Cytisinicline for smoking cessation among patients with a history of cancer: A post-hoc analysis from two phase 3 clinical trials.

Abstract

e22676 Background: Smoking cessation may reduce recurrent and secondary cancers, and extend survival. Cytisinicline, a plant-based alkaloid that acts as a partial agonist of α4β2 nicotinic acetylcholine receptors, significantly increased smoking cessation vs placebo in two phase 3 trials (ORCA-2 [NCT04576949]; ORCA-3 [NCT05206370]). We present a post-hoc analysis evaluating the outcomes from participants who reported a history of cancer at baseline. Methods: The two RCTs enrolled a similar population of adults who currently smoked ≥10 cigarettes per day and who had at least 10ppm exhaled carbon monoxide values at baseline. Volunteers were randomly assigned to behavioral support with either cytisinicline 3 mg three times daily for 6 or 12 weeks, or placebo. This post-hoc analysis evaluated outcomes in 120 of the 1602 participants who reported a baseline cancer history (placebo, n = 38; cytisinicline 6 wks, n = 45; cytisinicline 12 wks, n = 37). The primary efficacy outcome was biochemically confirmed continuous smoking abstinence during the last 4 wks of treatment. Treatment-emergent adverse events (TEAEs) and associated treatment discontinuation were evaluated. Results: Among those included in this analysis, 77 patients (64.2%) were female; 108 patients (90.0%) were white; mean age 60.6 (SD 9.4) years; mean duration of smoking 44.4 (SD 10.9) years. Most common malignancies were basal cell carcinoma (n = 31), breast cancer (n = 21), and squamous cell carcinoma (e.g. lung, skin; n = 19). Cytisinicline increased continuous abstinence for the 6-wk treatment group for 11/45 (24.4%) vs 4/38 (10.5%) placebo at wks 3–6 (odds ratio [OR] 2.75 [95% CI 0.81–10.74]); and in the 12-wk cytisinicline treatment group for 12/37 (32.4%) vs 6/38 (15.8%) placebo at wks 9–12 (OR 2.56 [95% CI 0.84–8.24]). In the entire pooled cohort, cytisinicline was well tolerated (most common TEAEs observed in ≥5% of patients and with a frequency ≥2% higher in the cytisinicline vs placebo group were insomnia and abnormal dreams), with no serious treatment-related TEAEs, and treatment discontinuation due to adverse events of < 3% across treatment groups. Conclusions: Cytisinicline was well tolerated and showed numerically higher smoking cessation rates compared with placebo in a small cohort of patients with a history of malignancy. Smoking cessation remains an underutilized but highly modifiable determinant of cancer outcomes, including treatment efficacy, recurrence, and survival. While exploratory in nature, these findings suggest that cytisinicline offers a promising pharmacologic option to support smoking cessation in cancer survivors. Clinical trial information: NCT04576949 ; NCT05206370 .