Overweight or obese patients may take longer to respond and be less responsive to immune checkpoint inhibitors in non-small cell lung cancer: A retrospective review.

Abstract

e21209 Background: Immune checkpoint inhibitors (ICI) are now the standard of care in the treatment of non-small cell lung cancer (NSCLC). ICIs may be used as monotherapy or in combination with chemotherapy. Increased recruitment of inflammatory cells in the tumor micro-environment is associated with a poor response to ICIs. Although obesity is a risk factor for many types of cancers, including lung cancer, it is associated with a low systemic inflammation state. This creates an effect known as the “obesity paradox,” resulting in better treatment-related outcomes in overweight and obese patients receiving ICIs. However, in obese patients, the neutralizing interleukin (IL) - 1β level is high, which can decrease the responsiveness to ICI. We aim to study the effect of increased weight on treatment-related outcomes in NSCLC patients receiving ICI. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs, such as pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab, alone or in combination with chemotherapy. Overweight was defined as having a BMI of 25 – 29.9 while obesity was defined as having a BMI of ≥ 30. Overall survival (OS), progression free survival (PFS), best radiographic response, and the time to achieve radiographic response were evaluated. Cox regression univariate and multivariate analyses were performed. Logistic regression and Chi-square tests were applied. Results: Of the 178 patients with NSCLC, 81% had adenocarcinoma, and 19% had squamous, adenosquamous, or large cell carcinoma. The majority of patients were female (56.2% vs. 43.8%). Overall, 48.6% patients were overweight or obese. The objective response rate (ORR) was 45.1% and the disease control rate (DCR) was 75.8%. The ORR was 37% in overweight/obese patients compared to 52% in patients with a normal weight (p = 0.06). The DCR was 76% vs. 73.9%, (p = 0.7). The median time to achieve the best radiographic response was 3.7 months in overweight/obese patients compared to 2.5 months in those of normal weight (p = 0.2). A considerably higher proportion of the patients progressed in overweight/obese category (80.7% vs. 69.3%, P = 0.08). However, there was no significant difference in median PFS between the two categories (7.4 vs. 8.1 months, P = 0.2). The overall survival was not significant different between both categories (15.9 vs. 16.8 months, P = 0.5). Conclusions: Our study suggests that obesity and overweight status can result in a low response rate to ICIs in NSCLC patients and can delay the time to achieve the best radiographic response per RECIST criteria. However, we did not observe any significant impact on the overall or progression-free survival. A large, population-based study will help to elucidate the impact of weight on the responsiveness to ICI.