Durvalumab for Unresectable Stage III NSCLC

Chaitali Nangia, MD, of the Patty and George Hoag Cancer Center, reacts to the significance of the 5-year overall survival data for the PACIFIC trial evaluating the use of durvalumab after chemoradiation as treatment for inoperable stage III non–small cell lung cancer.

Mark A. Socinski, MD: This was a fantastic discussion, very robust. I am going to transition [to a new topic] and ask Chaitali to give us her thoughts. We mentioned how far back the combination therapy goes in stage III disease—first induction and then concurrent, and then issues around consolidation. We established that concurrent chemoradiotherapy with platinum-based therapy was the standard of care but then we had a bit of a lull where nothing was happening until once again, moving immunotherapy into earlier stages of disease, in this case, stage III with a specific trial and then Chaitali at ASCO [the 2021 American Society of Clinical Oncology Annual Meeting], recently we saw the 5-year survival update, so give us your perspective on the PACIFIC trial. How that’s changed things and just your thoughts about it.

Chaitali Nangia, MD: To me, the PACIFIC trial was practice changing when it was approved in February 2018. Since then, the standard of care has been if [a patients] has a good performance status, irrespective of PD-1 status or histology, after completing concurrent chemotherapy radiation therapy (RT), and go on to durvalumab maintenance for about a year. We knew the data was initially presented for 2 years with excellent hazard ratios for OS [overall survival] and PFS [progression-free survival]. At ASCO, we saw an update for the 5-year OS and PFS and the numbers look pretty good. The hazard ratio was .72 for OS and PFS was even better, it was .55. If you look at what was the percentage of people with OS as 60, those numbers were very high and impressive with 42% of people still holding good at 5-year mark. There are no new safety concerns, so I think this effect remains the standard of care and the 5-year overall survival data is impressive and tells us how well people do in stage III unresectable situation.

Mark A. Socinski, MD: I was taught that when you have a positive phase 3 trial, you do the same thing in clinical practice that the trial did. One of the issues that always comes up is how important it is to receive the full year of durvalumab because if we look at the current situation, there are many patients who are dropping off and not getting the full year. Sometimes it’s for a good reason and sometimes it’s for not such a good reason. Your thoughts on the importance of the 1-year data, and do you share my opinion that it’s important in practice to do therapies how they showed benefit on the phase 3 trial?

Chaitali Nangia, MD: As much as possible I try to follow how it was done in the clinical trial, but the real-world experience is that once you are 6, 8, 9 months into it, it can get hot, just like how we saw with the mutation when your initial post radiation. It’s a similar situation that we all saw from the data from PACIFIC, that if you got it within the 2 weeks of radiation that those are the patients who did the best but how practical is that? How often do you actually get to get people started and completed in 2 weeks? It’s not hypothetical, so I do agree that as much as possible I would like to get patients to a 1-year mark. In practicality, how often does that happen? I would say I easily have a dropout rate something from 10% to 25% that don't get to the year.

Mark A. Socinski, MD: Does PDL-1 status mean anything to you in the stage III setting?

Chaitali Nangia, MD: If you are going to do this then you know it was. It was in the study it was irrespective of PD-1. They did do an exploratory subset analysis in which there was not much benefit if your PD-1 was less than 1% but having said that, there's caveats to that it was a subset analysis, so right now, irrespective of PD-1, I would offer them the maintenance durvalumab.

Mark A. Socinski, MD: And of course, the indication in the US is agnostic to PDL-1 status but with our European colleagues, they have a PDL-1 positive in 25%, correct? Correct me if I am wrong.

Chaitali Nangia, MD: That's correct.

Mark A. Socinski, MD: So, put a little bit of handcuffs in—that’s based on a unplanned, retrospective analysis that wasn’t protected by stratification. We know that not every patient had PDL-1 measure in the trial.

Chaitali Nangia, MD: Also important, 28% to 30% of people never had PD-1 measured, so you don't know what those numbers would look like if they were.


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