Combination treatment with dabrafenib and trametinib has demonstrated activity in patients with previously treated, rare cancers harboring the BRAF V600E mutation, according to results of the ROAR study.
These results were presented in a poster at the AACR Annual Meeting 2023 and published in Nature Medicine.
The phase 2 ROAR study (ClinicalTrials.gov Identifier: NCT02034110) enrolled 206 patients with BRAF V600E-mutated cancers. Cancer types included anaplastic thyroid carcinoma (ATC), adenocarcinoma of the small intestine (ASI), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), hairy cell leukemia (HCL), high-grade glioma (HGG), low-grade glioma (LGG), and multiple myeloma (MM).
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The patients’ mean age at baseline was 57.1 years, and 56% of patients were men. Patients had previously received chemotherapy (83%), surgery (59%), radiotherapy (46%), biologic therapy (32%), immunotherapy (16%), and other therapies.
On study, patients received dabrafenib at 150 mg twice daily and trametinib at 2 mg once daily. They were treated until disease progression, unacceptable toxicity, or death. The median duration of exposure to dabrafenib was 12.5 months, and the median duration of exposure to trametinib was 12.0 months.
The primary endpoint was investigator-assessed overall response rate (ORR). The ORR was higher than 50% across all cohorts except the HGG cohort (33%) and the GIST cohort. The GIST cohort consisted of 1 patient, and this patient’s best response was stable disease.
Data on ORR, duration of response (DOR), progression-free survival (PFS), and overall survival (OS) across the cohorts can be seen in the table below.
|
Investigator-Assessed Outcomes by Cancer Type |
||||
|
Cancer Type |
ORR |
Median DOR |
Median PFS |
Median OS |
|
ATC (n=36) |
56% |
14.4 months |
6.7 months |
14.5 months |
|
ASI (n=3) |
67% |
7.7 months |
9.5 months |
21.8 months |
|
BTC (n=43) |
53% |
8.9 months |
9.0 months |
13.5 months |
|
HCL (n=55) |
89% |
Not reached |
Not estimable due to few events |
Not estimable due to few events |
|
HGG (n=45) |
33% |
31.2 months |
5.5 months |
17.6 months |
|
LGG (n=13) |
54% |
Not reached |
Not estimable due to few events |
Not estimable due to few events |
|
MM (n=10) |
50% |
11.1 months |
6.3 months |
33.9 months |
Across all cohorts, treatment-related adverse events (TRAEs) occurred in 87.9% of patients. The most common TRAEs were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%), and rash (20.4%).
A total of 111 patients (54%) died. Twenty deaths (9.7%) occurred within 30 days from the last dose of study treatment. Most deaths (n=90) were due to disease progression, and there were no treatment-related deaths.
These results were used to support the US approval of dabrafenib and trametinib for patients with advanced solid tumors harboring BRAF V600E mutations.
Disclosures: This research was supported by Novartis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.
References
1. Subbiah V, Kreitman RJ, Wainberg ZA, et al. Tumor-agnostic efficacy and safety of dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: ROAR basket study. AACR 2023. April 14-19, 2023. Abstract CT083.
2. Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: The phase 2 ROAR trial. Nat Med. Published online April 14, 2023. doi:10.1038/s41591-023-02321-8
