Lung Cancer Researchers Gather at #ttlc25

Breakthroughs in NSCLC Treatment: Key Insights from #TTLC25

The Targeted Therapies for Lung Cancer (#TTLC25) conference showcased groundbreaking advancements across multiple facets of non-small cell lung cancer (NSCLC) treatment. Experts delved into critical topics, including optimizing treatment sequencing for EGFR-mutated NSCLC, emerging immunotherapies, rare molecular subtypes, and novel therapeutic approaches. Here are the most impactful insights shaping the future of lung cancer care.

Optimizing Treatment Sequencing: Balancing Efficacy and Quality of Life

Dr. Julia Rotow (@JuliaRotow) emphasized that while osimertinib monotherapy remains the standard of care for EGFR+ NSCLC, new data from the FLAURA2 and MARIPOSA trials are challenging existing paradigms. The discussion introduced the concept of "time toxicity," which refers to the often-overlooked burden of intensive treatment regimens on patients' daily lives. Notably, 25-40% of patients never reach second-line therapy, making first-line treatment selection critical.

Emerging Immunotherapies: Oncolytic Viruses and Novel Targets

Dr. Ana V. Manana (@AnaVManana) explored the potential of oncolytic viruses in combination with immune checkpoint inhibitors, demonstrating promising synergies that are still in early clinical stages.

Additionally, Dr. Justin Gainor (@justingainor) presented emerging oncogene-directed immunotherapies, such as peptide and mRNA vaccines for ALK+ NSCLC, as well as innovative strategies targeting macrophages via CD47 inhibitors.

Addressing Rare Molecular Subtypes: EGFR PACC Mutations

Dr. Le Xiuning (@LeXiuning) provided valuable insights into EGFR PACC mutations, which constitute approximately 12% of EGFR+ NSCLC cases. Current treatment options show heterogeneous efficacy, with afatinib offering the most promising responses. Ongoing trials, including firmonertinib in first-line and adjuvant settings, aim to refine treatment strategies for these rare variants.

The Potential of Antibody-Drug Conjugates (ADCs)

Dr. Tim Yap (from @MDAndersonNews) outlined the growing role of ADCs in NSCLC treatment, focusing on key extracellular targets such as tissue factor, Nectin-4, FRα, CEACAM5, NaPi2B, and ROR2. These ADCs, many of which have received FDA approval in other cancer types, may offer new therapeutic avenues for patients with limited treatment options.

The Role of Biomarkers in Personalizing Therapy

Dr. Ferdinandos Skoulidis (@FSkoulidis) stressed the clinical impact of STK11 and KEAP1 mutations. STK11 alterations negatively affect response to single-agent anti-PD-(L)1 therapies, while KEAP1 mutations contribute to resistance against platinum-based chemotherapy. These findings reinforce the growing importance of molecular profiling in treatment selection.

ALK+ NSCLC: Improving Risk Stratification and Patient Outcomes

Dr. Tejas Patil (@TejasPatilMD) discussed risk stratification for ALK+ NSCLC, highlighting molecular predictors of poor outcomes with ALK TKIs. He emphasized the need for personalized approaches, intensification strategies to address drug-tolerant persister cells, and greater focus on quality of life considerations.

Young Lung Cancer: Addressing Unique Challenges

Dr. Coral Olazagasti (@COlazagasti) and Dr. Narjust Florez (@NarjustFlorezMD) brought attention to the rising incidence of lung cancer in younger patients, particularly women.

Their presentations covered key issues such as delayed diagnosis, survivorship challenges, fertility concerns, and financial toxicity, underscoring the need for tailored interventions.

Ivonescimab: Exciting Potential, but Data Gaps Remain

One of the most talked-about therapies at #TTLC25 was ivonescimab, an IO/VEGF inhibitor from the HARMONi-2 trial. Dr. Balasz Halmos (@BalazsHalmosMD) sparked debate by presenting the potential of this new therapy while also highlighting existing data gaps that need further exploration.

Looking Forward: The Future of NSCLC Treatment

As Dr. Eric Singhi (@lungoncdoc) noted, shared decision-making is more critical than ever in navigating the increasingly complex EGFR+ NSCLC treatment landscape. With rapid advancements in targeted therapy, immunotherapy, and molecular profiling, a patient-centric approach that considers both efficacy and quality of life is essential.

For access to all presentations, visit the IASLC’s Lung Cancer 360 portal: Lung Cancer 360.

Stay tuned for further updates as these evolving therapies continue to shape the future of lung cancer treatment.