Targeted Therapies and the Sequencing of Immuno-Oncology Drugs

Immunotherapies work by enhancing what the immune system already does. Although the body recognizes a tumor as foreign, tumors find a work-around by hijacking systems that suppress the immune response, states Andrew L. Pecora, MD. Researchers understand far more about this complex dynamic than just a few years ago. The drugs available today can make the tumor more recognizable to the immune system.

Treatment decisions begin with mutation analyses. In melanoma, patients with a BRAF mutation will usually be treated with a BRAF inhibitor plus a MEK inhibitor. This is not curative, but will control the disease for about 1 year, says Pecora. Oncologists may start considering an immuno-oncology drug at this point, although the exact sequencing and timing is a matter of debate. Some oncologists will give the immuno-oncology drug first if the disease is slow-growing.

Ipilimumab is approved as a first-line agent in metastatic melanoma. Data showing that pembrolizumab is superior to ipilimumab may lead to the approval of pembrolizumab in this setting, notes Pecora. Data have also shown that combining an anti-CTLA4 agent with an anti-PD-1 drug is better than either drug alone; however, says Pecora, there are more immunologic-related toxicities with the combination.

Some studies suggest that high expressers of PD-1 may do well with the PD-1 inhibitor only, whereas low expressers may need the anti-CTLA4 drug as well. The field is evolving rapidly, adds Pecora, and the discussions will change just as quickly as more is learned.