Oncology Frontier: 2023 ELCC released the results of a number of studies in lung cancer, which study are you most interested in, and why?
Dr Paz-Ares: I think this meeting is a particularly relevant meeting for continuous education, where the different and relevant aspects of lung cancer diagnosis, treatment and so on are reviewed and updated compared to standard-of-care. On top of that, some new data are typically presented. A good highlight for the current conference this year were some data updating the CHECKMATE-816 trial, showing more mature data on the benefit of chemotherapy plus nivolumab compared to chemotherapy as a neoadjuvant treatment in early stage non-small cell lung cancer. Importantly, it was suggested that an inflammatory signature may be predictive of benefit from this combination. There were some other interesting data updating the APPLE trial suggesting that third-generation TKIs like osimertinib are a better alternative compared to first-generation and then sequentially third-generation at time of progression even if using a liquid biopsy. Of course, there were updates of some other studies, including the presentation of novel phase III trials. There were two negative trials. The RESILIENT non-small cell lung cancer trial showed that the experimental drug, liposomal irinotecan, is not any better as compared to topotecan. And secondly, the CONTACT-01 trial with the addition of cabozantinib to atezolizumab does not improve prognosis, compared to standard-of-care in relapse non-small cell lung cancer.
Oncology Frontier: You present a poster about Phase I–III platform study evaluating multiple therapies in patients with biomarker-defined locally advanced, unresectable stage III non-small cell lung cancer(131TiP). Could you explain the background and study design of this study?
Dr Paz-Ares: This is a typical platform study of the stage 3 setting in patients with unresectable non-small cell lung cancer. Here the idea was that if you do genomic analysis of patients with unresectable stage 3 disease, you discover a number of patients with tumors with oncogenic mutations with some targets that can be treated with specific TKIs. For example, we believe that a number of patients will have amplifications that can be targetable, and in this trial, we have tried to identify alterations on driver genes such as ALK, ROS, RET and so on. After chemoradiation (the standard-of-care for stage 3), those patients could be offered a treatment with those specific inhibitors, as compared to the standard-of-care, which in this case would be durvalumab.
Oncology Frontier: Advanced non-small cell lung cancer patients with PD-L1≥50% are recommended to receive monotherapy with Immune checkpoint inhibitors (ICI) or ICI combined with chemotherapy. Would you recommend chemotherapy use in patients with high PD-L1 expression?
Dr Paz-Ares: At present, we know that both strategies – single agent checkpoint inhibitors or chemotherapy plus PD-1/PD-L1 inhibitors – are valid for patients whose tumors express PD-L1 in more than 50% of the cells. The question is which patients should receive IO (immunotherapy) alone and which patients should receive chemo-IO. In principle, we would prefer to have immunotherapy alone for most of our patients because it is a much easier treatment and less toxic compared to chemo-IO. However, we understand some patients are at risk of early progression or they need very rapid responses. For those patients, we tend to use chemo-IO. Those would, for example, be patients that need a very rapid response because they are very symptomatic. We also take other features into account. For example, those patients with low PD-L1 expression (meaning around 50% compared to high being 100%), or patients with low tumor mutation burden may be more likely to benefit from chemo-IO as compared to patients with high tumor mutation burden. Of course, we have to also take into account what the patient’s interest and opinion are.
Oncology Frontier: Does the efficacy of PD-1 inhibitors differ from that of PD-L1 inhibitors in extensive-stage small-cell lung cancer?
Dr Paz-Ares: At present, we have data from a number of trials suggesting PD-1 and PD-L1 inhibitors may be effective. Overall, that is my take, and it is likely there is not much difference between those agents. However, in Western countries, we typically have two drugs approved – atezolizumab and durvalumab – both being PD-L1 agents. The trial that used a PD-1 agent, pembrolizumab, was technically negative because they did not reach a statistically significant level of benefit, even though the results looked similar to the other trials. So, we tend to follow the labels, and it is our obligation at present to use durvalumab or atezolizumab. It must be said that there are some trials using PD-1 inhibitors in the Chinese population showing that some of those agents are also positives.
