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ONCAlert | Upfront Therapy for mRCC

NSCLC Stage III Unmet Needs and Practical Advice

Targeted Oncology
Published Online:1:37 PM, Fri February 15, 2019

Mark A. Socinski, MD: The PACIFIC trial has really changed the outlook for stage III patients. However, we still don’t have 100% cure rate in this particular setting. I think some of the unmet needs are trying to get a better definition of who gets benefit from immunotherapy. Are there patients in which PD-1 or PD-L1 inhibition isn’t enough? We have other checkpoint inhibitors, CTLA4 inhibitors.

Other targets are coming in clinical trials. How do you identify patients who may need either a different or more enhanced immunologic effect? How do we use targeted therapies in this population? I mentioned before about EGFR mutations. What’s the role of an EGFR TKI [tyrosine kinase inhibitor] in stage III disease? Those trials are ongoing. ALK-positive patients, ROS1-positive patients, and other subsets.

One of the challenges in studying these in stage III disease is that these are very uncommon to rare patients. We don’t have a lot of them, so it’s very difficult to study them. So I think that the unmet needs focus around how do we take everything we’ve learned in stage IV disease where we are clearly improving survival and translating that to stage III disease integrating targeted therapy, identifying patients beyond the biomarker of PD-L1 who may get greater benefit, those sorts of things. So there’s a lot of work to do. I think PACIFIC is a great kind of launching pad to get some kind of optimism and enthusiasm for studying these issues in stage III disease.

I think the practical advice for the practicing oncologist is the importance of accurate staging. So you identify patients with stage III disease. Most of the patients with stage III disease do have unresectable disease, so surgery doesn’t play a role. I think for the practicing clinician, they need to embrace the PACIFIC data. They have the opportunity to provide a patient with a higher cure rate and better long-term survival, that concurrent chemoradiotherapy, doing it well in the multidisciplinary setting. The medical oncologist needs to be hand-in-hand with the radiation oncologist. We have to work together as a team. You have to get the patient through concurrent chemoradiotherapy without missing any major part of their radiation or their chemotherapy… You have to use durvalumab within 6 weeks of completing radiation. You should be with your radiation oncologist. As a medical oncologist, you should be making sure that you have a comprehensive plan to get the patient through with minimal esophagitis, with minimal fatigue, with minimal myelosuppression, so that that patient going through very tough therapy with chemoradiation is fit and can recover from that within a week or two and be able to start immunotherapy, certainly within 6 weeks. But I like to start it as early as I possibly can in these patients.

And there are some data from the PACIFIC trial suggesting that if you start it earlier, within 2 weeks, that there might be greater benefit. So all things being equal, I like to start it as quickly as possible. But part of the ability to do that is you make sure that you manage the expected toxicities of chemoradiation. The most important one is esophagitis, that you manage that prospectively and aggressively and try to minimize any high-grade toxicities with regard to the esophagus, and let patients recover quickly so they can move on to immunotherapy.

Transcript edited for clarity.

Mark A. Socinski, MD: The PACIFIC trial has really changed the outlook for stage III patients. However, we still don’t have 100% cure rate in this particular setting. I think some of the unmet needs are trying to get a better definition of who gets benefit from immunotherapy. Are there patients in which PD-1 or PD-L1 inhibition isn’t enough? We have other checkpoint inhibitors, CTLA4 inhibitors.

Other targets are coming in clinical trials. How do you identify patients who may need either a different or more enhanced immunologic effect? How do we use targeted therapies in this population? I mentioned before about EGFR mutations. What’s the role of an EGFR TKI [tyrosine kinase inhibitor] in stage III disease? Those trials are ongoing. ALK-positive patients, ROS1-positive patients, and other subsets.

One of the challenges in studying these in stage III disease is that these are very uncommon to rare patients. We don’t have a lot of them, so it’s very difficult to study them. So I think that the unmet needs focus around how do we take everything we’ve learned in stage IV disease where we are clearly improving survival and translating that to stage III disease integrating targeted therapy, identifying patients beyond the biomarker of PD-L1 who may get greater benefit, those sorts of things. So there’s a lot of work to do. I think PACIFIC is a great kind of launching pad to get some kind of optimism and enthusiasm for studying these issues in stage III disease.

I think the practical advice for the practicing oncologist is the importance of accurate staging. So you identify patients with stage III disease. Most of the patients with stage III disease do have unresectable disease, so surgery doesn’t play a role. I think for the practicing clinician, they need to embrace the PACIFIC data. They have the opportunity to provide a patient with a higher cure rate and better long-term survival, that concurrent chemoradiotherapy, doing it well in the multidisciplinary setting. The medical oncologist needs to be hand-in-hand with the radiation oncologist. We have to work together as a team. You have to get the patient through concurrent chemoradiotherapy without missing any major part of their radiation or their chemotherapy… You have to use durvalumab within 6 weeks of completing radiation. You should be with your radiation oncologist. As a medical oncologist, you should be making sure that you have a comprehensive plan to get the patient through with minimal esophagitis, with minimal fatigue, with minimal myelosuppression, so that that patient going through very tough therapy with chemoradiation is fit and can recover from that within a week or two and be able to start immunotherapy, certainly within 6 weeks. But I like to start it as early as I possibly can in these patients.

And there are some data from the PACIFIC trial suggesting that if you start it earlier, within 2 weeks, that there might be greater benefit. So all things being equal, I like to start it as quickly as possible. But part of the ability to do that is you make sure that you manage the expected toxicities of chemoradiation. The most important one is esophagitis, that you manage that prospectively and aggressively and try to minimize any high-grade toxicities with regard to the esophagus, and let patients recover quickly so they can move on to immunotherapy.

Transcript edited for clarity.
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