Clinical Cases in Lung Cancer - Episode 3

Case 1: IMpower133 Trial in Small Cell Lung Cancer

Edward Kim, MD: These are the NCCN Guidelines. You can see here that we’ve got several category 1 recommendations. You see that we’ve got combinations of chemotherapy with atezolizumab-durvalumab, with both carboplatin and cisplatin. Then the others are more of the older regimens, the backbone of platinum plus etoposide and then platinum plus irinotecan, which got a lot of momentum in the Japan but not as much in the United States, and probably deservedly so. This is IMpower133. This was a carboplatin-etoposide with or without atezolizumab for extensive-stage small cell lung cancer. Atezolizumab is an immunotherapy that is used in several other areas. The trial design was here with a primary end point of overall survival and PFS. It was the triplet versus the doublet with a placebo-controlled aspect. You receive 4 cycles of therapy, and then either had placebo or atezolizumab as maintenance therapy until follow-up progression. There was a PCI that was allowed but it was based on the standard of care that were done. You can see there was no biomarker really assessed as part of the eligibility in the treatment here. These are the survival curves, PFS and OS. As you can see, the median survival was improved by 2 months, 12.3 vs 10.3, with a 1-year survival of over 50%. Those are better than historical controls and were statistically significant. Then there was an updated overall survival close to 23 months, and you can see that effect has continued with a hazard ratio, a P value, and an 18-month survival of 34%. Here, we can see the IMpower133 response rates with atezolizumab. You can see that although we do have usually high responses in small cell with chemotherapy, both of these performed well in the 60% range. There was also stable disease that was very similar, but again, we did see an effect with the atezolizumab group with the added immunotherapy.

Chemotherapy-related adverse effects and immunotherapy-related adverse effects are things that we’re always cognizant of. Again, when you look at atezolizumab you’re going to expect to see more of these I/O related events. The overall grade 3/4 toxicities were very low, and that’s been our experience: We do see some severe toxicities but not as many. For instance, my nurse practitioner worked in melanoma for a couple of years and came over to work with me. She was really sacred when we started treating patients with I/O and weren’t doing UAs every week and getting thyroid function tests every week. I said, “No, that’s the way we did them in lung.” She said, “Are you sure?” You know, because she was coming from that melanoma area. Sure enough, that’s how it was, and we see the adverse effects can vary among tumor types with these I/Os.

Transcript edited for clarity.