In an interview with <em>Targeted Oncology</em>, Kris, a medical oncologist and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center, discussed how the approval of durvalumab has changed the treatment landscape of NSCLC.
Mark G. Kris, MD
Based on the phase III PACIFIC trial, durvalumab (Imfinzi) received an approval in February 2018 from the FDA for patients with locally advanced, unresectable stage III nonsmall cell lung cancer (NSCLC). The approval has already begun to make an impact in the treatment of the disease, according to Mark G. Kris, MD.
In results from the trial, durvalumab demonstrated a progression-free benefit of 11.2 months compared with placebo in patients with locally advanced, unresectable stage III NSCLC who had not progressed following platinum-based chemotherapy concurrent with radiation therapy (16.8 vs 5.6 months; HR, 0.52; 95% CI, 0.42-0.65;P<.0001). Secondary endpoints, including objective response rate and duration of response, were also in favor of durvalumab. PACIFIC was the first phase III trial to test an immune checkpoint inhibitor as sequential treatment for this group of patients.
In an interview withTargeted Oncology, Kris, a medical oncologist and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center, discussed how the approval of durvalumab has changed the treatment landscape of NSCLC. He also highlighted other immunotherapies currently being studied in earlier stages of the disease.
TARGETED ONCOLOGY:Durvalumab was approved based on results from the PACIFIC trial. Can you discuss these results and why they were significant?
Kris:The PACIFIC trial compared standard chemotherapy and a radiation program in all patients that went on to get durvalumab after the conclusion of chemotherapy and radiation. What it showed was a clear improvement in progression-free survival and also a very comparable list of adverse effects for those patients that were randomized. That trial was something we had tried to accomplish for more than 2 decades, unsuccessfully, to improve on concurrent chemotherapy and radiation. The trial results are going to result in a big change in treatment, and really, they already have.
TARGETED ONCOLOGY:What impact does this approval have in the field of NSCLC?
Kris:Durvalumab is a major advance in the treatment of locally advanced lung cancers. For more than 2 decades, we have struggled to come up with a treatment that would improve outcomes beyond concurrent chemotherapy and radiation. All of our attempts proved unsuccessful, and sadly, some of them even led to a decrease in survival as we tried to do that. For the first time in over 2 decades, durvalumab has given us a treatment that we can give our patients that can further improve their survival and, ultimately, their cure rate over concurrent chemotherapy and radiation. It's truly a major advance.
TARGETED ONCOLOGY:What other treatment strategies are currently being investigated in stage III disease?
Kris:Stage III lung cancers are a unique group of patients. By definition, they have an advanced form of disease. They all have large tumors and [their disease has] spread to their lymph nodes, so they are at much greater risk of dying despite successful surgery and despite successful radiation treatments. They are a perfect example of a need for a multimodality care plan and a multimodal delivery of care. They're complicated, because every patient gets a definitive local therapy, either surgery or radiation, and they get a systemic therapy. It's an important group that is harder to treat, but the rewards are much greater, because not only can you improve the length of life, you also have the chance to cure patients. This gives us a great opportunity, but also great responsibility as well. We need to do everything we possibly can to lead to cure. That's really what our patients want. They want to be cured, and we should do everything we can to do it. How to do that is not simple, but the stage III space is the space where we can make that happen.
TARGETED ONCOLOGY:Can you discuss some of the currently ongoing trials with immunotherapy in earlier stages of lung cancer?
Kris:In patients that have complete removal of their cancer, there are 2 large thrusts of research today. One of them is in the neoadjuvant space. That is giving treatment before surgery. People that have locally advanced cancers face 2 risks: They face a risk of their cancer being uncontrolled at the site of origin, and, more importantly, they face a risk of metastatic spread. With these risks, treatments fail, which is why they need a systemic treatment and a local treatment.
Neoadjuvant therapy is a great way to approach these patients. It's been shown to be easier to give the drugs [to this group of patients]. The other part of it is that you can tell if that drug is helping the patient. Sometimes [you can tell] by a radiographic study or, at the time of surgery, the tumor can be removed and studied. You can tell how effective the treatment has been before the operation. You can use that information by studying the cells that remain after the initial treatment to decide what the next treatment is.
The other strategy is adjuvant therapy, where the cancer has been completely removed and, at the time of surgery, you find some characteristic that says it's likely to come back again and then you try to do something. But there's no way to tell if that treatment is helping today because we don't have another way in 2018 to reliably assess that the adjuvant treatment has worked.
Both strategies can be helpful. Both neoadjuvant and adjuvant therapies have been shown to increase the chance of cure. However, I think there have been many more factors favoring neoadjuvant therapy, but both are being studied.
TARGETED ONCOLOGY:What are the unanswered questions that still exist with regards to immunotherapy in lung cancer?
Kris:When it comes to immunotherapy in lung cancer, the big question that remains is how we can find patients who are going to benefit from it, and particularly patients who are going to have substantial benefit from it, and benefit to an extent that they don't require any other therapy. We have all seen patients with advanced cancer who have their cancer come under control and it disappears with just an immune treatment. If we could find those patients, we could make sure we give them the best immune treatment and not add on the burden of additional therapies, be it radiation, surgery, or chemotherapy. That is the biggest issue.
Also, for patients that are very unlikely to benefit from immune treatment, we can move on to things that have a chance of helping them, like chemotherapy, for example. That's the biggest need right now. We just don't have a test that's absolutely reliable right now.
Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III nonsmall-cell lung cancer.N Engl J Med.2017;377(20):1919-1929 doi: 10.1056/NEJMoa1709937.