Updated findings of the PACIFIC trial showed an overall survival (OS) rate of 43% after 5 years of treatment with durvalumab, which has . Physician’s Weekly spoke with Dr. Camille Hertzka, vice president and head of Oncology, US Medical, AstraZeneca, about the impact of those results, which were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, which was held virtually 4-10 June, 2021 [1].

The Phase 3 PACIFIC trial (NCT02125461) was a randomized, double-blinded, placebo-controlled, multi-center study (n=713) of durvalumab as a treatment in all-comer NSCLC patients, regardless of PD-L1 status, with unresectable, Stage 3 NSCLC whose disease had not progressed following concurrent platinum-based CRT. The primary endpoints of the trial were progression-free survival (PFS) and overall survival (OS), and secondary endpoints included landmark PFS and OS, objective response rate, and duration of response. Initial results were published in The New England Journal of Medicine , which already showed that the OS primary endpoint indicated a survival benefit for durvalumab [2].

The  updated survival analyses, based on 5-year data from PACIFIC, demonstrate robust and sustained OS in addition to durable PFS benefit with the PACIFIC regimen. The 60-month OS rates were 42.9% and 33.4% with durvalumab and placebo, respectively, and 60-month PFS rates were 33.1% and 19.0%, respectively.

Physician’s Weekly reached out to the US head of Medical Affairs Oncology at AstraZeneca, Dr. Camille Hertzka, for more information: “We were really excited to present the long-term PACIFIC follow-up data at ASCO this year, and I think what was very exciting was to see that we were able to bend the survival curve – so very impactful data for us. PACIFIC had consistent benefit from durvalumab with a long term follow-up, in unresectable Stage 3 lung cancer. Approximately a 70% of patients are currently being treated with the PACIFIC regimen.”

What about subgroup analyses?

“In the primary analysis, we reported an improvement from of PFS 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,  especially lung cancer with unresectable stage 3. These patients included in this study with durvalumab had a survival rate of 43% being alive 5 years later, which is really significant, especially for this disease with historically dismal survival. One extremely important additional fact to consider, is that one-third of patients who are treated with durvalumab remain progression-free at 5 years. This is astounding in context.”

“If we look at the subgroups of patients, it has been really consistent over time that the benefits were reported and observed across the different subgroups. Nothing really changed at the 4-year or 5-year mark; we still see women and younger patients doing better, but this is not unique for this trial or therapy.”

What does this mean for patients?

“The key takeaway is that 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 we have to take from the study. In terms of what it means, really, it means so much for patients. It likewise means so much for physicians who have taken the decision to treat their patients with this specific regimen. Of course, we continue to ask, can we do more? And I would say yes, we can always do more. We want to do more. We have 43% of patients being alive at 5 years. That’s great, but we’re aiming for 100%.
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PACIFIC told us we can raise the bar once, so 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 we need to start screening patients for lung cancer at earlier ages?

‘’We see so many patients, and especially medically underserved patient populations who are not getting  screened as they should. We see so many smokers who avoid being screened, and we need to address the stigma surrounding that basic precaution in the highest risk groups. PACIFIC is a testimonial to the impact of early interventiion, because if you’re not treated early, you will have a late-stage disease and the outcomes will be totally different. We need to raise awareness, make noise, reduce stigma, and tell everybody how important it is to do screening because of the impact it can have.”

Next steps?

“We are looking at many aspects, firstly; how can we improve this regimen in stage 3 unresectable lung cancer? PACIFIC 2 (NCT03519971) is looking at adding durvalumab at the same time as chemoradiation because what is happening is we know that a certain number of patients will relapse very early, and we also know that some patients will be too exhausted at the end of the chemoradiation to be able to receive durvalumab afterwards. Thus, by adding durvalumab at the same time as this regimen, we are seeing if we can increase the number of patients who can benefit from the overall treatment; we should results next year. The other study is LAURA (NCT03521154), with osimertinib which is going to look specifically at the EGFR segments. And then we have some other studies which are in early-stage durvalumab, such as the BR.31 study  (NCT02273375) that will look at adjuvant durvalumab in Stages 1-3 lung cancer that is resectable.”

 

  1. 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
  2. Antonia SJ, et al. N Engl J Med. 2018;379(24):2342-2350.