Aptitude Health recently spoke with Enriqueta Felip, MD, PhD, section chief at the Vall d’Hebron University Hospital, head of the Vall d’Hebron Institute of Oncology’s Thoracic Tumors Group in Barcelona, Spain, and a professor of medicine at the Universitat Autònoma de Barcelona. Her research focuses on accelerating more-effective personalized and targeted cancer medicines matched to specific molecular alterations identified in patients, unmasking molecular mechanisms of acquired cancer drug resistance, and optimizing immune-based strategies in both advanced and early-stage non-small cell lung cancer (NSCLC).
Dr Felip served as president (2021–2023) of the Spanish Society of Medical Oncology (SEOM) and was an elected member of the board of directors of the International Association for the Study of Lung Cancer (IASLC) from 2017–2021. She has been a member of the Educational and Scientific Committees of the European Society for Medical Oncology (ESMO), World Conference on Lung Cancer (WCLC), and European Lung Cancer Congress (ELCC). Dr Felip has also lent her expertise to several scientific organizations. These appointments include subject editor of the guidelines working group of ESMO Minimum Clinical Recommendations in lung cancer (2006–2014) and coordinator of the 1st ESMO Consensus Conference on lung cancer. In 2015, she received the first ESMO Women for Oncology Award. Dr Felip was co-chair of the IASLC 20th WCLC in Barcelona in 2019. She is presently a member of the scientific committees of the Spanish Lung Cancer Group (SLCG) and the European Thoracic Oncology Platform (ETOP). Dr Felip serves on the editorial boards of various top-tier journals, including Annals of Oncology and the Journal of Thoracic Oncology. She has (co)authored approximately 400 peer-reviewed papers with an h-index of 94.
Here is a recap of our conversation:
What recent advancements in the management of NSCLC do you consider the most relevant to clinical practice?
The most relevant advancement is the use of molecular profiling and precision medicine in non-small cell lung cancer management. There are numerous patients diagnosed with NSCLC—mostly lung adenocarcinomas—that harbors actionable genomic alterations for whom targeted agents are effective, including EGFR, ALK, ROS1, RET, MET exon 14 skipping, HER2, KRAS G12C, ERBB2, and BRAF V600E.
Another important advancement is immune checkpoint inhibitors, which have shown a clear benefit in the treatment of patients with NSCLC and are now being used as first-line treatment in stage IV, as consolidation therapy following chemo- and immuno-oncology therapy for unresectable stage III disease, and also as neoadjuvant and adjuvant therapy in patients with resectable disease without oncogenic alterations. Additionally, adjuvant targeted therapies have a role in completely resected early-stage NSCLC when EGFR or ALK alterations are present.
Given the progress in comprehending gene mutations and biomarkers, what is your perspective on how these findings will shape the future of NSCLC diagnostics and treatment in Europe, particularly with the decreasing size of target populations and the rising cost of diagnostic panels?
At present, biomarker testing is needed not only in metastatic disease, but also in early-stage NSCLC to guide treatment decisions. I think ensuring the implementation of biomarker determination in clinical practice is essential. The recommendations of the scientific societies are clear. In 2020, ESMO recommended molecular testing using next-generation sequencing [NGS] technologies for relevant driver alterations in assessment of NSCLC. ESMO guidelines also reinforce that PD-L1 [programmed cell death protein 1 ligand 1] expression testing is mandatory before initiating treatment in NSCLC. I think soon it will be necessary to implement large cell panel NGS for all patients with NSCLC to enable testing for all clinically relevant biomarkers.
I also anticipate liquid biopsy and circulating tumor DNA [ctDNA] determination will soon be integrated into clinical practice for predicting minimal residual disease. We may use ctDNA to determine the mechanisms of acquired resistance for some patients with oncogenic alterations with progression after targeted agents.
What remains an unmet need in the treatment of NSCLC, and what areas of future research do you think would be valuable in advancing the field?
I think there are several areas that can help to improve the treatment of patients with NSCLC. As a society we need to work on prevention; for example, smoking is the biggest cause of lung cancer. Looking ahead, we need to work to ensure access to a large-panel NGS with optimal turnaround times and quality assessment of the determinations, supported by the implementation of multidisciplinary molecular tumor boards on a large scale in Europe. In my opinion, education, technology, synergies, and real-world data analyses will be critical pillars for sustaining precision medicine in Europe. Future research should focus on new promising treatment approaches such as antibody-drug conjugates or targeted immunotherapies, and we need to find ways to better identify and meet the needs of lung cancer survivors.
In a recent commentary published in Nature, medical researchers associated with Gustave Roussy and Paris-Saclay University present a forward-thinking perspective on cancer classification. They propose a shift away from the conventional practice of categorizing cancers on the basis of the organ of initial manifestation, to a biological classification based on their molecular characteristics. What benefits do you foresee from adopting a molecular-based classification approach for patients with conventionally categorized lung cancer and for cancer treatment overall?
The reality is that we diagnose smaller and smaller NSCLC populations harboring uncommon molecular alterations that could be treated with targeted drugs. This is a challenge, because when an oncogenic molecular alteration is very uncommon and in different tumor types, conducting clinical trials in each of the specific tumor types may not be feasible and could delay patient access to new drugs. I agree with the Gustave-Paris researchers that classifying cancer according to their molecular characteristics may allow a deeper biological understanding of how cancer works and would also enable access to effective treatments for more patients. As this knowledge progresses, it will be important to analyze patients’ molecular profiles, regardless of cancer type, and redefine the optimal design of clinical trials to get drugs to patients more quickly in subsets of patients with uncommon molecular alterations.
What challenges might healthcare systems face in implementing such a shift in classification, and how quickly do you think such an approach may be implemented in daily clinical practice in Europe?
I think molecular-based classification is the future, but all stakeholders will have to work together to ensure alignment. First, we will need to be able to guarantee molecular testing for all patients. There is also a need to better define the evidence required and establish consensus among all the stakeholders as to whether a specific molecular alteration is important enough to analyze, irrespective of the tumor type. Organizational structure will then need to change, based on the new classification system. Most important is the interpretation of molecular analysis, and I think molecular tumor boards will be essential for that. Lastly, we need more drug approvals based on agnostic histology development.
Considering our conversation today, how do you envision the evolution of NSCLC treatment in Europe over the next 3–5 years?
I think precision medicine will continue to evolve, which may be relevant not only to treatment, but also to earlier diagnosis of patients with lung cancer. We may have screening in people with family history who were never smokers or those with high exposure to air pollution. Comprehensive molecular characterization of cancers will contribute to patients’ access to effective therapies. I expect we will also continue to integrate artificial intelligence [AI] into radiomics and molecular cancer biology and generate AI systems that support further development of precision medicine strategies.