Global Perspectives on the PACIFIC Trial in NSCLC

Panelists: Benjamin P. Levy, MD, Sibley Memorial Hospital; Sanjay Popat, PhD, FRCP, Imperial College London; Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois; David Planchard, MD, PhD, Institut Gustave Roussy; Suresh S. Ramalingam, MD, Winship Cancer Institute


Benjamin P. Levy, MD: I’m curious how this will go. We’ve got a global panel here, and I think the unique perspectives here are important. How did this impact practice for you in Switzerland? Is this something that you’re routinely using already? Are you waiting for OS [overall survival] to come out before you can use it? How does this impact your everyday practice?

Solange Peters, MD, PhD: You will see during this discussion that in Switzerland, you’re very fortunate because you have access to many drugs through a registration program and also a compassionate program. We have had access to durvalumab since the PFS [progression-free survival] data, very soon after the publication in the New England Journal of Medicine. We have been starting to routinely deliver it.

I had the opportunity to write the editorial in the New England Journal of Medicine with a colleague. We just concluded that the magnitude of benefit, a little bit irrespective of survival at the time, was already supporting the delivery of durvalumab. We had started at the time. Now that we have the survival data, they even confirm what we are doing. I think that stage III disease is treated with a very heavy treatment, a multimodal treatment, in order to try to cure patients. We see cure in 15% or 20% of patients in the very good clinical trials, or even 30%. Whatever you can use that might increase the cure rates is really something you shouldn’t discuss.

Benjamin P. Levy, MD: I think we’ve been in a vacuum for a while in stage III disease without these drugs. I’m just curious about the French and United Kingdom experience. Is this something that you’re routinely using? Sanjay, you can start. Is this ready? Are you using it? And if not, when do you think you’ll be able to use it?

Sanjay Popat, PhD, FRCP: I think this is a game changer for stage III disease; it really is. The survival data really do cement the early data that we have in progression-free survival and time to distant metastatic disease. The regime is not routinely commissioned in the United Kingdom. However, there is a scheme such that the drug is made available. There has been a lot of reticence in taking this up in various parts of the United Kingdom, mainly around skepticism of progression-free survival and whether that would really translate to survival advantage. Now we’ve seen that survival advantage. And I really would encourage the rest of the United Kingdom community to follow this fantastic data that we have here and ensure that we are able to deliver concurrent chemotherapy with radiotherapy to this group of patients to ensure that we fit in the trial paradigm to allow durvalumab consolidation.

Benjamin P. Levy, MD: Very good. Any French perspective on this?

David Planchard, MD, PhD: I would say it is the same in France; that means we are quite convinced by the PFS, the magnitude of benefit in PFS, that has never been observed with all the previous trials until now. We were quite convinced, most of the oncologists in France. We have nowadays an expanded access program. That means all the patients with stage III disease who might receive immune treatment in consolidation with durvalumab have already received the treatment. This is in our standard. We routinely do this. We used to see the patient 2 weeks after chemotherapy and radiotherapy with a CT [computed tomography] scan evaluation to be sure there is no tumor evolution. Within that 4 weeks, the patient had already started durvalumab.

We were convinced. Nowadays, we are convinced by the overall survival. I think there is no doubt on this discussion. The only discussion that we will have is about biomarkers. It is about PD-L1 [programmed death-ligand 1] now because it will be restricted to the PD-L1–positive patient in Europe. I think it will be a big issue. We may have a discussion because we are not convinced that the PD-L1–negative patients do not benefit on this type of treatment. That’s why it will be something that we might discuss, how to treat the patient who is PD-L1–negative, because nowadays if we treat this patient it might also bring benefit in this population.

Benjamin P. Levy, MD: It’s interesting. I guess we’ll see with PD-L1. We’ll have a full paper very soon on this to see in the PD-L1–low disease, less than 1%, if that did benefit. Was the benefit there in those patients? The United States’ perspective has been interesting, and I’ll ask Ram to chime in here. The durvalumab consolidation story has changed things for us at Hopkins a little bit.  We were very much using concurrent chemoradiation followed by a couple of cycles of consolidation. Tucked in the appendix of this trial was the fact that the earlier you gave durvalumab to radiation, the better off these patients did. We’ve done away with the consolidation. Consolidation was not allowed in the PACIFIC trial. Roughly 25% or 30% got induction therapy. Ram, any thoughts on this? Has this changed the way you scan patients, the timing of the scan, or whether or not you give consolidation? How has this impacted you?

Suresh S. Ramalingam, MD: Ben, when I looked at the survival data from PACIFIC trial presented at this meeting, there were 2 things that struck my mind. One is the hazard ratio for overall survival. It was 0.68, trailing durvalumab. What that means for our patients is that there is a greater than 30% reduction in the risk of death as a result of receiving consolidation durvalumab. I think that’s unprecedented, as our colleagues here have pointed out.

The second thing is the question of what the median survival is. The good news is the median survival has not been reached for patients on the durvalumab arm, despite having a very robust followup. Obviously, that’s another exciting piece of news coming out of this. This really firms up the fact that durvalumab will now be considered the standard of care in stage III disease after chemoradiation therapy.

Now, consolidation therapy is something that we have tried in the past, even before the PACIFIC readout. I would say the enthusiasm for consolidation therapy was waning away piece-by-piece because of incremental evidence that it really doesn’t help. We can certainly say there is no proof that consolidation chemotherapy improves survival. We have a treatment that improves survival with durvalumab, so I think it’s an easy change in the paradigm when patients get chemoradiation. Once they recover from acute toxicities within the 4-to-6-week period, they would then go on to receive durvalumab.

Benjamin P. Levy, MD: Do you scan them after 1 to 2 weeks after they’re done with radiation to confirm stable disease and then move them on right away? Or do you hold off on a scan until 4 weeks just to get the maximum benefit from radiation?

Suresh S. Ramalingam, MD: Our multidisciplinary team believes that you’ve got to wait for a few weeks after chemoradiation before you get a good readout for the degree of benefit with chemoradiotherapy. Our first scan is typically around 4 weeks, and that’s also the time I would bring the patient in to start the consolidation durvalumab. That flows well in our clinic.

Transcript Edited for Clarity
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