Reactions to the PACIFIC Trial in Stage III NSCLC

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Mark A. Socinski, MD: I think we would also all agree that 1 of the landmark trials that’s changed the standard of care in the past year or so has been…first, we saw PFS [progression-free survival] results from PACIFIC. And then in Toronto last September, we saw the overall survival data. Ticiana, could you briefly review the PACIFIC trial? Then we’ll have a discussion about that. I know Corey has some thoughts about that.

Ticiana A. Leal, MD: The PACIFIC trial looked at the question of using immunotherapy in the consolidation setting. This was a phase III trial that looked at randomizing patients 2:1 to durvalumab, which is a PD-L1 [programmed death-ligand 1] inhibitor, versus placebo after completion of chemoradiation if patients did not have any evidence of progression. In that study, patients went on to receive durvalumab versus placebo at 1 to 42 days after completion of chemoradiation, and they received durvalumab every 2 weeks for a total of 12 months. And then, similarly, in the placebo arm, they received it every 2 weeks for 12 months. That was a positive study. The primary endpoint of progression-free survival, there was an 11-month advantage of durvalumab over placebo. And then, subsequently, we saw confirmation of that with the overall survival benefit.

Most recently, we’re going to be seeing the 3-year overall survival, which maintains that same benefit that we saw in the publication in the New England Journal of Medicine. So this is definitely practice-changing. The treatment was very well tolerated. There weren’t any major toxicities or increased signals.

Mark A. Socinski, MD: No surprises.

Ticiana A. Leal, MD: No surprises.

Mark A. Socinski, MD: Kristin, what is your perspective as a radiation oncologist? And what do you say to patients during the treatment, and to help get patients through, and those sort of things?

Kristin Higgins, MD: I think with the PACIFIC study, our management of our stage III patients requires more close coordination with the medical oncology and radiation oncology teams. We need to make sure that we’re managing the adverse effects very well, especially in the critical last few weeks of treatment, such that those high-grade toxicities are resolved and they can get on immunotherapy, as was done in the PACIFIC trial.

Of note, for the PACIFIC study, there was no radiation QA [quality assurance]. Patients are registered after radiation was given, so it’s impossible to really dive in and interrogate the dose that patients got in terms of lung dosimetry and whatnot. It is what it is. I’d like to have that data, we just don’t.

Corey J. Langer, MD: Nor do we have data on baseline PETs [positron emission tomographies]. I think at least in North America, and probably most of Western Europe and East Asia, PET is part of the standard work-up. We will frequently, even if we’ve had a baseline PET, get PET as part of the simulation. So we’ll know whether there might be occult metastatic disease that was not built into the trial.

There’s a certain amount of attrition that would have also occurred in this trial. Remember that the randomization occurred after the completion of chemoradiation with 1 or 2 exceptions. The START trial looked at a vaccine. Virtually all other trials have generally looked at outcomes from the get-go, or from the point that chemoradiation has started. So it’s very hard to naturally compare the results of this trial to some of the older trials. Finally, the control arm, even though the survival overall looks quite promising, the median PFS was actually quite short—about 5.6 months. Not that we do that much better, but it’s typically 10 months, 11 months, 12 months, and not half of that. We have data on sites of progression and the fact that it was lowered across the board, including the brain. We don’t actually have data on patterns of failure, or first sites of failure, which are hopefully going to be looked at.

So I had a lot of reservations about this trial on that basis, but survival trumps everything, and the survival advantage is significant. It’s clinically meaningful. At 3 years, it’s holding up. Frankly, the control arm is doing as well or better than any other trial. The median has not been reached at this point.

Transcript Edited for Clarity