Updates in the Management of Extensive-Stage Small Cell Lung Cancer - Episode 5

The IMpower133 Trial in Extensive-Stage SCLC

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Dr Mark Socinski reviews the IMpower133 trial of first-line chemotherapy plus atezolizumab in extensive-stage small cell lung cancer.

Kristie Kahl: We’re going to switch to the IMpower133 trial. What was the design of the study, and what kind of patients were included?

Mark Socinski, MD: IMpower133 was a very simple design. It took the standard-of-care regimen of carboplatin and etoposide as the control arm. It was placebo controlled. It gave 4 cycles of treatment, which is my standard followed by placebo maintenance. The investigational arm simply added atezolizumab to the combination of carboplatin and etoposide, and it continued atezolizumab as maintenance therapy. It was done in patients with previously untreated extensive-stage small cell lung cancer. They had to have an ECOG performance status of 0 to 1. It was reflective of the types of patients we see in clinical practice on a week-by-week basis in our practices.

Kristie Kahl: What were the findings on the key efficacy end point?

Mark Socinski, MD: The key efficacy end point of interest is overall survival. There was a clear benefit. The median survival, which is not an end point I put a lot of emphasis on, was improved from approximately 10.3 months to 12.3 months—about 2-month difference in favor of adding atezolizumab. More important, the hazard ratio for overall survival was 0.7, about a 30% reduction in risk of death over time. There was about a 1-month difference in progression-free survival with a very similar hazard ratio. I believe it was 0.77. Interestingly, there was no significant difference in overall objective response rate. They were both around 60% to 65%, but that what’s we would think the going rate would be in this setting.

Those were the key efficacy end points. We also have some longer follow-up with 2-year survival, where the 2-year survival with the atezolizumab did exceed 20% in that trial. So these are important observations from IMpower133, and it led to the FDA approval of this agent and to this being incorporated in the NCCN [National Comprehensive Cancer Network] Guidelines, as well as other guidelines and pathways. It was a critically important trial and did change the standard of care in extensive-stage small cell lung cancer.

Kristie Kahl: Similarly, what were the safety findings?

Mark Socinski, MD: No surprises, actually. We’ve seen in a number of trials that combined standard chemotherapy with immunotherapy, both in small cell and non–small cell. The take-home message is that adding immunotherapy to standard chemotherapy doesn’t change the toxicity profile of the chemotherapy, and adding chemotherapy to the immunotherapy doesn’t change the toxicity profile of the immunotherapy. Because you’re using more drugs and these drugs are different, and the cytotoxic chemotherapy is different from the immunotherapy, you’re at risk of seeing more adverse effects. But in IMpower133, there were no surprises in terms of what you would have expected. It was a typical rate of immune-related adverse events, no different from we’ve seen in multiple other trials with atezolizumab. And the atezolizumab didn’t alter the typical chemotherapy-related toxicity we see with platinum etoposide in this population. So I have no concerns about the triplet regimen in this setting based on safety.

Transcript edited for clarity.