ESMO Congress 2024 Round-up

New Data on EGFR Treatments

At the ESMO Congress 2024, exciting new data on targeted therapies for EGFR-mutant advanced non-small cell lung cancer (NSCLC) was presented, showcasing promising treatment options for patients who have developed resistance to their initial treatment. A key focus was on understanding resistance mechanisms to improve outcomes, and increase survival rates.

The MARIPOSA trial highlighted that combining amivantamab with lazertinib significantly reduced the development of treatment resistance compared to osimertinib, suggesting that this dual-targeted therapy may offer better long-term control. Additionally, data from the MARIPOSA-2 study confirmed that amivantamab combined with chemotherapy improved survival rates after progression on osimertinib, outperforming standard chemotherapy alone. While we are still waiting for the final overall survival data from this trail, so far this is looking like a very promising treatment regimen. However, it was acknowledged that better management of toxicity, especially skin toxicity, is needed for this treatment.

New data from the REZILIENT1 phase II clinical trial was also presented, shedding light on the potential of zipalertinib, a selective EGFR tyrosine kinase inhibitor (TKI), for patients with EGFR exon 20 mutations. In a group of 30 patients (who had previously received amivantamab), zipalertinib demonstrated a good response rate, with manageable toxicity opening up a new potential treatment pathway in the future. These promising results suggest zipalertinib could be a strong treatment option, even after disease progression on other targeted therapies. This new evidence brings hope for Exon 20 patients, who currently have limited treatment options in the UK

Across several studies presented, one key theme that came up was having better long-term goals in the future. As targeted agents continue to advance, a key focus should be to refine knowledge about how best to sequence the different available treatments to improve patient outcomes and extend survival.

Liquid biopsy

Lung cancer treatment is making strides with the use of liquid biopsy, which offers new hope in early detection and management. A liquid biopsy is a simple blood test that looks for small pieces of DNA from cancer cells in your blood. These cancer cells are called circulating tumour DNA, or ctDNA. By looking at these DNA pieces, it is possible to identify any changes that have occurred in the genetic make-up of the cancer, which might be driving its development. This can help to quickly identify patients who might benefit from targeted treatments, and better guide treatment decisions.

At the ESMO Congress 2024, several studies highlighted the important role that ctDNA can play in monitoring disease, predicting treatment outcomes, and detecting relapse risk sooner than traditional imaging. For instance, studies by van den Heuvel et al. and Wakelee et al. showed that ctDNA can predict treatment outcomes and survival in post-operative and chemotherapy settings (Abstract 1226P, 1211P). Additionally, the ctDNA-Lung-Detect study provided further insights into ctDNA's value, showing its association with survival in patients with early-stage, resected non-small cell lung cancer (NSCLC) (Abstract 1236P). Together, these findings underscore the growing importance of liquid biopsy in lung cancer, and we hope to see them more routinely used in standard care in the future.

Professor Gini Harrison, Research Trustee

References

Besse B, et al. Mechanisms of acquired resistance to first-line amivantamab plus lazertinib versus osimertinib in patients with EGFR-mutant advanced non-small cell lung cancer: An early analysis from the phase 3 MARIPOSA Study. ESMO Congress 2024, LBA55

Khan S, et al. ctDNA-Lung-Detect: Profiling of non-shedding ctDNA early stage resected non-small cell lung cancers. ESMO Congress 2024, Abstract 1236P

Passaro A, et al. Safety and antitumor activity of zipalertinib in NSCLC patients (pts) with EGFR exon 20 insertion (ex20ins) mutations who received prior amivantamab. ESMO Congress 2024, Abstract 1254MO

Popat S, et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non-small cell lung cancer after disease progression on osimertinib: 2nd interim overall survival from MARIPOSA-2. ESMO Congress 2024, LBA54

van den Heuvel M, et al. Predictive value of circulating tumor DNA (ctDNA) before and shortly after curative treatment in early-stage non-small cell lung cancer (NSCLC), and exploration of (pre-)analytical factors. ESMO Congress 2024, Abstract 1226P

Wakelee H, et al. IMpower010: ctDNA status and 5y DFS follow up in patients (pts) with resected NSCLC who received adjuvant chemotherapy (chemo) followed by atezolizumab (atezo) or best supportive care (BSC). ESMO Congress 2024, Abstract 1211P