More Data Link Obesity to Better Survival for Cancer Patients on Immunotherapy

Another study, this time involving head and neck squamous cell carcinoma (HNSCC), has demonstrated a link between obesity and survival in cancer patients receiving immunotherapy.

In a propensity-score matched analysis of 166 HNSCC patients treated with a checkpoint inhibitor, which is now standard of care in the advanced setting, researchers reported improved overall survival (OS) at multiple time points among those with a BMI of 30 or above versus those with a normal BMI:

• 6 months: HR 0.54 (95% CI 0.31-0.96)
• 3 years: HR 0.56 (95% CI 0.38-0.83)
• 5 years: HR 0.62 (95% CI 0.44-0.86)

Obesity was also associated with improvements in functional outcomes, including decreased gastrostomy and tracheostomy tube dependence, with no differences in immune-related adverse events, according to Joseph Curry, MD, of Thomas Jefferson University Hospital in Philadelphia, and colleagues, who detailed their findings in JAMA Otolaryngology–Head & Neck Surgery.

Prior studies in melanoma, renal cell carcinoma, and other tumor types have shown links between higher BMIs and better survival for patients treated with checkpoint inhibitors, but reports in head and neck cancer specifically have been limited.

“Although greater nutritional reserve from excess adipose tissue may protect against wasting and death due to failure to thrive in oncologic treatment, previous investigations also delineate obesity’s key effects on the immune state that would suggest a more nuanced explanation for obesity’s favorable outcomes” with immune checkpoint inhibitors, they explained.

Curry’s group also pointed to a study suggesting that for patients with obesity, PD-1-mediated T-cell dysfunction resulted in cancers that were more responsive to anti-PD-1 checkpoint blockade, “thus revealing a potential immunologic explanation to the oncologic benefits of obesity observed in our study.”

On the improvements in functional outcomes, they pointed out that few studies have examined the impact of obesity on this surrogate measure of quality of life.

Their findings there demonstrated that obesity was not associated with a decreased odds of dysphagia when compared with a normal BMI (20-24.9), but it was associated with a significantly lower odds of gastrostomy and tracheostomy tube dependence, respectively, at multiple time points:

• 1 year: ORs of 0.41 (95% CI 0.21-0.78) and 0.52 (95% CI 0.28-0.90)
• 3 years: ORs of 0.35 (95% CI 0.18-0.65) and 0.45 (95% CI 0.24-0.90)
• 5 years: ORs of 0.34 (95% CI 0.18-0.65) and 0.45 (95% CI 0.24-0.90)

“Increased nutritional reserve in patients with obesity likely plays a greater role in gastrostomy tube dependence; however, tumor site is a notable confounder that is not directly addressed in this investigation,” the researchers noted. “Patients treated with systemic chemoradiotherapy, particularly those with recent weight loss, are at significantly higher risk of gastrostomy tube dependence months to years after treatment.”

For their population-based cohort study, Curry and colleagues used 2012-2023 data from the TriNetX Global Collaborative Network database, identifying patients with HNSCC who were treated with a checkpoint inhibitor — durvalumab (Imfinzi), nivolumab (Opdivo), ipilimumab (Yervoy), or pembrolizumab (Keytruda). In the U.S., only nivolumab and pembrolizumab are approved for HNSCC.

After propensity score-matching for pretreatment comorbidities and oncologic staging, the main analysis included 166 patients (83 with obesity and 83 with a normal BMI). Two-thirds were men, their average age was 63 years, and 75% were white, 13% were Black, and 12% were of unknown race.

The researchers also examined OS and functional outcomes among patients with overweight (BMI of 25-29.9) or who were underweight (BMI <20), but found no significant differences at any point compared with the normal-weight group.

Curry’s team cited a number of limitations to their findings, including the potential for inaccuracies in electronic health record documentation; the inability to capture all histological types of HNSCC or progression-free survival (PFS) in TriNetX, pointing out that obesity has previously been linked with improved PFS; and that patients’ indication for a checkpoint inhibitor was not clear (e.g., for advanced disease or in the neoadjuvant setting), but they said most likely it was for recurrent or metastatic disease where it’s standard of care.

Finally, BMI was only captured pretreatment and the study authors noted that “a common critique of BMI is that it is an inadequate measure of adiposity.”

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