In an interview with Targeted Oncology™, Eric S. Nadler, MD, discusses IMpower133’s real-world implication and the effects immunotherapy has had on the ES-SCLC space.
The IMpower133 trial (NCT02763579) helped to establish immunotherapy’s usefulness in extensive-stage small cell lung cancer (ES-SCLC). However, questions remain around atezolizumab’s (Tecentriq) real-world efficacy and uptake.
A retrospective analysis looked at 408 patients diagnosed with ES-SCLC between October 1, 2018 and December 31, 2019. Follow up was conducted through March 31, 2020. Data was collected using the US Oncology Network’s electronic health records data.
Of the 408 patients, 71.4% received immunotherapy plus chemotherapy and only 21.4% received chemotherapy alone. This shows that the uptick of results from IMpower133 results was almost instantaneous. Additionally, real-world efficacy results were found to be in line with the IMpower133 results.
In an interview with Targeted Oncology™, Eric S. Nadler, MD, the medical director of US Oncology Health Informatics and Internet Technology, discusses IMpower133’s real-world implication and the effects immunotherapy has had on the ES-SCLC space.
TARGETED ONCOLOGY™: Can you give me a brief overview of your retrospective on immunotherapy in non-small cell lung cancer?
NADLER: Basically, we wanted to study 2 things. We wanted to look at the adoption pattern of immunotherapy in the community after the publication and presentation of IMpower133. So, we wanted to see how quickly it would take doctors in a large community network, the largest community network, to actually begin to bring in immunotherapy into their practice. And, secondarily, to be honest, we wanted to look at the efficacy of it. We wanted to see if you extend it to real world patients. These patients tend to be sicker and older and have a lot more comorbidities. They don't have the same stringency of entry criterion when you offer that type of therapy in clinical trials, it’s very stringent which types of patients you're allowed to offer therapy to. But in the community, you can offer it to anybody you think is appropriate. So, that was a background of why we did it.
The dates of the study were between October 2018 through December 31, 2019. So, basically, the moment Impower133 was presented, even before it's FDA approved, for about an 18 month follow up. We looked at just under 350 patients who received that regimen. And once we audited the data, 267 were found to actually have chemo immunotherapy with atezolizumab. And we did have a competitor arm, just to kind of look at and engage it, and 23% had chemo alone.
One question that was kind of interesting, we did wonder how many were receiving their infusion in the frontline and inpatient setting, and it was 20%. A number of patients are sick when they have small cells, it's a very aggressive disease and you'd met them to the hospital in that first cycle is not always given with the immunotherapy, but they're received it on the second. The take home of this was the data mirrored Impower133, which was fascinating. So, it wasn't quite the same extended follow up. But our end points of PFS and duration of therapy, things that really track with the clinical efficacy of that regimen were basically spot on with Impower133, nearly identical in fact. The only thing that wasn't was the follow up. But the good thing or the interesting thing, was one quarter of the patients had a performance status of 3 or higher. So, patients who wouldn't have been on it. And other 16% weren't even documented. They may have been equally bad. They were a little bit older. Closer to 68 as opposed to the 63,64 that we see in the trials. And the number of them were actually significantly older. They had brain metastases that presumably were treated, but a much higher level of brain metastases at baseline. It was almost a quarter as opposed to the under 10% that was seen in Impower133. So, a lot of things that echoed a sicker patient population, more comorbidities more brain metastases, and yet the efficacy was similar. So, it was exciting that we could show that even as you put this regiment into more real-world patients, the efficacy was kind of unchecked and there wasn't any undue toxicity or early terminations that we could discern.
How was the retrospective conducted?
Everybody was included retrospectively through the database that we had. The database of US Oncology McKesson that was used us roughly 15% to 16% of the oncology patients in the United States. So, it's a huge database. Again, they were audited down because they couldn't have been on clinical trial, there are a number of things that we look through, where we actually just weed out the patients to make sure that the ones, we have been truly real world. So, they can't have other cancer diagnoses, can't have prostate cancer, or CLL. We don't put those in because it could confound it. But essentially, we clean it a little bit. But patients who were newly diagnosed anywhere within the network were put into that over that time. And that was a final number once we audited that we came up with.
What were the results of your study? Did you find anything shocking or particularly interesting?
I don't think there is anything shocking or surprising. It showed 2 things at the end of the day. It showed that it was readily adopted almost immediately, the majority of patients were getting chemo immunotherapy immediately from the publication and presentation of this data and its adoption. Some people think that it takes 18 months, sometimes even longer than that to funnel innovation to community physicians. But this actually shows that almost immediately, or at least the comfort of using immunotherapy in other diseases and in lung cancer must have been in embedded in the network, because as soon as it was FDA approved, it was adopted almost entirely throughout the network in a very short period of time. And then the second thing is, I would imagine that the data that was presented would echo real world findings. I didn't think that patients being a little bit old or those who had brain metastases or any of these other things, or a little worse projected survival would not be able to tolerate the addition of immunotherapy to it. So, the fact that it echoed the data we saw in Impower133 was not actually a surprising finding. I would have expected that. It was just nice that both of those things bore out.
I think it says that chemo immunotherapy is the standard of care in small cells. That was true before we did this study and it is true now. And it just is a piece that gives comfort to the practicing doctor that these types of innovations can be applied to their patients and not just those who are deemed eligible for clinical trial.