Advancing Stage III NSCLC Care Requires Personalized, Multidisciplinary Approach

Thomas A. Hensing, MD

The treatment of patients with stage III non—small cell lung cancer (NSCLC) requires a more personalized approach and newer technology, says Thomas A. Hensing, MD.

During his presentation at the 2017 OncLive^® State of the Science Summit^TM on Advanced Non—Small Cell Lung Cancer, Hensing, co-director of the Thoracic Oncology Program at NorthShore University HealthSystem, discussed proton-beam radiotherapy as a potentially impactful new technology in this setting.

OncLive: Please provide an overview of your talk.

Additionally, Hensing stressed that to avoid the one-size-fits-all approach that once hindered progress in stage IV disease management, modern technology and novel therapeutics not only need to be adopted, but must be managed by a multidisciplinary team to achieve optimal outcome for patients with stage III NSCLC.Hensing: Basically, the premise of my talk is that we have really had a prolonged plateau in outcomes for patients with stage III NSCLC. That is because we are approaching the management of stage III disease as we used to approach the management of stage IV disease, which is a sort of one-size-fits-all approach. We haven’t yet applied what we’ve learned in the management of stage IV disease into the stage III or curative setting, but that is starting to change.

We are certainly in need of new technology, and proton-beam radiotherapy fits the bill. However, the problem is that we still have limited access for patients because there is only a limited number of centers on board so far in the United States. It is an expensive technology and there is a challenge with getting insurance approvals for that. Therefore, it is not one that most patients will have access to. Clearly, there is still a learning curve and we are awaiting some prospective data before we can really know the role of proton-beam radiation. We need to achieve both local controls and better systemic control of the disease.

Do you have any insight to share on prospective studies in this space?

The bottom line is when we apply the current or older technology, we have not really moved the survival curve in this disease. But, as we start to move some of these newer agents and select patients better, we will see improved outcomes for patients with stage III disease.The most exciting prospective phase III study is the PACIFIC trial (durvalumab following concurrent chemoradiation in patients with stage III unresectable NSCLC). I remember sitting there as a fellow in the 1990s, looking at various randomized trials and looking at different doublets, trying to see survival curves when there was barely a difference between arms.

What challenges would you like to see addressed in the landscape in the next 5 to 10 years?

What do you hope community oncologists took away from your discussion?

The progression-free survival Kaplan-Meier curve [in PACIFIC] was the first time we saw a marked improvement in outcomes for patients with stage III disease. That’s what is exciting about [the PACIFIC trial]. It is the first time we have seen an advance of that magnitude—obviously, it is the interim analysis. However, it is certainly promising enough and the magnitude was significant enough that it is likely to translate to overall survival. It is exciting to apply this newer technology into the curative setting, and see that it may pay off. When we talk about stage III disease, the hallmark of it from a therapeutic standpoint is combination modalities. The population is [composed of] patients with unresectable disease and, here, we are combining chemotherapy and radiation. One of the clear messages from the published studies is that toxicity remains limiting in terms of local toxicity, particularly to normal structures. We are still seeing significant toxicity to the lungs, to the esophagus, and to the heart. The RTOG 0617 trial showed that those are some of the main factors that limit overall survival with current technologies. That is why we are in need of improved ability to reduced toxicity in this setting. That is why proton is a promising new technology; we just don't have enough prospective data to know if it will play a role.We are starting to see some improvement in patients with stage III disease. However, the crux of the issue is with combined modality therapy—we need to manage these patients with multidisciplinary teams as best as we can. That is not just something that can be done in academic centers, but it is something that can and should be done in community centers. We need to work together to manage these patients. The plans should be set upfront and prospectively with all of the folks who are caring for these patients all on the same page on how to manage them.

How do you see this technology advancing?

What ideas presented at this meeting have been particularly intriguing?

Our technologies are still limited; they are associated with limited toxicity and we need to do our best to get our patients through it. Therefore, that is the message for stage III disease—we need to have team-based care.To me, the most important thing is to take what we have learned in the metastatic setting and truly apply it to the early-stage curative setting. The key is that the fundamental difference is patient selection, which started in 2000 with stage IV disease and continues to today. We incorporated biomarkers to define subsets of patients who are going to benefit from a given technology. In the metastatic setting, the paradigm is: the right drug to the right patients at the right time. Moreover, I would like to see those technologies and patient selection strategies move into the curative setting. We want to incorporate these biomarkers so that we can pick the best treatment that is individualized for the patient based on their tumor biology.Particularly in the era of immunotherapy and molecularly-targeted therapy. The exciting thing is how we are taking these newer-generation drugs and moving them forward; they are having significant impacts. This is not only for length of life, but we are prolonging the period of time that the disease is controlled. From a patient perspective, if we can prevent or at least delay progression, that will really have an impact on the quality of life of our patients.