This review discusses the role of the BRAF/mitogen activated protein kinase pathway in modulating antitumor immunity and how this provides a rationale for combining BRAF- targeted therapy with immunotherapy to enhance therapeutic responses. Reddy SM, Reuben A, & Wargo JA. Curr Oncol Rep 2016; 18: 42. doi:10.1007/s11912-016-0531-z

High tumor mutational burden is associated with a better response to immune checkpoint inhibitors in people with non-small-cell lung cancer across all levels of PD-L1 expression, US researchers report.

Antibiotic use is associated with poor survival outcomes in people receiving tyrosine kinase inhibitors for advanced non-small-cell lung cancer or melanoma, findings indicate.

Adjuvant therapy with BRAF/MEK inhibitors should be preferred for patients with BRAF-mutant non-ulcerated stage III melanoma.

Single-agent vemurafenib has demonstrated promising antitumor activity against non-small-cell lung cancer harboring BRAF V600E mutations in the VE-BASKET trial.

Melanoma patients with brain metastases can expect to live longer following the incorporation of checkpoint inhibitors and BRAF -targeted therapies into standard care than their counterparts treated prior to the approval of these agents, suggests an analysis of the US National Cancer Database.

In the absence of other satisfactory treatment options, the panel “strongly” recommends that clinicians should give PD-1 inhibitor therapy, such as pembrolizumab, to patients who test positive for MSI/dMMR, and the TRK inhibitors larotrectinib or entrectinib to those with NTRK fusions.

On the back of success in melanoma with PD-1 and CTLA-4 checkpoint inhibitors, attention has turned to other checkpoint proteins such as indoleamine 2,3-dioxygenase (IDO). In this editorial, Zeynep Eroglu (Moffitt Cancer Center, USA) discusses the advances and setbacks in the development of IDO inhibitors for melanoma.

The overall survival of patients with stage IV melanoma has improved on a national scale since the approval of the first-in-class immune checkpoint and BRAF inhibitors, according to a US National Cancer Database analysis.

An updated analysis of the phase III COLUMBUS trial adds to the evidence supporting a combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib in patients with advanced BRAF V600-mutant melanoma.

In addition to these, alterations were seen in a diverse range of genes such as HER2 , BRAF , KRAS , and PIK3CA , at rates of 1–7%.

Noting that BRAF mutation status has recently been reported “to describe populations with differing OS after immune checkpoint inhibitors,” the researchers conclude that their findings suggest the hypothesis that combining bevacizumab with immunotherapy “may benefit high-risk BRAF mutant melanoma patients.”

An updated analysis of the phase III COLUMBUS trial adds to the evidence supporting a combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib in patients with advanced BRAF V600-mutant melanoma.

The combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib has favorable efficacy and tolerability relative to either encorafenib or vemurafenib alone in patients with advanced melanoma harboring BRAF mutations, phase III trial findings indicate. Read the accompanying comment by Eva Muñoz Couselo

The remaining patients developed “unexpected” resistance mechanisms, with individual reports of RET , FGFR3 , and BRAF fusions and a KRAS Q61K mutation.

Tier I includes targets that are ready for implementation in routine clinical decisions, such as the anti-HER2 antibodies, including trastuzumab, for HER2 -amplified breast cancer and EGFR inhibitors for non-small-cell lung cancer patients harboring an EGFR activating mutation.

The corresponding risk reductions were a significant 42% for patients with stage IIIB and IIIC disease, 39% for patients with wild type BRAF , and 41% for those with V600E or V600K BRAF mutations.

All patients were aged 18 years and older and had histologically or cytologically confirmed surgically resectable clinical stage III or oligometastatic stage IV BRAF V600E or BRAF V600K-mutated melanoma.

Dabrafenib in combination with trametinib provides long-lasting antitumor activity in patients with previously untreated BRAF V600E-mutant metastatic non-small-cell lung cancer, with a tolerable safety profile, researchers report.