Dr Kalemkerian on Unmet Needs With the Use of Chemoimmunotherapy in ES-SCLC

Gregory Peter Kalemkerian, MD, clinical professor, medical oncology, internal medicine, the University of Michigan Health, Rogel Cancer Center, discusses the unmet needs associated with the investigation of combination chemoimmunotherapy in the frontline treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

The phase 3 IMpower133 trial evaluated the efficacy and safety of chemotherapy with carboplatin and etoposide plus either the PD-L1 inhibitor atezolizumab or placebo in patients with previously untreated ES-SCLC. At a median follow-up of 13.9 months, the median overall survival (OS) was 12.3 months with atezolizumab vs 10.3 months with placebo (HR, 0.70; 95% CI, 0.54-0.91; P = .007).

Although the use of combination chemoimmunotherapy in the frontline treatment of patients with ES-SCLC has led to OS improvements vs chemotherapy alone in a subset of patients, this approach was investigated in an all-comers patient population because of the lack of good biomarkers that are available to determine which specific patients may or may not respond to this combination approach, Kalemkerian begins. Notably, the absence of effective biomarkers exists beyond the SCLC treatment paradigm and is an issue in nearly every malignancy across the cancer care treatment arena, he notes. This lack of specific biomarkers drives the notion that investigating treatment approaches in broader patient populations is the appropriate way to approach both research and treatment with chemoimmunotherapy, since responsive and unresponsive disease subsets remain unknown, Kalemkerian emphasizes.

Longer-term research with combination chemoimmunotherapy in patients with ES-SCLC has demonstrated positive survival outcomes in certain patient subsets, Kalemkerian expands. However, trying to identify the patients most likely to respond to chemoimmunotherapy combinations before initiating this treatment remains a challenge, he notes.

Notably, preliminary research aims to determine subsets of patients with SCLC based on gene expression profiles. These evaluations are mainly investigating the expression of transcriptional factors to identify a small group of patients with SCLC who have an immune-type disease phenotype, Kalemkerian continues. It appears that these may be the patients who are responding to immunotherapy. However, research with a larger validation group is needed to know for certain whether immune phenotype is an appropriate biomarker to select for patients most likely to respond to chemoimmunotherapy, Kalemkerian concludes.