Alessandra Curioni-Fontecedro is Professor of Oncology and responsible for the Translational Oncology Lab at the Center for Hematology and Oncology, University Hospital, Zurich, Switzerland. She is also a member of the faculty of the European School of Oncology (ESO).
- The true revolution in the treatment of lung cancer is immunotherapy, as we saw here at ESMO.
- If we look at the data on advanced non-small cell lung cancer (NSCLC) with metastases (stage IV) the median overall survival was 9 months before immunotherapy, and less than 5% survived more than 3 years. Now we have the data on immunotherapy at 5 years (given not as first-line but as a second, third, or even later line of treatment) showing an overall survival rate of 56%.
- In our lab, we evaluate new combinatorial treatments consisting of a combination of targeted therapies and chemotherapy to immune-checkpoint inhibitors in order to understand the underlying mechanism of action in mesothelioma and lung cancer. Many studies show that the response of immunotherapy plus chemotherapy, even without a real selection of patients (so independent from markers or from the PD-L1 status), is much higher than with chemotherapy alone.
- PD-L1 is actually considered an essential marker for the selection of patients in immunotherapy. PD-L1 is upregulated in many cancers and allows cancers to evade the host immune system. It is overexpressed in 50% of the patients with lung cancer and probably those are the ones who can be treated with immunotherapy alone, while the others, where the marker is not available, can be treated with a first-line combo therapy.
- Let’s talk about tolerability: the available data comparing patients undergoing immunotherapy and chemotherapy show that the first group tends to have a normal life during treatment instead of experiencing worsening, as often happens during chemotherapy.
- Innovation is coming also from the increased depth of analysis we can perform on a tumour: every day there are new markers that can be possible targets for treatments. There is also an evolution in terms of the number of treatments that will become available for the same target, and this helps us to fight resistance.
- Here at ESMO, Aurélien Brindel presented an interesting study on uncommon EGFR mutations in lung adenocarcinomas. By analysing EGFR mutations, they identified some uncommon ones in around 11% of patients. Those patients, treated with first-line chemotherapy have a better overall survival (27.7 vs 16.9 months) than those treated with targeted therapies as inhibitors of tyrosine kinase. It’s an example of how important it will be to profile patients and tumours in order to decide if a patient should receive, as first-line treatment, chemotherapy, targeted treatments, or immunotherapy.
- To date, due to technical advances, cancer research is producing information at an incredibly rapid pace, challenging even the most tech-competent physicians to use these data to significantly improve patient care. But in the near future, AI will help us make connections among all the data needed to answer a complex medical question in a very short time, reducing both the costs of the technology and the costs of treatments.
- CAR-T is arriving in the field of solid tumours and for lung cancers too. This will be the next frontier, even if we are struggling because CAR-T cells do not enter a solid tumour, but they can act to modulate the immune response. I’m expecting to see new drugs based on CAR-T technology for lung, ovary, and mesothelioma (currently in phase 1 trials) in a few years.