherapy and targeted therapy,” said Guideline Co-Chair Jennifer Griggs, MD, MPH, FASCO, of the University of Michigan. “We also aimed to close any gaps since the last guideline and to update the literature.”
Jennifer Griggs, MD, MPH, FASCO
Gary H. Lyman, MD, MPH, FASCO, FRCP
Evaluating Dosing Recommendations for New Agents
Gary H. Lyman, MD, MPH, FASCO, FRCP, of the Fred Hutchinson Cancer Research Center and Guideline Co-Chair, explained that there has always been a concern about potential toxicity of chemotherapy agents in overweight or obese patients.
“Dosing of cancer therapies is often based on the body surface area—a composite of the patient’s height and weight—so the heavier the patients, the greater the amount of drug they receive,” he said. “Traditionally, there was often a cap that was placed on the dose…. However, studies have shown that capping of the chemotherapy dose may result in underdosing of patients who are obese.”
Based on available evidence, in 2012 the ASCO expert panel recommended that overweight and obese patients receive the actual calculated dose, regardless of their weight. However, since then, many new agents have been approved for use in patients with cancer, including tyrosine kinase inhibitors, targeted monoclonal antibodies, and, more recently, immunotherapies.
“All of these are quite different than the traditional chemotherapies, and the dosing for many of them is not as closely tied to weight or body surface area,” Dr. Lyman said. “So, we thought it was important to provide an update that includes these newer therapies.”
Reinforcing Full Weight-Based
Dosing Recommendations
This latest update addresses six clinical questions in adult obese patients with cancer, specifically, those regarding:
- The safety and efficacy of full, weight-based dosing of cytotoxic chemotherapy;
- The use of fixed-dose cytotoxic chemotherapy;
- The safety and efficacy of approved doses of checkpoint inhibitors (fixed or weight-based);
- The safety and efficacy of approved doses of targeted therapies (fixed or weight-based);
- Modification to systemic antineoplastic therapy doses or schedules in case of high-grade toxicity; and
- The best way to calculate body surface area.
Based on the review of evidence from 60 studies that met eligibility criteria, the expert panel recommended the following:
- Full weight-based dosing of chemotherapy, irrespective of obesity status;
- The use of fixed dosing of chemotherapy only for specific cytotoxic agents approved by the U.S. Food and Drug Administration (FDA; eg, bleomycin);
- The use of FDA-approved prescribing information for immune checkpoint inhibitors in all patients, irrespective of obesity status;
- The use of FDA-approved prescribing information for targeted therapies in all patients, irrespective of obesity status;
- Dose reduction of systemic antineoplastic therapy based on already established guidelines for dose reduction for all patients, irrespective of obesity status; and
- The use of any standard formula to calculate body surface area.
“The key takeaway is that we do not have any evidence of excess toxicity when actual body weight is used to determine doses,” Dr. Griggs said. “We are recommending, based on what we know now, that dose limits are not supported by the evidence. In the absence of pharmacokinetic and pharmacodynamic data, we can’t talk about additional personalization.”
A Step Closer to Achieving Equity in Cancer Care
Both Guideline Co-Chairs are optimistic that these latest recommendations will bring about improvements in care, especially in those populations that are already at greater risk of suboptimal outcomes.
“I think that the greatest improvement will be among patients who are cared for in practices that continue to be concerned about the original guidelines,” Dr. Griggs said. “Now that we’re reinforcing the guideline with an update, that should give oncologists the support they need. We do expect to see an improvement in outcomes, including overall survival and disease-specific survival, if there is still a gap in dose selection.”
She also noted that members of minority groups and other marginalized patients with cancer are more likely to have higher body size and that the full body weight dosing is a step closer to achieving equity in their care.
Dr. Lyman emphasized the practice-changing impact that the original guideline had across many large cancer centers and cancer cooperative groups. “Time will tell whether this update will have a similar impact on the dosing of newer cancer therapies in clinical practice, guideline recommendations, and forthcoming clinical trials,” he said.
Both the original 2012 guideline and the 2021 guideline update reinforce and build upon important recommended care for systemic therapy doses in heavier or obese adult patients with cancer. The ASCO expert panel recommend that this patient population should receive standardized and guideline-recommended care to reduce unwanted, and potentially harmful, variations in dosing that may occur across different practice settings.
REFERENCES
1. Griggs JJ, Bohlke K, Balaban EP, et al: Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol 39:2037-2048, 2021.
2. Griggs JJ, Mangu PB, Anderson H, et al: Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 30:1553-1561, 2012.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, May 5, 2021. All rights reserved.
