How Prior Chemotherapy Impacts ICI Survival Outcomes in Patients With Lung Cancer

Jorge Nieva, MD, an associate professor of clinical medicine at the Keck School of Medicine of University of Southern California, discusses the results of the Impower010 study (NCT02486718), which evaluated the efficacy of the checkpoint inhibitor atezolizumab (Tecentriq) after chemotherapy for lung cancer compared to best supportive care. 

According to Nieva, immune checkpoint inhibitors (ICIs) can potentially provide long term survival benefits. However, patients who are cancer free are more likely to discontinue them due to toxicity, as a clinical benefit is not as clearly seen as with patients who are not cancer free. Patients with no active cancer are more likely to question treatment decision than those with active cancer, according to Nieva. 

One controversy Nieva expects is the cost associated with giving patients ICIs post chemotherapy.

The Difference Between Prior Chemotherapy and Chemotherapy-Naïve Patients With Lung Cancer When it Comes to ICI Use

0:08 | It's a good difference, and that we know that checkpoint inhibitors work better in the setting of chemotherapy treatment. And we've seen that repeatedly in stage 4 disease in the keynote trials and in a variety of others. So, I think that decision to say these had to be chemotherapy treated patients was a good one. It also allowed the sponsor of the study to select a fitter patient population, in that everyone was well enough to get chemotherapy. Pharmaceutical companies do a number of things in their clinical trial designs to be sure that the population being tested is very fit, because it reduces the number of confounding problems that the population might have.

The Potential Benefit of Giving Cancer-Free Patients ICIs

1:12 | I think particularly with the checkpoint inhibitors, because they do have the potential to provide long term survival, even in relapsed patients, there is a question of could everyone who benefited from these drugs have simply been salvaged by receiving checkpoint inhibitors at relapse? I think that's a very legitimate scientific question. And would raise the possibility that we could get similar impacts in terms of overall survival, with delayed rather than immediate therapy. But again, I don't think that's what the patients would want. But there are of course, cost implications to treating more patients with a drug than is absolutely necessary. And I think that's where the controversy is going to come from.

ICI Discontinuation Rate Differences in The Metastatic and Cancer-Free Setting

2:17 | We have a little bit of I would say, maybe a little higher discontinuation rate in this study than we see in the metastatic setting. And that's not at all unexpected these are all patients who are free of disease. And so, someone who has no active cancer is always questioning everything they're doing. Do I really need to do this? I think a lower level of toxicity will drive discontinuation in patients who have no measurable disease. Whereas people who have active disease, who can see clinical benefit, will tolerate a lot more toxicity and have a lower discontinuation rate. For someone with no measurable disease who doesn't really know if the drug is benefiting them or not, I think it takes a lower level of toxicity to make somebody decide I've had enough.