ASCO 2023

Predictive biomarkers of efficacy in targeted combination therapy for metastatic lung cancer with EGFR mutation

The CHRYSALIS 2 trial, presented orally at this year's ASCO conference by Pr. Benjamin Besse, Director of Clinical Research at Gustave Roussy, focused on patients with metastatic lung cancer with an EGFR mutation. The results indicate that in the case of failure of first-line treatment with osimertinib, the combination of amivantamab, a new intravenously administered targeted therapy, and lazertinib, an oral EGFR inhibitor, yields favorable results when the tumor overexpresses the MET protein.

Abstract number 9013 presented by Pr. Benjamin Besse on Friday, June 2.

The EGFR gene mutation is present in 10 to 15% of cases of lung cancer in individuals of Caucasian origin (often non-smokers) and in nearly 50% of cases in Asia.

The standard first-line treatment for metastatic lung cancer with this mutation is osimertinib, a third-generation targeted therapy inhibiting EGFR. This standard may be challenged this year at ASCO with the results of the FLAURA 2 study, which compares osimertinib alone as first-line treatment to osimertinib combined with chemotherapy. "If promising results are demonstrated, this could become the new standard treatment for these patients" explains Pr. Benjamin Besse, Director of Clinical Research at Gustave Roussy and principal investigator of the CHRYSALIS-2 study.

Furthermore, the MARIPOSA trial compares osimertinib alone to a combination of two targeted therapies, amivantamab and lazertinib. Its results could indicate another treatment standard.

In this context, it is important to better understand, through tumor analysis, which patients could derive the most benefit from each treatment. This is the goal of the CHRYSALIS-2 study presented at ASCO this year.

Predicting efficacy to guide the best treatment

This phase 1-2 study investigates the therapeutic combination of amivantamab/lazertinib. Pr. Benjamin Besse presents the results of a new homogeneous cohort of patients who received osimertinib as first-line treatment before experiencing treatment failure. The combination of the two targeted therapies, amivantamab/lazertinib, was then offered to them. The initial results of the CHRYSALIS trial showed a response rate of 36% with this combination therapy in metastatic lung cancer with the EGFR mutation. "Our new cohort of 108 patients confirms a response rate of 30%, with an average response duration of 10.8 months" emphasizes Pr. Besse, for whom this combination proves to be "an interesting salvage treatment after osimertinib failure, albeit with non-negligible toxicity."

In this new cohort, all patients underwent tumor biopsies before receiving amivantamab/lazertinib, allowing, among other things, the measurement of MET protein expression. "Thanks to these biopsies, we were able to see that 36% of patients had a tumor with MET overexpression. For these patients, the response rate reached 61% with the amivantamab/lazertinib combination, compared to 14% when MET was not overexpressed. The median progression-free survival is 12.2 months versus 4.2 months."

MET protein expression proves to be particularly predictive of the efficacy of this bispecific antibody combination. This information could help select the most effective medication if, in the future, multiple treatment standards were available for patients with EGFR-mutated lung cancer.