KEY TAKEAWAYS
- A Phase III DREAMseq clinical trial estimated the efficacity of the original treatment or treatment sequence for cases with preliminarily undressed BRAF V600- mutant metastatic carcinoma.
- Cases were aimlessly assigned to admit either a combination of nivolumab/ ipilimumab (arm A) or dabrafenib/ trametinib (arm B) in the first stage of the study and also switched to the alternate remedy upon complaint progression.
- The primary outgrowth measured was two-time overall survival.
- The results of the trial demonstrated that the two-time overall survival rate for those starting with a combination of nivolumab/ ipilimumab was 71.8 (95% CI, 62.5 to 79.1), compared to 51.5 (95% CI, 41.7 to 60.4) for those starting with dabrafenib/ trametinib (log-rank P = .010).
- The objective response rates for arms A, B, C, and D independently were 46.0, 43.0, 47.8, and 29.6.
- The findings of this trial suggest that a combination of nivolumab/ ipilimumab followed by BRAF and MEK asset remedy, if necessary, is the optimal treatment sequence for utmost cases with BRAFV600- mutant metastatic carcinoma.
In a randomized, phase III clinical trial, cases with treatment-naive BRAFV600– mutant metastatic carcinoma were given the choice of either nivolumab/ ipilimumab combination remedy (arm A) or dabrafenib/ trametinib (arm B) as their initial treatment. Upon complaint progression, they also enrolled in step 2 and were allowed to admit an alternate remedy, dabrafenib/ trametinib (arm C) or nivolumab/ ipilimumab (arm D). The primary endpoint was two-time overall survival(zilch), and the secondary endpoints included three-time OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety.
The trial included 265 cases, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped beforehand due to the Data Safety Monitoring Committee’s recognition of a clinically significant endpoint. The results showed that the combination of nivolumab/ ipilimumab as the initial treatment had the loftiest two-time OS rate at 71.8 (95% CI, 62.5 to 79.1), compared to 51.5 (95% CI, 41.7 to 60.4) for those in arm B (log-rank P = .010). Also, those in arm A had more remarkable progression-free survival (P = .054). The objective response rate was loftiest in arms A and C at 46.0 and 47.8, compared to 43.0 and 29.6 in arms B and D, independently. The median duration of response wasn’t reached for arm A and 12.7 months for arm B (P<.001).
Crossover passed in 52 of the cases with proven complaint progression. Grade ≥ 3 venom passed with an analogous frequency between arms, and the authority toxin biographies followed prospects. The results of this trial suggest a combination of nivolumab/ ipilimumab followed by BRAF and MEK asset remedy, if necessary, is the most effective treatment sequence for utmost cases with BRAFV600- mutant metastatic carcinoma, leading to broad nonsupervisory blessing.
Source:https://pubmed.ncbi.nlm.nih.gov/36166727/
Clinical trial:https://clinicaltrials.gov/ct2/show/NCT02224781
Atkins, M.B., Lee, S.J., Chmielowski, B., Tarhini, A.A., Cohen, G.I., Truong, T.-G., Moon, H.H., Davar, D., O’Rourke, M., Stephenson, J.J., Curti, B.D., Urba, W.J., Brell, J.M., Funchain, P., Kendra, K.L., Ikeguchi, A.P., Jaslowski, A., Bane, C.L., Taylor, M.A. and Bajaj, M., Conry R, Ellis R, Logan T, Laudi N, Sosman J, Crockett D, Pecora A, Okazaki I, Reganti S, Chandra S, Guild S, Chen H, Streicher H, Wolchok J, Ribas A, and Kirkwood J (2022). Combination dabrafenib and trametinib versus combination nivolumab and ipilimumab for patients with advanced BRAF-mutant melanoma: The DREAMseq Trial – ECOG-ACRIN EA6134. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, [online] p.101200JCO2201763. doi:https://doi.org/10.1200/JCO.22.01763.
