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Dr. Zeynep Eroglu, a medical oncologist in the Department of Cutaneous Oncology, presented recent research findings at the 2022 ASCO conference evaluating the association between baseline metastatic patterns and clinical outcomes among patients with BRAF-positive metastatic melanoma.

Although immunotherapy (IO) and BRAF-target therapy (TT) have shown beneficial results in BRAFV600 mutant (BRAF+) metastatic melanoma (MM), there is a lack of real-world data on the impact of systemic therapy outcomes based on characteristics such as site and number of baseline metastases. Patients with >1 baseline site and certain sites of metastases are underrepresented or excluded in clinical trials. The objective of this study was to evaluate the association between these characteristics and survival among BRAF+ MM patients.

A retrospective cohort study was exercised using the Novartis BRAF+ melanoma patients ObsErvational (NOBLE) dataset – harmonized customized data from Flatiron and ConcertAI. It included patients ≥18 years, who received treatment with a first-line (1L) IO (anti-PD-1 mono or combination therapy ipilimumab + nivolumab) or TT (any BRAF/MEK-inhibitors) after 1/1/2014. Progression-free survival (PFS) and overall survival (OS) for IO and TT were analyzed according to number (1, 2, 3+ sites) and location (brain, lung, liver, bone) of baseline metastasis. Treatment sequence from 1L to 2L (i.e. IO/TT vs TT/IO) were also compared for PFS and OS outcomes.

In total, 1,961 patients were observed, 620 patients (32%) on IO monotherapy, 501 patients (26%) on IO combo therapy, and 840 patients (43%) on TT in the 1L. When  for sex, age, ECOG, and Charlson Comorbidity Index, there was no difference in PFS or OS between 1L IO mono, IO combo and TT therapies in patients who had 1, 2, or 3+ baseline metastases. Factors such as sex, age, ECOG, and Charlson Comorbidity Index were considered, but presented no difference in PFS or OS between 1L IO mono, IO combo and TT therapies in patients who had 1, 2, or 3+ baseline metastases. Additionally, patients who had either baseline brain, liver, lung, or bone metastasis, presented no difference in PFS and OS between IO mono, IO combo, and TT combo therapies. Of the 521 patients included in the sequencing analysis (only patients who received 2L therapy), 239 patients (46%) had 1L IO/2L TT. There was no difference in PFS or OS between treatment sequences for patients with any number or location of baseline metastasis.

Outcomes stratified by number of metastases and metastatic site among patients who received sequencing therapy 1L TT/2L IO. 

Reference group: 1L IO/2L TT PFS OS
Number of metastases N HR 95% CI HR 95% CI
1 165 0.96 0.57 - 1.61 1.51 0.53 – 4.34
2 132 0.56 0.29 - 1.07 0.95 0.22 – 4.03
3+ 218 0.75 0.54 – 1.04 1.43 0.60 – 3.38
Metastatic site          
Brain 177 0.82 0.49 – 1.38 1.45 0.41 – 5.14
Liver 150 1.00 0.59 – 1.70 0.57 0.22 – 1.53
Lung 272 0.89 0.61 – 1.29 1.22 0.58 – 2.53
Bone 160 1.24 0.76 – 2.02 1.57 0.59 – 4.17

HR = Hazard ratio; CI = confidence interval

The results of this study determined no difference in survival between 1L TT and IO for BRAF+ MM patients. The outcomes presented that these methods are comparable regardless of number and location of metastases, including brain metastasis. Whether switching from 1L TT to IO before progression may account for differences compared to trial data, further investigation will be explored.

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