Camille Hertzka Addresses 5-Year PACIFIC Trial Findings, Future Ambitions for Durvalumab

Updated findings of the PACIFIC trial showed an overall survival (OS) rate of 43% after 5 years of treatment with durvalumab, a promising trend that will continue to be investigated in future clinical trials, said Camille Hertzka, vice president and head of Oncology, US Medical, AstraZeneca.

Transcript

As you report 5-year data on PACIFIC, what percentage of stage III NSCLC patients are receiving the regimen of concurrent chemotherapy followed by durvalumab?

What is really interesting is we've seen from the very beginning of the first presentation, and after the approval, really a lot of enthusiasm around this data. And we see now that approximately a little bit over actually 70% of patients are currently being treated with the PACIFIC regimen.

Updated results on subgroups will be reported at a later date, but OS [overall survival] data suggests favorable outcomes for several patient groups. Do the subgroup analyses generally hold up?

I think here, let me start first with what is the overall benefit that we see in the study. And I think that's probably where we need to start. In the primary analysis, we reported a couple of years ago, an improvement from of PFS [progression-free survival] as well as OS. During these analyses at ASCO, we present a 5-year follow up, which is a critically important milestone when you think about lung cancer, and lung cancer with unresectable stage III.

Here, what we reported was that the patients included in this study and treated with durvalumab had a rate of 43% of patients being alive 5 years later, which is really significant, especially for this disease. If you look on top of this, which is to me really extremely important to consider, is a number of patients who have not progressed during these years. And we can see that we have one-third of patients who are treated with durvalumab, who at 5 years were still progression-free with durvalumab.

Keeping in mind, they have been treated for a year with durvalumab after chemo radiation, which means that for this one sort of patient, they have been free of treatments and free of progression for 4 years. So, it's really significant for patients. Now, that it is a preliminary analysis, where we had power to demonstrate results into the primary endpoint.

If we look at the subgroup analysis, it has been really consistent over time that the benefits were reported and observed across the different subgroups. What we've seen from the very beginning was always this tendency of having women, patients who are younger, or patients with earlier stage–there’s a potential slightly better benefit, but it's very difficult to say if it's a better benefit or if it's just a prognostic of these patients. I think that's another important one.

When you look across studies in lung cancer, you will always, always see that women have a slightly better prognosis than men–you would always see that younger patients would have a better prognosis. So, I think when we look at these subgroups, it's important to consider what is predictive and what is prognostic. From what we've learned, there was nothing that really stood out that was a surprise. And it's consistent over time, nothing really changed at the 4-year or 5-year mark.

Does the decline in the OS rate between the 4-year and 5-year mark suggest the need for more treatment options for these patients?

When we look at the follow-up from as the first analysis to this later analysis, we see that actually it's very consistent and very stable over time. We've seen that, as I mentioned previously, the 5-year OS rate is 43%, which is relatively high when we think about lung cancer and when we think about the outcome of these patients in general. That would be probably the key takeaway that we have to take from the study.

There are very few events observed when get to tail of the curve, but what is important is, again, if you put your shoes in the shoes of all these patients–I said, more than 70% of patients are treated today with the PACIFIC regimen–what I see is actually this tail on the curve. And they see they might be one of them.

So, I think in terms of what it means, really, it means so much for patients. It means so much for physicians who have taken the decision to treat their patients with this specific regimen. With that, the important thing that you're asking is, can we do more? And I would say yes, we can always do more. And we want to do more.

This study has been really the first one raising the bar, and has given us so much energy to do more. We are studying different regimens. We have a study that you might know about, which is called PACIFIC-2, which is looking at durvalumab with chemo radiation at the same time instead of a sequence. And there are some other investigations in this setting. Because now we want to raise the bar even further.

We have 43% of patients being alive at 5 years. That's great, but we're aiming for 100%. That's a bold ambition, but that’s ambition we have, we want to eliminate cancer as a cause of death. PACIFIC told us we can raise the bar once, we will raise the bar another time. We'll see how long it will take, but that's the ambition we have. So yes, for your question, we need to do more and we are doing more.

Do the 5-year data support new screening guidelines that will call for screening patients for lung cancer at earlier ages? What can be done to boost screenings rates?

That's actually a really, really good question. Anything which is around screening is extremely important. To me the priority at this stage is really that we need to get all patients who should be screened to be screened. So, that is a first step.

We see so many patients, and especially underserved, medically underserved patient populations who are not doing the screening as they should. We see so many smokers who feel that oh, well, they don't want to hear about bad news so they will wait a little bit longer. You know how long is associated sometimes with this fear of feeling guilty that they did something.

So, it's really important that we raise awareness even further on the importance of screening in general. And so, what can we do? Raise awareness, make noise, tell everybody how important it is to do screening because of the impact it can have. And PACIFIC is a way to tell the story of what an impact it can make, because if you're not treated early, you will have a late-stage disease and the outcomes will be totally different.

I don't think the 5-year milestone is the main point. I think PACIFIC in general, plus all the other studies. I will mention just ADAURA, which was presented last year with osimertinib in even earlier stage. It is another very important milestone.

The advance we are making in the early stage is going to be impactful even further if more patients are being diagnosed earlier. So, we need to do everything to get a patient who should be screened earlier, and beyond lung cancer, I have to say. And just maybe one thing to add, there are a lot of technologies that are being assessed to actually improve screening rates, improve detection of early cancer, and I think that is a very exciting path moving forward.

Reference

Spigel D. Faivre-Finn C, Gray JE, et al. Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: An update from the PACIFIC trial. J Clin Oncol 2021;39:(suppl 15; abstr 8511). doi:10.1200/JCO.2021.39.15_suppl.8511