TAFINLAR is indicated, in combination with trametinib, for...the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.

...- Known positive RAS (NRAS or KRAS or HRAS) or BRAFV600E or K601E mutation (determined on a previous analysis and/or on a representative formalin-fixed paraffin embedded (FFPE) tumor samples sent for central testing or on a biopsy sample sent for central testing)....

The ORR was 72.0% (18 of PR) and disease control rate was 88.0%. The progression-free survival (PFS) rate at 6 months was 83.6%...Dabrafenib plus trametinib showed high ORR with symptom improvement, however, majority of patients needed dose reduction in patients with BRAF V600E-mutated metastatic PTC.

Patients were treated with dabrafenib (150 mg bid) and trametinib (2 mg per day) for 42 days….Among the 24 patients (mean age 67 years, 15 females) with a BRAFV600E mutated RAI refractory papillary DTC included between March 2018 and January 2020…The RECIST 6-months tumor response (central review) was partial response (PR) in 38% (95%CI 18-61), stable disease (SD) in 52% (95% CI 30-74) and progressive disease (PD) in 10% (95% CI 1-30).

Two consecutive patients with symptomatic, metastatic radioactive iodine-resistant BRAFV600E mutated papillary thyroid cancer and poor performance status were treated initially with dabrafenib 150 mg twice daily plus trametinib 2 mg once daily…They continue to show evidence of antitumor activity 27 and 18 months respectively from the start of treatment and 15 and 13 months respectively from the start of the first break using intermittent dosing.

We present the case of a locally aggressive unresectable differentiated BRAFv600E mutated papillary thyroid cancer that responded to neoadjuvant dabrafenib and trametinib regimen over the course of 3 months…

A 59-year-old caucasian female with radioactive iodine-refractory metastatic thyroid papillary carcinoma with BRAFV600E mutation was treated with dabrafenib and trametinib as a compassionate use….A follow-up PET–CT scan was performed in January 2019. Tumor was on radiological partial response. In addition, there was intestinal pneumatosis with mild sign of pneumoperitoneum (Fig. 3).

A 67-year-old woman diagnosed with PTC underwent total thyroidectomy with central neck dissection…. Her tissue from previously resected metastatic lymph nodes was assessed by PCR for the presence of a BRAF mutation and found to be positive for BRAF V600E. She was then enrolled in another clinical trial () and randomly assigned to combination therapy with dabrafenib, 150 mg twice daily, and trametinib, 2 mg daily. After 2 cycles, she sustained a partial response (PR) in the thyroid bed, cervical and intrathoracic lymph nodes, and pulmonary lesions...

CONTRADICTING EVIDENCE: In the 8305c ATC xenograft model (BRAF V600E mutation), treatment with the standard of care combination of dabrafenib (BRAF inhibitor) + trametinib (MEK inhibitor) was cytostatic with tumors resuming rapid growth within 20 days. In those mice that developed resistance to standard of care, the triple therapy of SGK1i + dabrafenib + trametinib was effective at overcoming the resistance and restored activity of dabrafenib and trametinib leading to substantial tumor regression.

In the 8305c ATC xenograft model (BRAF V600E mutation), treatment with the standard of care combination of dabrafenib (BRAF inhibitor) + trametinib (MEK inhibitor) was cytostatic with tumors resuming rapid growth within 20 days. In those mice that developed resistance to standard of care, the triple therapy of SGK1i + dabrafenib + trametinib was effective at overcoming the resistance and restored activity of dabrafenib and trametinib leading to substantial tumor regression. In a comparator arm, initial treatment with the triple therapy of SGK1i + dabrafenib + trametinib resulted in 80‐90% sustained tumor regression in all 8 mice treated for >25 days.