On the first day of the 2023 European Lung Cancer Congress (ELCC), during the oral presentation session, P. Garrido Lopez from Ramón y Cajal University Hospital in Madrid, Spain, presented the long-term efficacy, safety, and predictive factors of amivantamab in the treatment of platinum-treated EGFR exon 20 insertion (EGFR ex20ins) mutant advanced non-small cell lung cancer (NSCLC) patients in the CHRYSALIS trial (Abstract No. 3O). In an interview with "Tumor Insight," P. Garrido Lopez further elucidated the results of the CHRYSALIS trial and its clinical significance.
What research data and reports from ELCC 2023 have you found most interesting?
P. Garrido Lopez: The 2023 ELCC Congress has already provided some updates, including the Proffered Paper 1 oral presentation, which updated the results of the CHRYSALIS study in which I was involved. Another report that I find particularly interesting is the Phase III CodeBreaK 200 trial, which assesses the quality of life (QoL) outcomes of the KRAS G12C inhibitor Sotorasib compared to docetaxel as a second-line treatment for NSCLC patients carrying KRAS G12C mutations. I believe ELCC meetings usually emphasize the educational component, and there are many intriguing sessions. In the "Controversy session" on the second day of the conference, experts debated whether neoadjuvant immunotherapy is superior to adjuvant immunotherapy, and on March 30th, the educational session focused on "Mechanisms of Resistance to Immunotherapy and Targeted Agents."
I presented the updated results of the CHRYSALIS study at this conference, which involved the use of amivantamab to treat platinum-treated EGFR exon 20 insertion (EGFR ex20ins) mutant advanced NSCLC patients. Besides the two common EGFR mutations (exon 19 deletions and exon 21 L858R mutations), there is a third important EGFR mutation, the EGFR exon 20 insertion mutation, which accounts for approximately 12% of EGFR-positive NSCLC cases. For the subset of patients with EGFR exon 20 insertion mutations, the available targeted treatment options are the monoclonal antibody amivantamab and the oral TKI drug mobocertinib. Based on the CHRYSALIS study data, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved amivantamab for the treatment of platinum-refractory EGFR exon 20 insertion mutant metastatic NSCLC patients.
In my presentation at this conference, I showcased the long-term results of the CHRYSALIS study. Among 114 EGFR exon 20 insertion mutant NSCLC patients who had progressed after platinum-based chemotherapy, amivantamab achieved a median overall survival (OS) of 23 months (95% confidence interval [CI]: 18.5-29.5). 47.2% of patients survived for more than 2 years. At the data cutoff, 15 patients were still on treatment, indicating they had been receiving amivantamab for over 2 years (median treatment duration of 2.6 years). These data hold clinical relevance. Moreover, the long-term follow-up showed that drug toxicity was not significantly different from what had been previously reported, implying that most adverse events (AEs) are infusion-related reactions, rash, paronychia, etc., and these AEs predominantly occur in the first cycle. The CHRYSALIS study data provide a new opportunity for the treatment of EGFR exon 20 insertion mutant NSCLC patients, adding a monoclonal antibody-based treatment option.
Safety
The management of immune-related adverse events (irAEs) is a matter of clinical concern. Could you share some insights into managing irAEs?
P. Garrido Lopez: The management of irAEs is crucial. Although immune checkpoint inhibitors have lower toxicity compared to chemotherapy, some patients still experience immune-related adverse events. Clinical physicians need to anticipate this before implementing treatment. We can refer to guidelines for the management of immune-related adverse events, such as the "ESMO Clinical Practice Guidelines: Diagnosis, Treatment, and Management of Immune-Related Adverse Events." These guidelines provide references for managing patients who experience irAEs. Some irAEs are quite common and easy to handle, while dealing with conditions like pneumonitis or hepatitis might be more complex and require close monitoring and differentiation. We use corticosteroids to treat irAEs, considering that some immune-related toxicities can be severe. The key is to detect irAEs promptly and initiate treatment as quickly as possible.
What research data and reports from ELCC 2023 have you found most interesting?
P. Garrido Lopez: The 2023 ELCC Congress has already provided some updates, including the Proffered Paper 1 oral presentation, which updated the results of the CHRYSALIS study in which I was involved. Another report that I find particularly interesting is the Phase III CodeBreaK 200 trial, which assesses the quality of life (QoL) outcomes of the KRAS G12C inhibitor Sotorasib compared to docetaxel as a second-line treatment for NSCLC patients carrying KRAS G12C mutations. I believe ELCC meetings usually emphasize the educational component, and there are many intriguing sessions. In the "Controversy session" on the second day of the conference, experts debated whether neoadjuvant immunotherapy is superior to adjuvant immunotherapy, and on March 30th, the educational session focused on "Mechanisms of Resistance to Immunotherapy and Targeted Agents."
I presented the updated results of the CHRYSALIS study at this conference, which involved the use of amivantamab to treat platinum-treated EGFR exon 20 insertion (EGFR ex20ins) mutant advanced NSCLC patients. Besides the two common EGFR mutations (exon 19 deletions and exon 21 L858R mutations), there is a third important EGFR mutation, the EGFR exon 20 insertion mutation, which accounts for approximately 12% of EGFR-positive NSCLC cases. For the subset of patients with EGFR exon 20 insertion mutations, the available targeted treatment options are the monoclonal antibody amivantamab and the oral TKI drug mobocertinib. Based on the CHRYSALIS study data, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved amivantamab for the treatment of platinum-refractory EGFR exon 20 insertion mutant metastatic NSCLC patients.
In my presentation at this conference, I showcased the long-term results of the CHRYSALIS study. Among 114 EGFR exon 20 insertion mutant NSCLC patients who had progressed after platinum-based chemotherapy, amivantamab achieved a median overall survival (OS) of 23 months (95% confidence interval [CI]: 18.5-29.5). 47.2% of patients survived for more than 2 years. At the data cutoff, 15 patients were still on treatment, indicating they had been receiving amivantamab for over 2 years (median treatment duration of 2.6 years). These data hold clinical relevance. Moreover, the long-term follow-up showed that drug toxicity was not significantly different from what had been previously reported, implying that most adverse events (AEs) are infusion-related reactions, rash, paronychia, etc., and these AEs predominantly occur in the first cycle. The CHRYSALIS study data provide a new opportunity for the treatment of EGFR exon 20 insertion mutant NSCLC patients, adding a monoclonal antibody-based treatment option.
Safety
The management of immune-related adverse events (irAEs) is a matter of clinical concern. Could you share some insights into managing irAEs?
P. Garrido Lopez: The management of irAEs is crucial. Although immune checkpoint inhibitors have lower toxicity compared to chemotherapy, some patients still experience immune-related adverse events. Clinical physicians need to anticipate this before implementing treatment. We can refer to guidelines for the management of immune-related adverse events, such as the "ESMO Clinical Practice Guidelines: Diagnosis, Treatment, and Management of Immune-Related Adverse Events." These guidelines provide references for managing patients who experience irAEs. Some irAEs are quite common and easy to handle, while dealing with conditions like pneumonitis or hepatitis might be more complex and require close monitoring and differentiation. We use corticosteroids to treat irAEs, considering that some immune-related toxicities can be severe. The key is to detect irAEs promptly and initiate treatment as quickly as possible.