Potential Impact of Immune Checkpoint Inhibitors in Thymic Malignancies

Corey Langer, MD, Director of Thoracic Oncology, Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA, provides an overview on the potential for immune checkpoint inhibitors in the treatment of thymic malignancies, a topic he presented at the virtual 2022 Great Debates & Updates in Lung Cancers meeting.

In his presentation, Dr Langer discussed the current established treatments for thymic malignancies, the possibility of immune checkpoint inhibitors yielding responses in this population, and also addressed some of the treatment-related adverse events associated with immune checkpoint inhibitors.

Transcript:

Hello, I'm Corey Langer, the Director of Thoracic Oncology at the Abramson Cancer Center at the University of Pennsylvania. I had the privilege at the end of August of 2022 to co-chair the Great Debates & Updates in Lung Cancer meeting. It's done virtually with my colleague, Eddie Garon from L.A., and I was able to give a brief talk on thymic tumors.

I consider thymic malignancy to be one of the zebras of the thorax. It's a relatively rare tumor with just a smattering of cases each year in the United States, probably fewer than 1000 to 2000 early thymic tumors, that are confined just to the anterior mediastinal, highly curable with surgery, or if there's invasion into the pleura or the mediastinum, surgery plus radiation.

But more advanced tumors, those with the drop deposits in the pleura or more distant metastases are really in the province of systemic therapy. Intriguingly, the standard regimen has historically been a rather old combination of cyclophosphamide doxorubicin and platinum, which in the eighties and nineties generated response rates of 50% or higher, and as a result has remained the standard of care, or at least the standard of comparison. More recent data has looked at other combinations of paclitaxel, carboplatin, pemetrexed, either alone or with carboplatin, some of the multi-targeted kinase inhibitors such as sunitinib and other chemotherapy combinations such as gemcitabine and capecitabine, with comparable response rates, maybe a bit lower, but obviously much better tolerated.

More recently, at least in advanced disease, we've started looking at immunotherapy, and here it's a bit dicey. Thymoma is associated with paraneoplasia, which is often immune-based, or autoimmune myasthenia gravis, hypogammaglobulinemia, pure red cell aplasia, and other somewhat strange paraneoplastic syndromes.

In the early studies looking at immunotherapy single agents in this disease, while yielding responses, were often associated with significant, in some cases life-threatening, immune-mediated adverse events. It's a dicey approach, at least in pure thymoma. For thymic carcinomas, which are far less associated with immune-related paraneoplasia, the incidence of these immune-mediated toxicities seems to be a bit lower, but they can still occur, and we have to be very careful.

On the other hand, some of the responses realized with immunotherapy in this disease, particularly in chemorefractory patients, has been quite rewarding, so this is clearly a new area to look at. There are some reservations because of the toxicity, but as we've seen elsewhere in virtually every other solid tumor malignancy, particularly in lung cancer, bladder cancer, renal cancer, and of course, melanoma, there clearly is some activity with the immune checkpoint inhibitors.

Source:

Langer, C. Impact of CPIs on Thymic Malignancy. Presented at: Great Debates & Updates in Lung Cancers. Aug 24-26, 2022. Virtual.