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ESMO 2025 | Enhancing survivorship and long-term management of ALK+ NSCLC
Sanjay Popat, MBBS, FRCP, PhD, Royal Marsden Hospital, London, UK, highlights the importance of considering survivorship and long-term management when treating patients with ALK-positive metastatic non-small cell lung cancer (NSCLC). Optimizing patient experience, particularly when using lorlatinib as a first-line treatment is necessary, by actively managing adverse events. Data from the CROWN trial (NCT03052608) indicate dose reduction due to adverse events does not impact efficacy. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
So when we are treating our patients with ALK-positive metastatic non-small cell lung cancer, we need to be thinking now in terms of survivorship and long-term management. Now, when we have the patient with ALK-positive lung cancer, it’s not very clear what their individual prognosis will be, but we know that there are some good prognostic factors and some poor prognostic factors...
So when we are treating our patients with ALK-positive metastatic non-small cell lung cancer, we need to be thinking now in terms of survivorship and long-term management. Now, when we have the patient with ALK-positive lung cancer, it’s not very clear what their individual prognosis will be, but we know that there are some good prognostic factors and some poor prognostic factors. If we know the patient has a TP53 mutation, that tends to suggest a prognosis, but still not guaranteed. Patients can still do very well with the TP53 mutation. Similarly, in England, for example, we have a national ctDNA programme, so we know whether the patients are shedding ctDNA at baseline or not. Patients that are not shedding ctDNA at baseline have a markedly improved prognosis compared to those that are shedding ctDNA at the time of presentation. Many of us are now using lorlatinib first line on the basis of the CROWN trial. This trial was presented at ASCO just over a year ago. The five-year update, I should say, was presented at ASCO over a year ago, demonstrating a remarkable progression-free survival at five years. And so that means if we are using lorlatinib up front, we have to be optimizing the patient experience during that time frame. We’ve now got nice approval to be using lorlatinib in the first-line setting. And if we do want to ensure that we are using lorlatinib appropriately, we have to actively manage the adverse events that patients will get. Patients will get some form of lipid, dyslipidemia, so we need to ensure that the lipids are well managed. They may or may not get neurocognitive and mood effects. We have to bring in the caregivers into the consultations to ensure that we are picking up these adverse events when they occur, because patients may not have insight into these issues. We shouldn’t be too scared of dose reducing if patients have adverse events, because we’ve got very good data from CROWN showing that patients that had dose reductions due to adverse events had no impact on efficacy at all. So we’re in a new area, I think, with ALK-positive lung cancer, with the NHS approval and NICE approval for lorlatinib in the first-line setting and optimising the patient experience through active management of adverse events is really key to making sure that we get patients through this.
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