Leclaza (lazertinib), a new lung cancer drug developed by Yuhan Corporation, has been officially included in the European Society for Medical Oncology (ESMO) guidelines.

Reflecting the latest clinical study findings, Leclaza in combination with Rybrevant (amivantamab, Johnson & Johnson) has been included as a first-line option in the guidelines.

#According to industry sources on the 30th, the European Society for Medical Oncology recently updated and announced its “Living Guidelines” for advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

The ESMO Living Guidelines, which reflect the latest research findings, evaluate treatment options based on the ESMO-MCBS (ESMO Magnitude of Clinical Benefit Scale, a tool for assessing the value of anticancer drugs) score and the ESCAT (ESMO Scale for Clinical Actionability of Molecular Targets, a scale for ranking the clinical relevance of genetic mutations as targets for cancer treatment) mutation-drug matching score.

Accordingly, the Living Guidelines included the combination therapy of Leclaza and Rybrevant as a first-line treatment option, along with Tagrisso (osimertinib) monotherapy and Tagrisso+chemotherapy.

This can be seen as a reflection of the results of the Phase III MARIPOSA study released at the European Lung Cancer Congress (ELCC) in March.

According to the MARIPOSA Phase III study, the risk of death was reduced by 25% in the Leclaza-Rybrevant combination therapy group compared with the Tagrisso (osimertinib, AstraZeneca) monotherapy group (HR=0.75, 95% CI: 0.61–0.92, P<0.005). The median overall survival (mOS) in the combination therapy group was not reached and was analyzed as not estimable (95% CI: 42.9–NE), while the Tagrisso group was 36.7 months (95% CI: 33.4–41.0).

In particular, a significant difference was observed in the 3-year survival rate at 36 months. The combination therapy group’s 3-year survival rate was 60%, with the Tagrisso group’s being 51%.

At 42 months, the difference between the two control groups widened to 56% and 44%, respectively, suggesting the greater clinical benefit of Leclaza-Rybrevant.

However, in the ESMO-MCBS score presented in the Living Guidelines, the Leclaza and Rybrevant combination was rated as ‘MCBS 3’. The same applied to the Tagrisso and chemotherapy combination.

Tagrisso monotherapy was assigned an MCBS score of 4.

Nevertheless, the Living Guidelines clearly state that the combination therapy of Leclaza and Rybrevant provided significant progression-free survival (PFS) and overall survival (OS) benefits compared to Tagrisso monotherapy.

The Living Guidelines state, “In the Phase III MARIPOSA study, the combination of Leclaza and Rybrevant provided significant PFS and OS benefits compared to Tagrisso monotherapy, In FLAURA-2, the combination of Tagrisso and chemotherapy significantly increased PFS compared to monotherapy. These provide benefits for patients with brain metastases.”