Search

e21578 Background: Both immunotherapy (IO) and targeted therapy (TT) are approved as adjuvant (Adj) treatment for stage III melanoma, as they have proven to significantly decrease disease recurrence. While there is evidence to suggest overall survival (OS) benefit with TT, data demonstrating OS advantage with Adj IO is lacking. There are no prospective head-to-head trials to date comparing these two treatment modalities. Our aim is to determine whether Adj IO equally improves outcomes compared to Adj TT. Methods: We retrospectively analyzed 104 patients (pts) with resected stage III melanoma who received Adj IO or TT from 1/2016 - 12/2021. Relapse free survival (RFS), distant metastasis free survival (DMFS) and OS rates were assessed between the 2 groups. Results: Of 104 pts, 78 received IO (91% nivolumab, 7% pembrolizumab, 2% other) and 26 pts TT (100% dabrafenib/trametinib). Median follow up was 21 months. At data cutoff, among the 26 pts who received TT, 50% completed 1 year of planned therapy, whereas 50% discontinued TT prematurely (42% due to adverse events [AEs], 8% due to disease relapse). Among the 78 pts who received IO, 70% completed 1 year of planned treatment or continued to receive IO at the end of the study, whereas 30% discontinued IO prematurely (18% due to disease relapse, 12% due to AEs). Relapsed disease was noted in 6/26 (23%) and 27/78 (34.6%) pts of the TT and IO groups, respectively. With regards to location of recurrence, in the TT group 2/6 pts relapsed locally and 4/6 distally, whereas in the IO group 14/27 pts relapsed locally and 13/27 distally. The estimated median RFS of the TT vs IO groups was not reached (NA) (95% Cl: 17 months, NA) vs. 30 months (95% CI: 17 months, NA) respectively, which was not statistically significant (p = 0.49). Comparison of DMFS rate was found not to be statistically significant between the 2 groups (p = 0.86). Finally, median OS was NA in either group. At the end of the study 91% and 90.5% of the pts in the TT and IO arms, respectively, were still alive. The most common AEs in the TT group were fatigue (23%), fever (23%), nausea/vomiting (19%), whereas in the IO group were fatigue (22%), hypothyroidism (14%), diarrhea/colitis (10%), pruritic rash (9%). Conclusions: Both TT and IO appear to equally decrease disease recurrence, locally or distally, when given as Adj therapy for stage III melanoma. Prospective, randomized control trials with longer follow up and larger sample size are warranted to determine any difference in potential OS benefit.[Table: see text]

e21560 Background: Prognosis in melanoma with brain metastasis is poor with a median survival of four months and a one-year survival rate of 10–20%. There is an unmet need for surveillance methods that can supplement imaging at regular intervals. Serial analysis of circulating tumor DNA (ctDNA) may aid surveillance and prognostication. A PCR-based, “specimen in/result out” testing device was employed to detect BRAF variants in plasma-derived ctDNA to evaluate the utility of rapid biomarker detection in the management of melanoma with brain metastasis. Methods: Serial blood samples from patients diagnosed with BRAF mutation-positive metastatic melanoma were collected at regular intervals. We employed a real-time PCR-based automated mutation detection system (Idylla; Biocartis, Belgium) to interrogate the plasma samples. The ctDNA mutation detection trend was analyzed relative to disease progression. Results: 39 patients with BRAF mutation positive melanoma were enrolled. 29 patients were treated in the metastatic setting, 10 in the adjuvant setting. 18 of the 29 patients with metastatic disease (62%) had brain metastases. Circulating BRAF mutation was detected in 17 of the 29 (59%) patients with metastatic disease, and was not detected in any patients treated adjuvantly. In the group with metastatic disease, this circulating biomarker changed from undetectable to detectable in eight (28%) and detectable to undetectable in three (10%). No change in circulating mutation status occurred in 18 (62%). In the eight patients who had an initial negative test that later became positive, seven (87%) had brain metastases. In three patients, ctDNA mutation detection occurred before the diagnosis of brain metastases on imaging, with a median lead time of five weeks (range, 3-12 weeks). In one patient with de novo metastatic disease admitted to the ICU, tissue was unavailable for BRAF testing but plasma was found to be positive for ctDNA BRAF detection. BRAF/MEK targeted therapy resulted in a sustained objective response. Five of six (83%) patients that had persistent ctDNA positivity had brain metastases. Among patients with brain metastases, median overall survival (mOS) of patients demonstrating >50% test positivity was numerically longer than those with