High BMI Tied to Improved OS With Immune Checkpoint Inhibition in Advanced NSCLC

Findings from a pooled analysis of 4 clinical trials showed a link between high body mass index (BMI) and improved overall survival (OS) in patients with advanced non–small-cell lung cancer (NSCLC) treated with atezolizumab (JAMA Oncol. 2019 Dec 26. Epub ahead of print).

“High body mass index (BMI) is independently associated with overall survival benefit from immune checkpoint inhibitor therapy in patients with melanoma, yet whether BMI is associated with outcomes in patients with advanced non–small cell lung cancer treated with atezolizumab remains unknown,” said Ganessan Kichenadasse, MBBS, FRACP, College of Medicine and Public Health, Department of Clinical Pharmacology, Flinders University, Bedford Park, South Australia, and co-investigators.

Thus, Dr Kichenadasse et al sought to evaluate whether a connection exists between BMI and survival outcomes and adverse events in patients with NSCLC given atezolizumab therapy by conducting a pooled analysis of data from 4 international, multi-center clinical trials.

These trials included 2 single-arm studies, BIRCH and FIR (data cutoffs, May 28, 2015 and January 7, 2015, respectively), and 2 randomized, 2-arm studies, POPLAR and OAK (data cutoffs, May 8, 2015 and July 7, 2016, respectively).

Patients with advanced NSCLC were selected for inclusion in these studies if they were previously untreated or treated with at least 1 line of systemic therapy and had measurable disease and good organ function without contraindications for chemotherapy or immune checkpoint inhibitor therapy.

Data were analyzed between February 28, 2019, and September 30, 2019, and the main end point of the study was the association between BMI and OS, progression-free survival (PFS), and treatment-related adverse events.

Across all 4 studies, adequate data were available for 2110 patients, including 1434 patients (median age, 64 years) given atezolizumab and 676 patients (median age, 63 years) given docetaxel.

A linear link between increasing BMI and OS was observed in patients who received atezolizumab. In addition, after adjusting for confounding variables, the investigators found an association between obesity (BMI ≥30) and significantly improved OS in recipients of atezolizumab, but not in those given docetaxel.

Of note, the link between BMI and OS/PFS was strongest in the subgroup of patients with high PD-L1 expression.

Among patients with the highest category of PD-L1 expression (≥50% of tumor cells or ≥10% of tumor-infiltrating immune cells; n = 436), rates of OS had hazard ratios of 0.36 (95% CI, 0.21-0.62) among obese patients and 0.69 (95% CI, 0.48-0.98) among overweight patients. These patients had PFS hazard ratios of 0.68 (95% CI, 0.49-0.94) and 0.72 (95% CI, 0.56-0.92), respectively.

There was no link found between treatment-related adverse events and BMI.

“High BMI appears to be independently associated with improved survival with atezolizumab in patients with NSCLC, raising the possibility that baseline BMI should be considered as a stratification factor in future immune checkpoint inhibitor therapy trials,” Dr Kichenadasse and colleagues concluded.—Hina Porcelli