Mark Socinski, MD: Kristin, I want to get your opinion. In the design of these trials we continue immunotherapy as maintenance. The 2 questions we used to address when we used to give 4 to 6 cycles of platinum/etoposide was A) is there a role for PCI [prophylactic cranial irradiation] in extensive stage disease, and B) is there any role for thoracic radiotherapy in this setting? I’m going to ask you that question first, and then if there are selected patients for which you would consider either, how do you integrate that when you’re giving maintenance immunotherapy?
Kristin Higgins, MD: That’s a great question. Radiation oncologists now are wondering how PCI and consolidated thoracic radiation fit in with the results of the CASPIAN and IMpower133 trials. For PCI in the extensive stage setting, radiation oncologists have stopped recommending it due to the conflicting data. The trial led by [Ben] Slotman, [MD, PhD,] and the Japanese trial showed opposite results with improved survival with PCI given in patients who don’t get routine MRIs of the brain. The Japanese trial showed that there was not a survival benefit if we give surveillance to patients with extensive stage small cell lung cancer with q3 [every 3] month MRI. We’ve seen a shift in radiation oncology with not recommending PCI in patients with extensive stage small cell [lung cancer].
In IMpower133 only about 10% of patients received PCI, and in the CASPIAN trial PCI was allowed on the control arm, but not the experimental arm. We didn’t see any worrisome toxicity in the patients who did receive PCI in the Impower133 trial. But with PCI there is significant toxicity, and as a field, we’re trying to potentially move away from PCI. There are more trials now addressing MR [magnetic resonance] surveillance in both the limited stage and the extensive stage small cell population. The SWOG cooperative group is running the MAVERICK trial, for example, that will help answer this question. When patients do get PCI in extensive stage, there's also a trial run through NRG [Oncology], CC003, which is giving PCI with hippocampal sparing, which carves out the part of the brain that is responsible for creating memories to try to reduce cognitive changes. So as a field, we’re leaning away from PCI in this patient population and that’s where we stand now. I hope the SWOG trial gets completed. I think it’s a great trial, and I would encourage people to enroll patients to answer this question when it comes to PCI.
In terms of consolidated radiation, patients weren't allowed to get thoracic radiation on either of these trials. We do know now we have some safety data for the combination of thoracic radiation and immune checkpoint inhibitors, and there's not worrisome toxicity. The role of consolidation radiation to the chest and to metastatic sites is going to be evaluated in an NRG trial, NRG-LU007, which will activate probably late summer. I look forward to putting patients on that trial. Right now, I would say we’re giving thoracic radiation on a case-by-case basis in some patients who have had a great response and have a small amount of residual disease. We’re doing so cautiously, because again, there are a lot of unanswered questions. What dose do we go to? How do you integrate it from a timing standpoint? And this is a data-free zone. I think we’re best to put patients on NRG-LU007 to answer the question in a scientific way.
Mark Socinski, MD: There was a suggestion from a very old trial published in the late 1990s, an Eastern European trial, that suggested in those patients who have a great response, maybe you could get some mileage out of thoracic radiotherapy, and as well with the follow-up Slotman trial. Still controversial, we still think about it and talk about it, but I’m glad you’re doing NRG-LU007 to help bring some more clarity to it.
Transcript Edited for Clarity