Dr. Farago on Frontline Immunotherapy Versus Maintenance Immunotherapy in SCLC

Anna F. Farago, MD, PhD, medical oncologist at the Center for Thoracic Cancers at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, discusses the use of frontline immunotherapy versus maintenance immunotherapy in patients with small cell lung cancer (SCLC).

Frontline chemotherapy combined with immunotherapy was tested in the phase III IMpower133 study and showed a benefit in overall survival (OS) and progression-free survival (PFS). However, investigators failed to report a benefit in response rates with the combination. This led to the belief that the true effect of immunotherapy came in the maintenance setting as opposed to the upfront setting.

However, the results of the phase III CheckMate-451 trial showed the opposite to be true. In the trial, patients were randomized to receive maintenance ipilimumab (Yervoy) plus nivolumab (Opdivo), nivolumab alone, or placebo following 4 cycles of first-line platinum etoposide. The primary endpoint of the trial was an OS comparison between the ipilimumab/nivolumab arm and the placebo arm. The results were negative, showing no difference in OS between the 2 arms.

Investigators did note a trend toward an improvement in survival with the nivolumab alone arm compared with placebo, especially among patients who started nivolumab within 5 weeks of completing chemotherapy, says Farago. Although these data suggest that there may be some benefit to single-agent PD-1/PD-L1 inhibitors in the maintenance setting, it is not robust enough to apply to practice. Instead, the combination of atezolizumab (Tecentriq) and standard chemotherapy is being used in the frontline setting, after which atezolizumab can be continued into the maintenance setting, concludes Farago.