Immune-based therapies continue to show promising signals for patients with small cell lung cancer (SCLC) and mesothelioma, but better predictive biomarkers are needed to determine who is most likely to benefit, according to Justin F. Gainor, MD.
The rationale for immunotherapy in SCLC is growing because it is a very molecularly complex disease, Gainor said in a presentation during the 5th Annual Miami Lung Cancer Conference. While PD-L1 expression is infrequent in this space, SCLC tumors can be characterized by relatively high tumor mutation burden (TMB).
“We’ve seen responses with PD-1 monotherapy as well as with dual checkpoint blockade regardless of PD-L1 status,” said Gainor, assistant professor of medicine at Harvard Medical School and an assistant in medicine at Massachusetts General Hospital. “The combination of PD-1/CTLA-4 is associated with a higher response rate compared with nivolumab alone, but this benefit appears to be most pronounced in high TMB patients.”
Signals with checkpoint inhibitors were first reported with pembrolizumab (Keytruda) in the multi-cohort KEYNOTE-028 trial, which showed that the PD-1 inhibitor pembrolizumab was associated with a 33% overall response rate (ORR) in patients with PD-L1-positive SCLC. Of all patients enrolled on the study, 31.7% tested PD-L1 positive, defined as ?1% PD-L1 expression in tumor and inflammatory cells or stroma.
Nivolumab (Opdivo) has also been investigated in several SCLC studies. The open-label, phase I/II CheckMate-032 trial, for example, evaluated 216 patients with progressive SCLC who had received ?1 prior platinum-containing regimen and were not stratified for PD-L1 expression. Patients were randomly assigned to single-agent nivolumab or the combination of nivolumab and ipilimumab (Yervoy) at 1 of 2 doses.[Article continues at original source]
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