Can sintilimab maintain or improve HRQoL in 1L treatment of NSCLC?

Addition of sintilimab to pemetrexed and platinum-based chemotherapy maintained or improved health-related quality of life (HRQoL) and symptoms compared with chemotherapy alone in first-line (1L) treatment of locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC), according to a prespecified exploratory analysis of the phase III ORIENT-11 trial.

The addition of sintilimab to pemetrexed-platinum in 1L treatment of NSCLC was previously shown to significantly prolong patient’s overall and progression-free survival, irrespective of PD-L1 expression levels, in the randomized, double-blind phase III ORIENT-11 trial (n=397). [Lung Cancer 2022;171:56-60] “In addition to expanding life span, another essential goal of tumour treatment is to maintain or improve HRQoL. Here, we report the patient-reported outcomes [PRO] analysis findings of ORIENT-11,” wrote the investigators.

Of all patients in the ORIENT-11 trial, 94.7 percent in the sintilimab-combination group and 93.9 percent in the placebo-combination group had a baseline and at least one postbaseline PRO assessment. PROs were measured using the European Organization for Research and Treatment of Cancer Quality of Life of Cancer Patients Questionnaire Core 30 items (EORTC QLQ-C30) and the Lung Cancer Symptom Scale (LCSS) questionnaire. PRO analysis was performed as a prespecified exploratory endpoint. [Lung Cancer 2025;doi:10.1016/j.lungcan.2025.108108]

Baseline global health status/quality of life (GHS/QoL) scores in the sintilimab-combination and placebo-combination groups were 65.7 and 63.5, respectively. The mean GHS/QoL scores were maintained in both groups from baseline to week 12. There was a modest decline in GHS/QoL scores from baseline to week 21 in both groups. Compared with the placebo-combination group, the overall improvement or stability rates for GHS/QoL were higher (60.7 vs 47.9 percent) and the overall deterioration rate was lower in the sintilimab-combination group (37.3 vs 51.2 percent). Improved GHS/QoL scores were reported by 48.4 percent of patients in the sintilimab-combination group and 34.1 percent of patients in the placebo-combination group. GHS/QoL scores remained stable in 12.3 and 13.8 percent of patients in the respective groups, while they deteriorated in 37.3 and 51.2 percent of patients, respectively.

Least square (LS) mean changes favoured the sintilimab-combination arm for most functional and symptom domains vs the placebo-combination arm from baseline to week 12 and week 21. The declines of physical, emotional, role, cognitive, and social function scores were more pronounced in the placebo-combination vs sintilimab-combination group at week 21, with a significant difference between groups in physical function. The LS mean score of role function was significantly worsened in the placebo-combination group at week 21, exceeding the minimally clinically important difference.

“Notably, the pain score worsened in the placebo-combination group at weeks 12 and 21 and gradually deteriorated further with the extension of treatment time. In contrast, this was improved in the sintilimab-combination group at weeks 12 and 21, and this improvement persisted over time with later treatment,” reported the investigators. “These findings suggest that sintilimab may be a more applicable choice for patients with cancer pain at baseline.”

The overall improvement or stability rates were 61.1 percent in the sintilimab-combination group vs 54.5 percent in the placebo-combination group for physical function, 85.3 vs 74.8 percent for pain, 78.6 vs 62.6 percent for fatigue, 88.1 vs 75.6 percent for nausea and vomiting, and 65.5 vs 50.0 percent for constipation.

The LS mean three-item global index (3-IGI) scores decline in the sintilimab-combination group was statistically significant from baseline to week 12 (difference value: -9.53 points; p=0.015) and week 21 (difference value: -9.79 points; p=0.023). The decline degree of LS mean 3-IGI scores was greater in the sintilimab-combination group than in the placebo-combination group at weeks 12 and 21, but did not reach statistical significance. The overall improvement or stability rates on average symptom burden index were 80.5 percent in the sintilimab-combination group and 85.3 percent in the placebo-combination group, respectively; the deterioration rates were 19.5 and 13.9 percent, respectively. The overall improvement or stability rates on 3-IGI were 78.0 and 82.9 percent in the sintilimab-combination and placebo-combination groups, respectively, while the deterioration rates were 17.9 and 13.1 percent, respectively. The investigators described QoL outcomes, as measured by the LCSS, as “consistent with the results of the EORTC QLQ-C30 analysis”.

“In summary, adding sintilimab to standard chemotherapy does not impair HRQoL. As such, it can maintain or improve HRQoL and various disease-related symptoms, supporting its clinical application in advanced NSCLC,” they concluded.