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ESMO 2022 | NSCLC trial updates at ESMO 2022: ADAURA, DESTINY-Lung02, KN189, KN407 & POSEIDON
Riyaz Shah, BSc(Hons), MBBS, FRCP, PhD, Kent Oncology Centre, Maidstone, UK, discusses trial updates presented at ESMO 2022 in non-small cell lung cancer (NSCLC). Updated results from ADAURA (NCT02511106) are highlighted, which demonstrate that following a further 2-year follow-up, disease-free survival benefit is sustained with osimertinib. Dr Shah also discusses findings from the Phase II DESTINY-Lung02 trial (NCT04644237) which evaluated trastuzumab deruxtecan, an antibody-drug conjugate, in patients with HER2-mutant metastatic NSCLC, and the potential for the use of HER2-targeting therapies for NSCLC in the UK. In immunotherapy, Dr Shah touches on updates results from KEYNOTE-189 (NCT02578680) and KEYNOTE-487 (NCT02775435), as well as findings from POSEIDON (NCT03164616), which investigated durvalumab +/- tremilimumab and chemotherapy as first-line therapy for patients with metastatic NSCLC. This interview took place at the European Society for Medical Oncology (ESMO) 2022 Congress in Paris, France.
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Transcript (edited for clarity)
Well, it’s been a fantastic meeting. There’ve been a lot of updates. As you know, lung cancer’s very, very complicated with lots of different molecular subtypes, so in terms of the areas that I think have been really exciting for me, there’ve been some areas of new data in molecularly targeted subtypes of lung cancer and then chemo-immunotherapy. For the molecularly subtyped aspects of lung cancer, I was very excited to see updated data from the ADAURA trial...
Well, it’s been a fantastic meeting. There’ve been a lot of updates. As you know, lung cancer’s very, very complicated with lots of different molecular subtypes, so in terms of the areas that I think have been really exciting for me, there’ve been some areas of new data in molecularly targeted subtypes of lung cancer and then chemo-immunotherapy. For the molecularly subtyped aspects of lung cancer, I was very excited to see updated data from the ADAURA trial. So this is adjuvant osimertinib for three years in patients who’ve had a completely resected EGFR-mutation-positive lung cancer, common mutations only. Patients had stage 1B to 3A disease, so that’s greater than three centimeters using the seventh edition, which was the staging system at the time of the trial. What we’re seeing is a very consistent result, very strong benefit and disease free survival, both in stage 2 to stage 3A and including stage 1B. The hazard ratios are perhaps a little bit worse, but not by much 0.2, 0.27.
The main issue with the study, well the ADAURA study, is they’ve shown data on neuroprotection, so a much lower incidence of the development of brain metastases in the patients having that. But what we’ve not seen is any mature overall survival data, and we’re having to have complex discussions with patients in clinic about whether they want or do not want to have that based on the relative immaturity of the data set. But in my clinical experience, when I’ve had these conversations with patients, the majority do go ahead and have treatment.
I think the other bit of information that we’re seeing is a slight sense because we’re now seeing what’s happening to the patients after they’ve had three years of osimertinib, and you get a slight sense that things are deteriorating, that the benefit is waning. You can see that at three, at three years, 36 months, the DFS curves start to change in their angle of attack if you like. There’s a slight worry here that maybe these are not curative adjuvant treatments, we’re just delaying metastatic disease. That’s the ADAURA study.
The other thing that was really exciting for me was the DESTINY study that was presented, which looked at trastuzumab deruxtecan, which is an antibody payload, ADC drug. This was a trial in HER2 mutations. So currently HER2 mutations are not on our national test directory in the UK, but I think they probably should be. We don’t have access to this drug, but the DESTINY study showed very clear activity with an overall response rate of well over 50% in patients that had advanced lung cancer previously treated and had HER2 mutations.
The other area that I think was really interesting for me was a five-year update, so mature survival data from the two landmark chemo IO studies that we use to judge a lot of our treatments in the UK. I’m talking here about KEYNOTE-189 and KEYNOTE-407, one trial in non-squamous and the other trial in squamous. Although there’s a lot of information in the granularity of the study, the top line figures are that about 18-19% of patients are alive at five years, which is fantastic. It’s just almost doubling of the number of people alive at five years. If you look at the landmarks and the people who are randomized to the non-IO arms, very exciting to see that. There was another update on a trial that doesn’t have five year survival yet called POSEIDEN, and that’s a really interesting trial looking at durvalumab, tremelimumab, chemotherapy or durvalumab chemotherapy. The main thing that I found interesting with that is their suggestion that KRAS-mutant lung cancers may benefit substantially from the combination of both durvalumab, tremelimumab, and chemotherapy.