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Settled the order question: for BRAF-mutant melanoma, start with immunotherapy and save the targeted pills for later.
DREAMseq, ECOG-ACRIN trial EA6134, NCT02224781, sponsored by ECOG-ACRIN and the NCI and reported in 2021, settled the order question in BRAF-mutant metastatic melanoma: start with immunotherapy and save the targeted tablets for later. It randomised 265 patients to nivolumab plus ipilimumab followed by dabrafenib plus trametinib at progression, or the reverse sequence, and was stopped early for benefit when two-year overall survival clearly favoured immunotherapy first, since targeted therapy remained effective after immunotherapy while immunotherapy after BRAF and MEK failure performed poorly. OnCo links it to BRAF, PD-1 and CTLA-4 as targets, the drugs, ECOG-ACRIN and the pairing that places immunotherapy first, and the Italian phase 2 SECOMBIT reached the same conclusion. Whether a short targeted induction before immunotherapy could improve on either sequence is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
267 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival at 2 yearsprimary | Immunotherapy first | - | 71.8% | - | 0.010 | link |
| Targeted therapy first | - | 51.5% |
Shares CTLA-4, Advanced melanoma (unresectable stage III and stage IV), Ipilimumab, Nivolumab.
Shares DREAMseq (ECOG-ACRIN EA6134): sequencing dabrafenib-trametinib and nivolumab-ipilimumab in BRAF-mutant metastatic melanoma, BRAF V600-mutant melanoma, Advanced melanoma (unresectable stage III and stage IV), Melanoma.
Shares Advanced melanoma (unresectable stage III and stage IV), BRAF, Ipilimumab, Nivolumab.
Shares BRAF V600-mutant melanoma, CTLA-4, BRAF, Ipilimumab.
Shares CTLA-4, Advanced melanoma (unresectable stage III and stage IV), Ipilimumab, Nivolumab.
Shares CTLA-4, Advanced melanoma (unresectable stage III and stage IV), Ipilimumab, PD-1.
Shares CTLA-4, Advanced melanoma (unresectable stage III and stage IV), Ipilimumab, Nivolumab.
Shares BRAF V600-mutant melanoma, BRAF, Ipilimumab, Nivolumab.