Pharmacotherapy as an adjunct to behavioral weight loss treatment in survivors of breast cancer.

11039 Background: Approximately half of breast cancer (BC) survivors attain 5% weight loss with 6 months of behavioral intervention alone. We conducted a single-arm, phase II study evaluating the addition of FDA-approved anti-obesity pharmacotherapy Contrave (Naltrexone +Buproprion) to a behavioral weight loss (BWL) intervention in BC survivors who did not attain 5% weight loss after 8 weeks. Methods: Women with stage 0-III BC and BMI > 27 kg/m 2 who completed local therapy and chemotherapy were enrolled in a 6-month, remotely-delivered BWL program. Patients completed demographic and psychosocial surveys, lab draws (Hba1c and lipid panel) and were weighed in clinic at baseline, 2 and 6 months. An adaptive design utilizing weight loss at 2 months identified those with greater likelihood of weight loss at 6 months with BWL alone. Patients with and without ≥5% weight loss at 2 months were stratified as FAST-BWL and SLOW-BWL, respectively. FAST-BWL continued BWL alone for 4 months, while SLOW-BWL received Contrave plus BWL. Within the SLOW-BWL arm, the trial continued with a Simon two-stage minimax design with the proportion of SLOW-BWL attaining ≥5% weight loss at 6-months as the primary endpoint. The planned sample size of 30 had 80% power at a type I error rate of 5% if the true rate of attaining the primary endpoint by 6 months was 29%, compared to 10.9% under the null. Secondary endpoints included measures of physical function, endocrine function, pain, fatigue, depression, anxiety, sleep disturbance, and sexual problems. Results: Of 53 enrolled patients, 15 (28%) were FAST-BWL and 38 (72%) were SLOW-BWL responders. Compared to FAST-BWL, SLOW-BWL included more participants who were Black (32% v 7%), premenopausal (21% v 7%), and had an ECOG 1 (26% v 13%). At 6-months, mean % weight change was -5.1±2.9 and -10.8±3.5 for SLOW-BWL and FAST-BWL, respectively. In the intent-to-treat population of SLOW-BWL (n = 38), 42% had 5% weight loss by 6-months. SLOW-BWL had significant improvement in Hba1c between 2 and 6 months. Among SLOW-BWL patients, every two pounds over the two-month average change, patients were one third as likely to be successful at 6 months, OR = 0.3 (95% CI: 0.1, 0.88), p = 0.03. Of 21 in SLOW-BWL with PROs evaluable for minimally important differences at 6-months, 29% had less anxiety, 24% had improved physical function, and 19% had less pain, fatigue, sleep disturbance, and sexual dysfunction. Regardless of arm, physical function and pain improved in those with >5% weight loss (p = 0.03 and p = 0.02, respectively). The change in pain was primarily in those with > 5% weight loss in SLOW-BWL. Conclusions: Contrave can enhance weight loss outcomes in BC survivors who do not attain significant weight loss with diet and exercise modification alone. Further research is needed to understand individuals who benefit most from pharmacotherapy. Clinical trial information: NCT04499950 .