Objectives:

Evidence shows that programmed death receptor-1 (PD-1)-blocking and human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibodies display apparent benefits in lung cancer therapy. Further, lung cancer patients who receive nivolumab (PD-1 inhibitor) plus ipilimumab (CLTA-4 inhibitor) in combination have higher overall survival rate than those treated with ipilimumab alone. However, adverse events (AE) are still a concern, especially gastrointestinal (GI) AEs. Since GI AE is one of the most common reasons for patients stopping immunotherapy, we utilized real-world data to gain insight in the incidence and severity of GI AEs among lung cancer patients treated with nivolumab and ipilimumab.

Methods:

A retrospective study was conducted using electronic health records (EHR) data from the OneFlorida clinical research network. We identified lung cancer patients who were prescribed with ipilimumab alone, nivolumab alone, or combination of ipilimumab and nivolumab as study cohorts. GI AEs in observation windows were extracted for these patients. We then built a multivariate cox proportional hazard model to estimate the hazards of GI AEs by treatment, adjusting for ages, genders, race ethnicities, and duration of treatment.

Results:

The study cohort had 1519 patients (1313 nivolumab, 6 ipilimumab, and 200 combination). Patients treated with ipilimumab alone were removed because of small sample size. Overall, 553 (36.4%) of the patients had at least one GI AE. Among those GI AEs, 131 (23.7%) of them had led to hospitalizations. The median GI AE free time was 272 days (95% CI: 242 – 343 days). The hazard ratio of having GI AE for patients with combination treatment verse with nivolumab alone was 1.36 (95% CI: 1.08 – 1.71).

Conclusions:

GI AEs are common in lung cancer patients treated with nivolumab and ipilimumab. Patients treated by combination treatment have significantly higher hazards than those treated by nivolumab alone.