Weight Gain Measurements May Be Underreported in ALK+ NSCLC Trials

Among patients with advanced anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) who were treated with Alecensa (alectinib), weight gain was underreported as a side effect, and actual weights showed a 10% or more increase in weight in 18% of patients.

Researchers, in study findings published in the Journal of Clinical Oncology, wrote that “our study highlights a huge discrepancy between the investigator-reported [side effect] weight gain and actual weight gain during the initial year of [Alecensa] treatment in the three clinical trials,” study authors wrote.

Actual weight gain in patients, regardless of severity, was substantially higher than reported side effect rates. Weight gain of any rate was significantly higher than reported side effect rates — 49% actual weight gain versus 5% recorded.

Time on Alecensa was positively associated with weight change, with an average increase of 4.4% over one year. Baseline body mass index (BMI) was not associated with weight change in J-ALEX and ALUR/ML29453 studies. Baseline albumin was positively associated with weight change in ALUR/ML29453, but it was not considered a clinically meaningful predictor.

Follow-up weights were recorded in the first year for three trials (J-ALEX, ALUR and ML29453) but were not recorded for the ALEX trial, study authors noted. In all, 2,622 weights were recorded from 302 subjects. At baseline, 13.6% of the Japanese population was underweight, compared to 5% of the Western population.

“These findings underscore the importance of raising awareness among physicians regarding the [side effect] weight gain, since obesity is a gateway to over 200 other diseases in both the short and long-term, which can significantly negatively affect quality of life, as well as mental and physical health,” study authors wrote. “Therefore, patients should be counseled before initiating treatment.”

Study authors emphasized the clinical relevance of weight gain when assessing the impact of significant weight increase on patients' quality of life and morbidity. However, they were unable to determine clinically significant baseline characteristics to identify patients at risk for Alecensa-induced weight gain, posing a challenge for weight gain prevention.

Despite this, study authors were able to substantiate that both Alecensa therapy and time on treatment are predictors of weight gain.

Given the significant impact of Alecensa-induced weight gain and the long-term survival of patients, preventative measures and targeted interventions are needed, according to study authors. This need is amplified by the emergence of adjuvant Alecensa for resected ALK+ NSCLC.

Currently, no specific dietary, lifestyle or medical recommendations exist for this population. Existing guidelines primarily focus on patients at risk for cardiovascular disease, a group that differs in characteristics and age distribution from those with ALK+ NSCLC. The authors recently considered the use of approved obesity medications —semaglutide, liraglutide, naltrexone/bupropion and orlistat — to address severe Alecensa-induced weight gain.

Alecensa therapy lasted a median of 139 days in the ML29453 trial, which was shorter than the other trials. At year one, only 4% (5 of 125) of patients in the ML29453 trial continued Alecensa, compared to 40.8% (42 of 103) and 45.9% (34 of 74) in the other trials. The ML29453 trial was terminated early by the sponsor due to Alecensa becoming available as standard treatment.

Reference:

“Body Weight Gain Associated With Alectinib in Patients With ALK1 Non–Small Cell Lung Cancer: Pooled Analysis of Individual Patient Data From Four Prospective Clinical Trials,” By Dr. Barend J. Sikkema, et al. Journal of Clinical Oncology.

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