ASCO 2021 | 5-year survival outcomes from the PACIFIC trial

Basically, what is being presented is the five-year update on a study called the PACIFIC trial. So this is a pivotal study that’s been previously reported, first in The New England Journal for an endpoint that was progression-free survival. And now here we are five years later with overall survival.

But just to back up a little bit, what was the study? So this was an important trial in unresectable, stage three, non-small cell lung cancer. This was a global study. The design was pretty simple. It took patients with any non-small cell histology, allow them to receive the standard of care in the world, which is combined modality, chemoradiotherapy, a platinum-based regimen, and then at the end of that completion, as long as patients were otherwise kind of well from that treatment and met eligibility criteria in terms of safety and organ function, they were then randomized to the PD-L1 inhibitor, durvalumab or placebo. And so that’s an important part of this trial, it was a placebo-controlled study.

And so what we saw in this study initially, was an improvement in progression-free survival and then ultimately in overall survival. And that has already led to a change in the standard of care in many places in the world, certainly in the United States, in terms of the treatment of stage three disease, unresectable disease. That is to say a patient comes in today with stage three unresectable cancer, non-small cell lung cancer, they would be treated with chemo radiotherapy followed by one year of durvalumab, because of those pivotal early results for PFS and OS.

So here we are now, presenting the five-year updated survival analysis and basically it supports the original conclusion, but also shows that patients continue to do well. So what is known in this update that’s being presented at this year’s annual meeting, is that durvalumab continues to have benefit for both PFS and OS, and specifically there’s a hazard ratio demonstrating a 28% reduction in the risk of death, and about a 45% reduction in the risk of progression or death, when you look at the intent to treat population.

I think what’s most impressive is that about 43% of patients under durvalumab are more alive at five years, compared with about 33%. So put that in perspective. About 43% alive at five years if you got durvalumab, and then the placebo group, that number is about 33%, and that’s kind of the take home message. If you looked at who’s alive and without evidence of progression, so that PFS landmark assessment at five years, that number for those groups respectively is 33% versus 19%. So again, 33% alive without progression at five years, compared with 19%. And that number, that 19% is the number that we’ve stuck with for many years, we’ve just known that about one in five of our patients at five years would be alive without disease progression. And now we know that number is 33% with durvalumab.

I guess the other important thing to mention is no new safety signals as you follow more patients out, so that’s encouraging. Also, when you look at the many subsets of patients by histology, other baseline demographic factors, there doesn’t appear to be one group or one factor, I say, that accounts for these benefits, whether you look at gender or age or performance status, et cetera, histology, patients all seem to benefit independently because of durvalumab.

So that’s the take home, I think, big finding. In research I think we like these five-year cutoffs. We saw similar kind of data obviously at four years, a year ago, and now five years is really kind of a big milestone I think, for not only the study, but obviously for patients.