Tafinlar Plus Mekinist Triples Progression-Free Survival in Thyroid Cancer

Patients with locally advanced or metastatic differentiated thyroid cancer whose disease no longer responds to radioactive iodine and carries a BRAF V600E mutation participated in a global phase 3 trial.

Results showed those treated with Tafinlar (dabrafenib) plus Mekinist (trametinib) lived longer without their disease worsening than those given placebo.

Tafinlar blocks the activity of the mutated BRAF protein, and Mekinist blocks a related protein called MEK. Together, the drugs target the signaling pathway that allows cancer cells with the BRAF V600E mutation to grow.

Prior to this trial, Tafinlar and Mekinist were approved together for an alternative, more aggressive form of BRAF V600E-positive thyroid cancer.

All participants in this trial had tried one or two VEGFR-targeted therapies, an earlier type of targeted treatment, that had stopped working.

In a global phase 3 trial reported in The Lancet Oncology, "These findings support the second-line use of dabrafenib [Tafinlar] plus trametinib [Mekinist] in patients with radioactive iodine-refractory BRAF V600E-positive differentiated thyroid cancer."

What did the study find?

Tafinlar plus Mekinist extended progression-free survival to a median of 12.8 months, compared with 3.7 months on placebo.

Patients who received Tafinlar plus Mekinist had a 62% lower risk of their cancer progressing or dying compared with those who received placebo.

The combination also helped shrink tumors in 57% of patients, compared with 4% of those who received placebo. About 6% of patients in the combination group had no detectable signs of their tumors after treatment, compared with 2% in the placebo group.

Overall, 88% of patients receiving Tafinlar plus Mekinist either saw their tumors shrink or had their cancer remain stable. This was compared with 63% of patients who received placebo.

Researchers also looked at overall survival, but there was not yet enough information to determine whether the combination helped patients live longer. The median overall survival had not yet been reached in the Tafinlar-plus-Mekinist group, meaning more than half of those patients were still alive when the analysis was conducted. In the placebo group, median overall survival was 25.9 months.

Relatively few patients had died at the time of the analysis according to researchers. Nearly all eligible patients in the placebo group later switched to Tafinlar plus Mekinist after their cancer progressed, which made it harder to determine whether the combination improved overall survival.

How was the trial designed?

Researchers enrolled 153 adults with locally advanced or metastatic, radioactive iodine-refractory, BRAF V600E-positive differentiated thyroid cancer at 42 sites in 11 countries between December 2021 and May 2024. All participants had papillary thyroid cancer confirmed by biopsy and were able to carry out most or all daily activities independently.

Patients were randomly assigned in a 2-to-1 ratio to receive Tafinlar (150 mg twice daily) plus Mekinist (2 mg once daily) or matching placebo pills. Neither patients nor their doctors knew which treatment was being given.

The trial's main goal was to measure how long patients lived without their cancer growing or spreading, known as progression-free survival. Scans were reviewed by an independent group not involved in running the trial.

Researchers also tracked how long patients lived overall, how many patients' tumors shrank, how long that shrinkage lasted, and the side effects.

What side effects did patients experience?

Side effects of any severity occurred in 98% of patients receiving Tafinlar plus Mekinist, compared with 90% of those receiving placebo. The most common side effects with the combination were fever (48%) and anemia (45%).

Serious side effects occurred in 43% and 25% of patients, respectively. Pneumonia was the most common serious side effect, occurring in 8% and 2% of patients, respectively.

Side effects led to treatment discontinuation in 8% and 6% of patients, respectively.

One patient receiving Tafinlar plus Mekinist died from a treatment-related stroke. Other fatal side effects in that group included pneumonia, irregular heartbeat, a second stroke, severe blood infection and a new skin cancer, each occurring in one or two patients. Two patients in the placebo group died from causes investigators did not consider related to treatment.

A condition called serous retinopathy, a buildup of fluid under the retina that can affect vision, occurred in 7% of patients who received Tafinlar plus Mekinist and none of the patients who received placebo.

Researchers said the overall side effect pattern was consistent with previous studies of Tafinlar plus Mekinist, with no new safety concerns identified.

References

1. Gao M, Park YJ, Lin C-C, et al. "Efficacy and safety of dabrafenib plus trametinib in adults with differentiated thyroid cancer: a randomised, double-blind, placebo-controlled, phase 3 trial." The Lancet Oncology. Published July 14, 2026.
2. Barbor M. "Dabrafenib Plus Trametinib Improves Progression-Free Survival in BRAF V600E–Positive Differentiated Thyroid Cancer." The ASCO Post. Published July 27, 2026.

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