Melissa L. Johnson, MD, associate director for lung cancer research at Sarah Cannon Research Institute and partner in Tennessee Oncology, discusses the potential of tiragolumab/atezolizumab for metastatic non–small cell lung cancer (NSCLC).
Prior to this year’s virtual American Society of Clinical Oncology conference held in May, Melissa L. Johnson, MD, associate director for lung cancer research at Sarah Cannon Research Institute and partner in Tennessee Oncology, spoke with The American Journal of Managed Care® on the results of the CITYSCAPE trial, which she presented at the conference. The phase 2 results show that tiragolumab plus atezolizumab may be a chemotherapy-free treatment option for patients with metastatic non-small cell lung cancer.
How does the potential addition of a tiragolumab/atezolizumab combination to the lung cancer armamentarium change treatment decisions for oncologists?
Tiragolumab [tira] and atezolizumab [atezo] is a new immune combination that may be useful for patients and doctors who are looking for a chemotherapy-free option. It appears that tiragolumab and atezolizumab are most effective in patients whose tumors express high levels of PD-L1. There's work ongoing looking at TIGIT as a second biomarker, but right now we know that it appears to be expressed on many of the same cells as PD-L1. And so it may be that we can select for patients that have high levels of PD-L1 and that they could be treated with tiragolumab and atezolizumab in lieu of chemo and immune therapy.
How does the adverse event profile for this combination compare with other options for lung cancer?
The adverse event profile of patients treated with tiragolumab and atezolizumab was very similar to the adverse event profile of patients treated with placebo and atezolizumab. There was a little bit of an increase in the report of immune-mediated adverse events in patients treated with the combination, which is to be expected because they were getting 2 active agents. However, the rates of serious adverse events—grade 3 to 5 adverse events—and events requiring discontinuation of study therapy were similar, almost identical, between the experimental and the placebo group. I will say that as an investigator on the trial, sometimes we didn't know whether patients were getting tiragolumab or not. Sometimes it was hard to attribute the adverse event that we were reporting to atezolizumab or atezolizumab and tira, because they seem so similar.
Based on the findings from CITYSCAPE, which patients with lung cancer will be the best candidates for the tiragolumab/atezolizumab combination or this combination plus chemotherapy?
CITYSCAPE is just the beginning of our understanding of tiragolumab and atezolizumab. It will be studied subsequently in a randomized phase 3 trial, tiragolumab and atezo versus placebo and atezo in patients with PD-L1–high tumors expressing more than 50% by the Dayco 22C3 assay. And so that will strengthen the information that we've obtained in this study. I still think the best place for this immune combination is going to be for patients who are not interested in chemotherapy because quality of life is paramount. It's going to be for patients whose comorbidities perhaps preclude the addition of chemotherapy. It's going to be for patients whose PD-L1 levels are high, especially if the progression-free survival and longer end points trend in the direction that this randomized phase 2 data has done.
What comorbidities might prevent a patient from receiving chemotherapy?
Right now we are worried about giving chemotherapy to patients with renal insufficiency. For example, sometimes patients with diabetes, the steroids that we give with the chemotherapy makes it difficult. Sometimes patients are unable to tolerate the pemetrexed also because of renal insufficiency.