Role of Adjuvant Therapy in Early Non-Small Cell Lung Cancer - Episode 6

Early Non-Small Cell Lung Cancer: The IMpower010 Trial

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An expert oncologist details the design, outcomes, and clinical implications of the IMpower010 trial.

Jessica Donington, M.D., MSCR: We had similar exciting news this past year. Dr. Dietrich, can you go into the Impower010 trial?

Martin Dietrich, M.D., Ph.D.: Yes, it’s a different form of trial but similar. It targets a different patient population. What we know is that if you have one mutation driving a cancer, like EGFR as Dr. Donington just explained in the ADAURA trial, oftentimes these cancer cells are not abnormal enough to appear well on the immune system’s radar. They’re actually very good markers for targeted therapy, and they’re also very good markers to decide against immunotherapy. Now the middle of the road lung cancer that doesn’t have an EGFR mutation is typically a strong candidate, I want to say, for immunotherapy. How does this happen and how does this work?

In general terms, if you have a cancer of any kind develop in the body, it is a little bit of a failure of the immune system to detect and eliminate these cancerous cells. That’s not a random event, but what happens is that the cancer cell tricks the T cell or the immune system’s main cell in this setting into believing that this is a benign, normal cell. There is a very strong interplay between your own body and your own body’s immune system to make sure that the immune system attacks bacteria, viruses and other kind of intrusions, but tries to avoid any sort of autoimmune reaction. There are two big kinds, one is the allergic type, and the other is the rheumatologic type of autoimmune disease, like a rheumatoid arthritis, lupus or others. Those can be quite cumbersome, and they have an impairment in this crosstalk between the immune system and the body cell. And here the cancer uses one of these chemical molecules called PD-L1 [programmed death-ligand 1] to essentially signal to the T cell that it is friendly, do not attack. It basically silences this immune system, and it abuses this highly important self-versus-foreign recognition in the immune system to stay undetected and grow.

What has been developed, and you can see this at the ending of MAB, or monoclonal antibody, of these medications, that we are using monoclonal antibodies that can target structures in the immune system to override these abnormal cancer-derived signals and restore T-cell activity. And this is where the IMpower010 trial was basically latching onto the adjuvant setting of lung cancer. Patients had undergone surgical resection, they were basically macroscopic disease free at the time of enrollment. They had chemotherapy and in this high-risk setting, chemotherapy was offered to everybody and reasonably so. Then patients were randomized to either best supportive care or observation, which was the standard of care at the time, versus the enrollment into immunotherapy application every three weeks in the adjuvant setting. And what we’ve seen is, the stronger the PD-L1 signaling that occurred in the tumor cells, and we measure them. We look at what is the number of tumor cells that are secreting PD-L1, which goes basically from 0% to 100%. The closer we got to 100%, the more useful this therapy was and was able to reduce the risk of recurrence and the delay of cancer in this setting.

Now, this was given for a year, this was shorter than the ADAURA trial, but because you’re not treating the cancer cell directly, you’re retreating the immune system to fight off cancer. The immune system has a memory, and this effect seemed to last long after the medication has been stopped. We are looking at a three-year landmark of analysis, and it was very clear that the absolute benefit reached after one year was the same benefit that we’ve seen after three years. So the early introduction of immunotherapy here is helpful. I do want to point out that we have been using atezolizumab, which was the investigational agent in this trial, for a long time in stage IV disease. And again, same pattern, what worked in stage IV, worked better in stage I, II and III. It’s not surprising that a healthier body produces a healthier immune response than somebody who is affected by stage IV cancer. Understanding molecular testing, and this is where our surgical colleagues do a beautiful job in providing, not only the resection of the tissue, but also the testing ground for us to understand what to recommend next.

I want to say EGFR and PD-L1 are the beginning of our testing. In fact, there are certain other markets that we would like to see as well, but those two are mandatory markings. This is a very recent update, and there’s a lot of information coming. When you’re getting treated, if you had a resection or you’re planning a resection, you should ask your health care provider what your PD-L1 status is, what your EGFR mutation status is, to basically nudge the direction of the discussion into a positive targeted- or immunotherapy-based approach. This always takes a bit of time to trickle into usage. If you are in a big academic center, this is probably adopted earlier than in some other settings. But you have a need to know these pieces of information because they can make all the difference for long-term outcomes. The journey begins with surgery, and surgery is certainly the only way of truly curing a disease. Without surgery, you wouldn’t have that opportunity.

But surgery is only the beginning; these additional steps are important. And while everybody should be considered for chemotherapy, the next steps are much more guided by these, what we call biomarkers or molecular features, of a cancer that tell us how a cancer ticks and how you can beat it by using its own weapons against it. That’s a fair summary and should be offered to every patient from stage I onward. There’s no question that these data pieces will change practice anywhere in the world in the next couple of months and years, and will get more and more refined. Insist on having this testing done, so that you can have the best possible outcomes.

Transcript edited for clarity.