Most research has revealed that being overweight, defined as having a BMI greater than 25 kg/m2, has become the second most important cancer risk factor. Overweight people are more likely to develop diseases such as colon cancer, pancreatic cancer, and others. It is, however, a potentially modifiable risk factor, as the incidence of cancer can be lowered by controlling weight (14). Prospective cohort research confirmed that having a high BMI was related to worse prognosis of breast cancer (15). However, other studies have found that, compared to patients with normal BMI, the underweight had a lower survival rate, while those who were obese had a higher survival rate. For Asian colorectal cancer patients, a BMI cut-off value of 20.44 kg/m2 is a relevant indicator (16). As a result, the prognostic value of BMI varies amongst cancers. Some research in recent years has found a link between BMI and pharmacological efficacy. Patients with a BMI of < 18.5 kg/m2 may not benefit from induction chemotherapy for locally advanced nasopharyngeal cancer (17). It was discovered that lowering BMI before treatment was associated with worse ORR (p = 0.01) and DCR (p = 0.01) in a sample of patients with multiple advanced stage cancers who received immunotherapy (18).
Our study discovered no significant difference in ORR between the underweight, normal-weight, and overweight groups, even though the overweight and normal-weight groups were significantly and statistically better than the underweight group (62.9%, 61.5%, and 33.3%, p = 0.086). It should be noted that the benefits of ORR were more noticeable in patients of normal and overweight weight. It also followed the same pattern as DCR (p = 0.034). Another retrospective research of various malignancies discovered that ORR was considerably higher in overweight/obese patients treated with ICIs than in non-overweight patients (p < 0.0001) (19). In clinical studies of patients with gynecological malignant tumors, it was found that patients with BMI < 25 kg/m2 before treatment increased the median target lesion area by 33.8% (1.33 [14.5–62.9]) after four cycles of treatment with pembrolizumab, while the median target lesion area decreased by 30.5% (0.70 [0.44–1.21]) in patients with BMI ≥ 25 kg/m2 (20). As a result, pre-treatment BMI appears to be a promising biomarker that may help us identify individuals who benefit most from ICIs treatment. Additionally, our research established that it is feasible in patients with advanced lung cancer.
Additionally, previous research has established a relationship between BMI and the prognosis of cancer patients treated with ICIs, with obese individuals having a better prognosis. After immune checkpoint blockade (ICB) treatment, obese patients (BMI ≥ 30 kg/m2) had a better OS than overweight patients (BMI: 18.5–24.9 kg/m2) (HR: 0.67, 95% CI: 0.57–0.78, p < 0.01). After ICB treatment, the OS of overweight patients was considerably better than that of normal-weight patients (HR: 0.81, 95% CI: 0.71–0.93, p < 0.01). After ICB treatment, PFS of obese patients was likewise significantly longer than that of overweight patients (p < 0.01) or normal-weight patients (p < 0.01) (21). Compared to Europeans, overweight persons are uncommon in China (22). Our investigation discovered a link between pre-treatment BMI and disease outcome in individuals with advanced lung cancer receiving immunotherapy alone or combined with chemotherapy. Not only did patients with a BMI ≥ 25 kg/m2 have the best PFS, but even those with a normal weight had a superior PFS than those with an underweight BMI (p = 0.006). Another study found a significant correlation between a high BMI with PFS and OS in 962 patients with PD-L1-positive NSCLC treated with pembrolizumab (12). However, in a trial with metastatic melanoma, BMI had a different prognostic value than treatment. BMI did not affect DCR, PFS, or OS in patients with metastatic melanoma treated with ICIs (23). Another study discovered that obesity was related to increased survival in patients with metastatic melanoma than those with a normal BMI (24). Although BMI has a varied prognostic value in solid tumors treated with immunotherapy, most studies in advanced lung cancer have demonstrated a correlation between BMI and prognosis in patients receiving immunotherapy alone or in combination. Our analysis corroborated this finding.
In general, increased emphasis has been paid to the occurrence of irAEs in patients receiving ICIs during treatment. Numerous studies have examined the relationship between BMI and treatment-related toxicity. In one study, patients who were overweight or obese were considerably more likely to suffer irAEs (of any grade) than patients who were normal weight (p < 0.0001) (19). In another study, overweight and obesity were predictors of irAEs in any grade when analyzed by univariate and multivariate analysis. Obesity was the sole predictor associated with an increased incidence of grade 3–4 irAEs (OR 11.9 [95% CI: 6.4–22.3]; p < 0.0001) (25). According to a publication, increased BMI is a significant predictor of irAEs (p = 0.016) in patients with NSCLC treated with anti-PD-1 or anti-PD-L1 inhibitors [13]. However, the incidence of irAEs among patients treated with anti-PD-1 and PD-L1 was superimposable regardless of BMI category (incidence of all grades irAEs: 31% for normal weight, 33% for overweight, and 36% for obese patients) (24). In our investigation, the incidence of irAEs was substantially greater in the underweight group than in the normal-weight and overweight groups (p = 0.016). This can show that BMI is connected with irAEs, or that underweight people have a worse physique and are more susceptible to acquiring irAEs. After all, our study included a modest sample size, so additional research is required to confirm the association between BMI and irAEs in advanced lung cancer patients receiving immunotherapy.
This study, to be sure, has some drawbacks. The study’s fundamental weaknesses include the small sample size and the retrospective nature of the analysis, and there were few selection biases, such as clinical trial subgroup data. Furthermore, we did not conduct OS analysis.
In conclusion, our findings indicate that pre-treatment BMI is a promising clinical biomarker for predicting ICIs therapeutic response and prognosis in patients with advanced lung cancer. Meanwhile, in patients with advanced lung cancer receiving ICIs, a BMI of 18.5 < kg/m2 is related to a greater rate of irAEs. However, due to the limitations of our study, additional research is required to confirm these findings and investigate their consequences.