Durvalumab Approval Redefines Resectable NSCLC Treatment Strategies

Earlier this year, the FDA approved durvalumab (Imfinzi; AstraZeneca) in combination with chemotherapy for adult patients with resectable early-stage (IIA-IIIB) non–small cell lung cancer (NSCLC) without EGFR mutations or ALK rearrangements. The approval was based on positive results from the phase 3 AEGEAN trial, which demonstrated a 32% reduction in the risk of recurrence, progression, or death compared with chemotherapy alone.

In this interview, Martin Dietrich, MD, PhD, thoracic oncologist with The US Oncology Network and Cancer Care Centers of Brevard, discusses durvalumab’s transformative impact on NSCLC treatment strategies, its use in the curative intent setting, and how oncologists can best integrate this therapy into their practice.

Transcript

What does this approval add to the treatment space for resectable NSCLC?

The approval of perioperative durvalumab in the AEGEAN trial is really an augmentation of what durvalumab already has provided to the lung cancer space. We've seen, obviously, great use in non–small cell lung cancer. The first signature indication was the consolidated durvalumab after chemotherapy and radiation without progression; [we are] seeing some very nice long-term, durable responses with a positive overall survival benefit. A second indication in non–small cell lung cancer [is] in combination with tremelimumab as a dual immunotherapy. But I think the most impactful use of durvalumab is in the curative intent setting, where we really move patients into a novel opportunity for treatment.

There are a couple of factors to consider. Obviously, the lessons we learned about biomarkers apply here as well, but what we've seen is that the patient factors do matter, and it does seem that there's a tremendous amount of improvement in the depth of responses. We've seen a very high level, almost 1 in 4 patients here with complete pathological responses—something that we don't see in the metastatic setting. And the reasons for that are not quite clear. Is it because the patient's immune system is still stronger? Is it a nutritional situation? Are there biological factors that may be playing a role? But it really has morphed into being the standard of care approach for resectable non–small cell lung cancer and eventually, hopefully, also for unresectable non–small cell lung cancer with an opportunity for conversion, but that wasn't the question in the AEGEAN trial. For us, the use of durvalumab has now substantially expanded. It was the first immunotherapy that we used in a curative intent setting, and now it is not only in the postradiation space, but in essence, the entire entity of surgical cases that are being utilized.

We don't have any head-to-head studies comparing adjuvant vs neoadjuvant or perioperative approaches, but it's quite clear from the data that perioperative is favorable. There are a lot of lessons biologically that we learn. We learn a lot about the prognostication of the tumor and we have opportunities and trials, and we're working very diligently on this as well for patients that don't have pathological complete responses. We're really trying to make this our standard of care and use chemotherapy and adjuvant immunotherapy only for cases that haven't been preoperatively identified as in need of systemic therapy. Sometimes we see these incidental lymph node positivities or other factors that may be playing a role. But for the standard patient who comes in through the door, perioperative approaches like we have in the AEGEAN trial with durvalumab [are] really the standard of care.

Have you noticed an increase in durvalumab uptake since this approval?

The arrival of durvalumab in the perioperative space has 2 hurdles. One is obviously it's a new indication, so we have to make sure that there's an awareness. And the second step is, we're really changing the way we're approaching early-stage resectable lung cancer, and there are obviously many multidisciplinary stakeholders that are involved. We have begun to shift this into the right direction of perioperative therapies, and it is a discussion with the surgeons. It's an understanding of the patient that the delay of surgery is not a bad thing, that we're really trying to utilize the presence of a tumor as a learning lesson and to understand the response patterns, but also as a priming field for the immunotherapy. It makes a lot of sense—PD-1/PD-L1 is an intratumoral communication between T lymphocytes and tumor cells. And if we resect the macroscopic tumor environment upfront, it's very hard to see how immune priming is supposed to happen, and I think that's reflected in the clinical data as well.

So, we have seen uptake. There's still a lot of way for improvement. I think we will work with our surgical colleagues to ensure that this is going to be moved forward and basically become the standard of care—like we do in breast cancer and colorectal cancer or in other cancers where neoadjuvant approaches are so successfully utilized, and I think that's going to be the same in non–small cell lung cancer.

The growth trajectory for durvalumab here [is] only helpful. It's obviously helpful to have an agent that has such a broad level of indications. We talked about the lung cancer indications, but there are certainly also changes that have happened in upper GI [gastrointestinal] tumors and hepatocellular carcinoma and biliary tract cancers, where durvalumab has had very good data. And we've seen perioperative data in bladder cancer. So the presence on formulary and the volume of a drug, the familiarity with the drug, all helps to ensure that durvalumab has a good start in the perioperative space of non–small cell lung cancer.

What should oncologists keep in mind when integrating durvalumab into the care of patients with resectable NSCLC?

I think that's a very important multidisciplinary question. When do we use durvalumab and how do we use it? As I mentioned, I think this is the gold standard for us to utilize perioperative immunotherapy, and durvalumab has really come in with very strong data in the AEGEAN trial. I think what's important to understand is not everything that can be resected should be resected upfront. I think there has to be sort of a "pumping the brake" kind of mechanism to ensure that the patient has the most use of immunotherapy.

We learn that immunotherapy can be helpful across the spectrum. We do see certain indications and utilizations where this seems to be particularly impactful, and I couldn't think of a higher impact than being a curative intent utilization of immunotherapy.