Consolidation Therapy for Locally Advanced NSCLC - Episode 3
Julie Brahmer, MD:Durvalumab (Imfinzi) is an antibody that was developed to block the PD-1 pathway. It blocks this by binding to PD-L1 on the tumor cell, as well as other cells that express PD-L1, and that is the mechanism of action. By blocking the PD-1 pathway, it allows the immune system to actually remain activated and able to attack their cancer. Basically what we’re doing is taking the brakes off the immune system. The PD-1 pathway is just 1 pathway that our body uses to control inflammation and control the immune system. Tumors can block that pathway, and by blocking that pathway with an antibody like durvalumab, it again allows the immune system to remain activated and attack the cancer.
The reason why patients will benefit from receiving durvalumab after responding to concurrent chemotherapy and radiation is really the improvement in progression-free survival, as well as overall survival. We believe that durvalumab allows a systemic treatment and also cuts down the chance of patients’ developing metastasis later on, including…a decrease in the occurrence of brain metastasis in those patients who were treated with durvalumab after chemotherapy and radiation therapy as well.
Durvalumab side effects are really based on its mechanism of action. If we’re trying to take the brakes off the immune system, we know that the immune system, while we want it to be directed toward the tumor, can be directed toward normal tissues as well. I always say that this drug can cause side effects ending in-itis, inflammation of any organ system. However, significant side effects that cause you to stop treatment are not very common. That ranges in the 10% to a maximum of 16%.
In general, we do expect fatigue as a side effect of durvalumab. Potentially cough, if it’s related to respiratory symptoms. In general, this drug is very easy to tolerate, and the chance of side effects did not seem to be that much significantly different compared with observation. Now, certainly inflammatory, serious side effects, particularly pneumonitis. Pneumonitis can occur after radiation therapy, called radiation pneumonitis, but durvalumab can also cause pneumonitis, based on its immune mechanism of action. Now, there was not that much difference in the pneumonitis rate between the placebo arm versus durvalumab arm, but roughly that was about 5% to 10% difference, or increase, if you received durvalumab. In general, it was not that significantly different. In my mind, I was surprised that there was not that much difference, but when you’re treating with these types of drugs, you do have to be aware that patients can develop any inflammatory symptoms, and it’s something that you need to continue to routinely monitor for.
For patients receiving consolidative durvalumab, the general side effects compared with observation are not that much different, particularly significant side effects. The grade 3 and 4 side effect rate was approximately 30% in those patients who received durvalumab versus approximately 26% in those patients who were followed and treated with placebo. In general, durvalumab does not seem to add a huge amount of side effects after concurrent chemotherapy and radiation therapy, but certainly you do have to monitor patients for inflammation and immune-related toxicities.
Transcript edited for clarity.
Case: A 59-year-old Woman With Locally Advanced NSCLC