High-Fat Breakfast May Improve Lung Cancer Treatment: Study

A 3D illustration of lung cancer. Shutterstock

A recent randomized crossover trial uncovered a potential breakthrough for patients with advanced non-small cell lung cancer (NSCLC). The study suggests that opting for a fuller breakfast, as opposed to a low-fat breakfast, may significantly increase the concentration of a key treatment, alectinib, in the blood. This promising finding may potentially translate into improved survival rates for NSCLC patients.

Alectinib is a small-molecule kinase inhibitor. Initially receiving accelerated approval from the U.S. Food and Drug Administration (FDA) in December 2015, the drug obtained regular approval in 2017 for treating anaplastic lymphoma kinase (ALK)-positive metastatic NSCLC. The drug was found to be safe and effective and has become a first-line treatment for this advanced form of lung cancer.

Breakfast Choice Boosts Drug Concentration

Published in the June 2023 issue of the Journal of the National Comprehensive Cancer Network (JNCCN), the study shed light on the importance of the timing of alectinib administration in relation to meals. Patients who consumed a continental breakfast or a self-chosen lunch along with their initial dose of alectinib demonstrated a 14 or 20 percent higher concentration of the drug in their blood, respectively, compared to those who had a low-fat breakfast.

The low-fat breakfast used in the trial included 250 grams of semi-skimmed (1.5 percent fat) yogurt and 250 milliliters of water. In comparison, the continental breakfast included two slices of wheat bread with butter and either ham, cheese, or peanut butter and 250 milliliters of semi-skimmed milk.

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All participants took the second dose with a self-chosen dinner, emphasizing the potential impact of breakfast and lunch on drug concentration.

Lead author and doctoral candidate Daan A.C. Lanser of the Department of Medical Oncology at Erasmus University Medical Center’s Erasmus Cancer Institute emphasized the significance of consuming alectinib with a substantial meal containing adequate fat for effective lung cancer treatment.

“This is important information for patients since we know that higher alectinib concentrations in blood could result in more efficacy of the drug, a longer treatment duration, and therefore, hopefully, a better survival,” Lanser said in a statement.

Supporting evidence from a pharmacokinetic report (pdf) issued by the FDA revealed that a significant reduction in tumor size occurred when alectinib concentrations reached a trough level of 435 ng/ml.

A clinical study conducted in 2020 confirmed the suggested exposure-response threshold, demonstrating that the effectiveness of alectinib treatment correlates with the drug’s concentration in the body. Patients who surpassed the threshold of alectinib trough level experienced a twofold increase in progression-free survival (PFS) compared to those with lower alectinib exposure. In contrast, the study found that patients who did not achieve the threshold exhibited a relatively poor PFS of only 12.6 months.

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A randomized controlled trial has been initiated to further explore the relationship between drug levels and patient survival, with ongoing recruitment of participants.

How Does Food Interact With the Cancer Drugs?

The JNCCN study authors highlighted that they observed higher exposure for other cancer drugs when administered with meals containing higher fat content. These drugs include pazopanib, approved for kidney cancer treatment; nilotinib, approved for leukemia treatment; and lapatinib, approved for breast cancer and other solid tumors.

In the case of alectinib, specifically, the researchers noted the potential of food, especially high-fat content, to enhance the dissolution and absorption of the drug in the gastrointestinal tract.

Alectinib, known for its poor gastrointestinal absorption, is significantly influenced by food intake. Consuming a high-fat meal resulted in a threefold increase in exposure compared to the fasted state.

However, “the precise relationship between food intake and the absorption of alectinib is currently unknown,” the authors noted. They further suggested that a fat-exposure relationship likely explains the increased exposure, as fat may enhance the solubility of lipophilic substances like alectinib.

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During the trial, the average fat content was 21.3 grams for the continental breakfast diet, 3.8 grams for the low-fat yogurt diet, and 19.5 grams for the self-chosen lunch diet. Notably, there was no significant difference in alectinib exposure between patients who took the drug with a continental breakfast and those with a self-chosen lunch.

A 2015 study with ceritinib, another kinase inhibitor used to treat NSCLC, showed similar pharmacokinetic effects. Ceritinib administered with a low-fat meal resulted in a 58 percent increase in exposure. Compared with fasted state, a high-fat meal resulted in a 73 percent increase in ceritinib exposure.

Study Limitations

The trial had a relatively small sample size of 23 participants, and three individuals dropped out for various reasons, such as switching therapy, personal factors, or having to undergo intestine surgery.

Another limitation is the lack of diversity in age and ethnicity, as all 20 patients were aged between 58 and 69, with 19 being Caucasian.

Regarding side effects, the researchers noted a low overall number and severity, with no significant differences observed among the three groups.

Some of the authors disclosed receiving grant or research support from alectinib’s manufacturer, the Roche Group. Additionally, some authors disclosed their role as consultants to the Roche Group or other pharmaceutical companies.