Corey J. Langer, MD: Survival is important, but it makes no difference if the patient’s quality of life is dwindling in that period. The roughest thing is probably to have a patient live longer but more poorly because of toxicity or because the aftereffects of the cancer remain. A remarkable observation from the KEYNOTE-189 trial was that quality of life was preserved or stabilized for a much longer period on the combination arm compared to the control group. I believe the median was not reached versus about 7 or 8 months for the control group. Amongst those who actually had an improvement in quality of life at about 20 to 24 weeks, a borderline significant increase was seen again in the pembrolizumab arm. Not only are we maintaining quality of life, we actually see at some point during the course of treatment a relative advantage for pembrolizumab. That really is distinct from many other trials that have looked at quality of life in this setting.

Many of our patients fear that no matter what we do, their quality of life is going to be compromised. It’s really quite the opposite. Cancer itself, particularly advanced non—small cell lung cancer, will compromise a patient’s quality of life. If we can prevent deterioration in their typical symptoms of cough, chest pain, or shortness of breath, their quality of life will improve. Many of my patients are quite surprised by how much better they feel while they’re on treatment. If we do a good job controlling toxicity, the advantage remains. We’re not compromising that improvement in disease-related symptoms with treatment-related symptoms.

Vassiliki Papadimitrakopoulou, MD: A quality of life analysis was performed for KEYNOTE-189 looking at time to deterioration of symptoms. Despite the greater incidence of grade 3 to 5 adverse events, quality of life was maintained in the investigational arm for these patients demonstrating that there is overall benefit beyond response rate, progression-free survival, and overall survival.

Hossein Borghaei, DO: Quality of life for patients with advanced disease is of paramount significance. Patients don’t want to be spending their time in a hospital setting or in and out of a clinic for evaluation just because they’re getting treatment. Now, I think we’re fortunate that we practice in an era where we have not only very efficacious drugs but also well-tolerated drugs. I think it’s always important to keep in mind that grade 1/2 toxicities that we normally don’t concentrate on can in fact have an impact on patients’ quality of life when they become chronic. When I teach my Fellows, I always say, “Yes, 2 or 3 bouts of diarrhea a day might not elevate someone to require an intervention, but you can imagine if you have 2 or 3 bouts of diarrhea that’s unpredictable throughout the day? You don’t want to leave your house.” So, that does impact quality of life for sure.

With that in mind, the chemotherapy combination data—at least based on the units that we measure in terms of dyspnea or other factors—seem to suggest that a combination with pembrolizumab plus chemotherapy is actually better for symptom relief than the use of chemotherapy alone. Here we’re again in a fortunate setting where we can sit across from the patient and say, “Not only do I have a combination that’s very active that can help you live longer, but I also think we can manage your quality of life to be fairly decent because we have data that actually suggest certain symptoms actually improve more with the addition of immunotherapy as opposed to chemotherapy alone.” I think patients absolutely want to have a good quality of life. They want to be able to enjoy the time that they have with their families. They want to be active, productive. A lot of my patients still like to work, so combinations like this provide us with an opportunity to keep our patients doing what they want to do.

Transcript Edited for Clarity