Growing data linking obesity with improved survival in cancer patients receiving immunotherapy

Another study in head and neck squamous cell carcinoma (HNSCC) demonstrated an association between obesity and survival in cancer patients receiving immunotherapy.

In a propensity score-matched analysis of 166 patients with head and neck squamous cell carcinoma treated with checkpoint inhibitors, a standard of care for advanced disease, researchers reported improved overall survival (OS) at multiple time points in patients with a BMI of 30 or greater compared with patients 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 improved functional outcomes, including less dependency on gastrostomy and tracheostomy tubes, but there was no difference in immune-related adverse events, report Joseph Curry, MD, of Thomas Jefferson University Hospital in Philadelphia, and his colleagues. JAMA Otolaryngology-Head and Neck Surgery.

Previous research Malignant melanoma, Renal cell carcinomaand Other Tumor Types A higher BMI has been associated with improved survival in patients treated with checkpoint inhibitors, but reports specific to head and neck cancer are limited.

“While increased nutrient stores from excess adipose tissue may prevent debilitation and death due to growth deficiency during tumor therapy, previous studies have also revealed important effects of obesity on immune status, suggesting a more nuanced explanation for the favorable outcomes of obesity with immune checkpoint inhibitors,” the researchers explained.

Curry's group also pointed to research suggesting that in obese patients, dysfunction of T cells through PD-1 leads to cancer. Highly responsive to anti-PD-1 Checkpoint inhibition “uncovers a potential immunological explanation for the oncological benefit of obesity observed in our study.”

With regard to improving functional outcomes, they noted that few studies have investigated the effect of obesity on this surrogate indicator of quality of life.

Results showed that obesity was not associated with a reduced odds of dysphagia when compared with normal BMI (20-24.9), but was associated with significantly reduced odds of gastrostomy and tracheostomy tube dependence at multiple time points.

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

“Although increased nutritional reserves in obese patients likely play a major role in gastrostomy tube dependency, tumor site is an important confounding factor not directly addressed in this study,” the researchers note. “Patients who received total body chemoradiation therapy, especially those who have recently lost weight, are at significantly higher risk for gastrostomy tube dependency even months to years after treatment.”

For their population-based cohort study, Curry and colleagues used data from 2012 to 2023 from the TriNetX Global Collaborative Network database and compared the efficacy and safety of the checkpoint inhibitors durvalumab (Imfinzi), nivolumab (Opdivo), ipilimumab (Yervoy), or Pembrolizumab (Keytruda). In the United States, only nivolumab and pembrolizumab are approved for head and neck squamous cell carcinoma.

After propensity score matching for pretreatment comorbidities and tumor staging, 166 patients (83 obese and 83 normal BMI) were included in the main analysis: two-thirds were men, mean age was 63 years, 75% were white, 13% were black, and 12% were of unknown race.

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

Curry's team cited several limitations to their findings, including potential inaccuracies in electronic medical record documentation, TriNetX's inability to capture all histological types or progression-free survival (PFS) in head and neck squamous cell carcinoma (noting that obesity has previously been associated with improved PFS), and the lack of clarity regarding patient indications for checkpoint inhibitors (for example, in advanced disease or the neoadjuvant setting), which they said are likely standard of care in cases of recurrent or metastatic disease.

Finally, BMI was measured only before treatment, and the study authors note that “a common criticism of BMI is that it is an inadequate measure of obesity.”