Updated guidelines1 recommend that patients with cancer and obesity receive the full approved doses of immunotherapy and targeted therapies, but do oncologists agree with this approach?
In the past, many oncologists routinely underdosed chemotherapy in patients with obesity and cancer due to concerns about excess toxicity. However, studies have shown that patients with obesity tend to experience less toxicity than other patients, and underdosing chemotherapy can negatively impact survival outcomes.2
As a result, in 2012, the American Society of Clinical Oncology (ASCO) released guidelines recommending against underdosing chemotherapy in patients with obesity and cancer, stating that “full, weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer.”3
Now, in updated guidelines, ASCO is recommending an analogous dosing strategy for immunotherapy and targeted therapies in patients with cancer and obesity.1
To develop the updated recommendations, the guideline authors reviewed 60 studies published from November 1, 2010, to March 27, 2020. Their analysis spanned retrospective and prospective cohort studies, meta-analyses of observational studies, and post hoc analyses of randomized controlled trials.
The authors’ findings support ASCO’s previous recommendation to administer full, weight-based doses of cytotoxic chemotherapy to patients with obesity and cancer.
The findings also support the new recommendation that prescribing information provided by the U.S. Food and Drug Administration (FDA) should be used uniformly for patients with and without obesity when it comes to dosing of checkpoint inhibitors and targeted therapies.
“These guidelines are basically to say that FDA-approved prescribing information for all these new agents, just like the original cytotoxic, should be used in patients with cancer, regardless of whether the patient is overweight, obese, or a healthy weight,” said Gary Lyman, MD, MPH, a medical oncologist and the senior lead of health care quality and policy at the Hutchinson Institute for Cancer Outcomes Research in Seattle, Washington, who coauthored the ASCO guideline update.
Moreover, if a dose should be reduced in response to high-grade toxicity, the same reduction guidelines should be applied to all patients, whether they are obese or not.
“In other words, there should be no unique dose modification because the patient is obese or overweight,” Dr Lyman said.
In another addition to the guidelines, the authors concluded that any of the standard formulas used to measure body surface area are fine to use, and there is no one formula that is superior to another.
The Consequences of Underdosing
Coral Omene, MD, PhD, expressed support for ASCO’s new dosing recommendations for immunotherapy and targeted therapies, stating that they align with how she and her colleagues have already been practicing. Dr Omene is a medical oncologist at Rutgers Cancer Institute of New Jersey in New Brunswick, and she was not involved in the guideline update.
“I think we have more and more data that suggest that we should maintain the same doses for both normal-weight and obese patients,” Dr Omene said.
She noted that, before ASCO introduced the original recommendation for chemotherapy dosing in 2012, oncologists would routinely cap doses in patients with obesity. That strategy ended up backfiring because it reduced the effectiveness of chemotherapy in these patients and affected their outcomes.
Underdosing had particularly dramatic consequences for Black patients, a group in which obesity is highly prevalent, Dr Omene said. For example, researchers found that Black women with breast cancer tended to receive lower doses of adjuvant chemotherapy than White women.4 Meanwhile, other research suggested that such reductions led to worse survival outcomes.5
“So I think we know enough [to support] that underdosing or capping doses would actually affect the patient negatively,” Dr Omene said.
She added that she hopes this new update will encourage any oncologists who are underdosing novel cancer therapies to stop that practice.
“Hopefully, this ASCO guideline will help inform those oncologists and help to bolster the culture of not capping doses,” Dr Omene said.
She also pointed to a need for studies that would examine effects of the new guidelines on patient outcomes. “And, hopefully, we will see that maybe patients were doing better because they were getting proper dosing,” she said.