Dr. Chiang on the Rationale for Chemoimmunotherapy in Lung Cancer

Anne Chiang, MD, PhD, an associate professor at the Yale School of Medicine, as well as the chief network officer and deputy chief medical officer with Smilow Cancer Network, discusses the rationale for combining immunotherapy with chemotherapy in lung cancer.

The rationale for using a combination of immunotherapy and chemotherapy in lung cancer is important to consider, says Chiang. The cytotoxic effects of the chemotherapy can be used to reduce tumor burden, but a whole host of effects can also make an environment more conducive to the effects of immunotherapy, explains Chiang. For example, the T-cell-to-tumor-cell ratio can be improved, T-cell inhibitory substances can be reduced, and tumor barriers can be altered, such as the pressure or the vasculature, to allow for better T-cell penetration.

The signaling may attract more T cells and their ultimate effects, which can enable tumor cells to be killed in a way that allows downstream signaling; this prompts dendritic cell activation, migration, and, ultimately, presentation of antigens in the lymph nodes and tumor microenvironments. That is the rationale behind why a combination of chemotherapy and immunotherapy would be particularly effective in patients with lung cancer. For example, in the CheckMate-9LA trial, patients with non–small cell lung cancer were treated with nivolumab (Opdivo) plus ipilimumab (Yervoy) in combination with chemotherapy. The rationale for adding 2 cycles of chemotherapy is to harness the immediate cytotoxic effect, as previous trials with immune checkpoint inhibitors show that it takes time for the therapy to work, concludes Chiang.