Resting energy expenditure as a predictor of immune checkpoint inhibitors response in older patients with non-small cell metastatic lung cancer: A pooled analysis of two prospective cohort studies.

[BACKGROUND & AIMS] Immune checkpoint inhibitors (ICI) monotherapy is a frequent treatment for metastatic non-small cell lung cancer (mNSCLC) in the older patients. Reliable biomarkers predicting efficacy are needed to optimize treatment decision-making in this heterogeneous population. We investigated the relationship between basal metabolism and ICI outcomes in older patients with mNSCLC.

[METHODS] We enrolled 173 consecutive patients in this cohort study, of which 86 were over 70 years old (yo), attending a multidisciplinary risk assessment program which could include a geriatric assessment. All patients underwent measurement of resting energy expenditure (REE) by indirect calorimetry and theoretical REE (tREE) was estimated using the Harris and Benedict equation. Hypermetabolism was defined as mREE/tREE ≥110%. The main ICI efficacy outcome was the rate of progression at 6 months (P6M). Secondary outcomes were best response to ICI, progression-free survival (PFS) and overall survival (OS).

[RESULTS] The proportion of hypermetabolism in older patients was 49%. Hypermetabolism was not associated with geriatric assessment conclusions. Among older patients, 34% experienced partial- (PR) or complete-response (CR), 20% stable disease (SD) and 46% progressive disease (PD). Hypermetabolism was associated with an increase in P6M in hypermetabolic patients both under 70 yo (OR 5.6; 95%CI 2.31-13.52; p < 0.001) and over 70 yo (OR 3.6; 95%CI 1.59-8.13; p = 0.002) and was associated with worse OS (OR 2; 95%CI 1.33-3.02; p < 0.001).

[CONCLUSIONS] This study confirms that basal metabolism measured by indirect calorimetry is a host-dependent predictive biomarker of response to ICI in mNSCLC and as a prognostic factor even in older patients over 70 years of age.