A new study from Australian researchers has affirmed an unusual, almost paradoxical, observation that cancer patients with high body mass index (BMI) tend to display greater survival rates than patients with average healthy weights. The new study particularly focused on a large cohort of non-small-cell lung cancer (NSCLC) patients receiving a new form of immunotherapy treatment.
“Previous studies have explored a concept called as ‘obesity paradox’ where obesity is associated with increased risks for developing certain cancers and, counter-intuitively, may protect and give greater survival benefits in certain individuals,” explains lead investigator on the study Ganessan Kichenadasse.
This obesity paradox has been a source of great debate among scientists in recent years. Many researchers claim this observed association, suggesting obesity can sometime be protective, is simply a correctional anomaly underpinned by unmeasured factors in epidemiological studies. A landmark study from UC Davis last year offered a bold new hypothesis to explain the obesity paradox, at least in some cases concerning a specific cancer treatment.
A new class of immunotherapy drugs called checkpoint inhibitors work by blocking activation of a protein called PD-1, a molecule that stifles the ability of immune T-cells to hunt, and kill, cancer cells. The UC Davis study suggested obese patients present higher volumes of PD-1, which subsequently makes the checkpoint inhibitor drugs more effective as they stimulate greater T-cell activity.
The new study from Australia’s Flinders University doesn’t explicitly verify this hypothesized mechanism, but it does offer new evidence supporting the link between obesity and increased immunotherapy efficacy in one of the largest cohorts studied to date.
The research examined nearly 1500 patients with non-small-cell lung cancer (NSCLC) receiving a new checkpoint inhibitor treatment known as atezolizumab. The study notes a strong relationship between higher BMI and improved responsiveness to the immunotherapy treatment.
A smaller cohort with NSCLC being treated with a more traditional chemotherapy agent called docetaxel was also studied. That cohort did not show the same correlation between high BMI and treatment efficacy, suggesting the link between obesity and efficacy is specific to this form of immunotherapy.
“Our study provides new evidence to support the hypothesis that high BMI and obesity may be associated with response to immunotherapy,” says Kichenadasse. “While our study only looked at baseline and during treatment, we believe it warrants more studies into the potentially protective role of high BMI in other cancer treatments.”
None of these results at all suggest cancer patients should be gaining weight before undergoing immunotherapy treatments, and obesity is still a certain risk factor in developing a large number of cancers. However, this study does offer clinicians a better understanding into why some patients may not respond as well as others to new checkpoint inhibitor treatments. The research also suggests BMI should be taken into account when selecting patients for future immunotherapy trials.
The study was published in the journal JAMA Oncology.
Source: Flinders University via Scimex
