EGFR mutation accounted for 10%-15% of the NSCLC cases in European and Caucasian populations. In Asian nations, the prevalence is high. Roughly 40%-50% of Asian patients with NSCLC have the EGFR mutation at diagnosis. EGFR inhibitors are the main standard of care in this segment. TAGRISSO is the only targeted therapy that has shown survival benefits in both early- and late-stages of EGFR-mutated NSCLC. It is approved as a single-agent treatment in over 100 countries, including the US, EU, China, and Japan. These approvals cover the first-line treatment of patients with locally advanced or metastatic EGFRm NSCLC (FLAURA), locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage (IB, II, and IIIA) EGFRm NSCLC (ADAURA), where TAGRISSO recently showed a significant and meaningful OS advantage. AstraZeneca is testing osimertinib in combination with chemotherapy in the FLAURA2 Phase III trial.

According to FLAURA2 results, patients who received a combination of osimertinib and chemotherapy had a 9% estimated risk of developing a central nervous system (CNS) lesion at the 24-month mark, with a confidence interval (CI) ranging from 4% to 16%. In contrast, those who received osimertinib as a standalone treatment had a higher estimated risk of 23% (with a 95% CI between 14% and 33%) for developing a CNS lesion.

Furthermore, when compared to osimertinib alone, the addition of chemotherapy to the EGFR tyrosine kinase inhibitor (TKI) led to a notably improved CNS objective response rate (ORR) and an enhanced rate of complete responses (CR). These responses were durable over time, and the safety profile remained manageable and well-tolerated.

It is worth noting that the combined therapy group reported more cases of grade 3 or more severe adverse events, with hematological toxicities being the most commonly reported. Additionally, interstitial lung disease occurred in 3% of patients in the combination group and 4% in the monotherapy group. These toxicities were most frequent and severe during the initial treatment period but gradually subsided over time.

KOL insights

“In the randomized trials like FLAURA2 and MARIPOSA, I agree we should be able to look in the control arm and confirm good/bad actors. Then look between control and experimental arm in the same group for suggestion if the impact of intervention is the same or not by these factors.” – Oncologist, US

Conclusion

NSCLC is increasingly becoming a biomarker-driven market. EGFR is one of the profitable biomarker segments, with blockbuster therapies such as TAGRISSO. TAGRISSO is now the dominant EGFR inhibitor selling nearly USD 6 billion in 2022. The prevalence of patients with this resistance mutation has increased since TAGRISSO was authorized for use in the first line. The post-TAGRISSO setting is one of the highest areas of unmet need.

TAGRISSO could face competition from  RYBREVANT, which is running several trials using lazertinib, a third-generation EGFR inhibitor, to get access to a bigger patient cohort through the MARIPOSA, MARIPOSA-2, and CHRYSALIS-2 investigations. To capture the greater pool in EGFR NSCLC mutation, RYBREVANT, as a subcutaneous formulation, is also undertaking a sequence of PALOMA studies in combination with lazertinib. It is crucial to remember that RYBREVANT can find it difficult to defeat TAGRISSO.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Epidermal Growth Factor Receptor-Non Small Cell Lung Cancer (EGFR-NSCLC) Market Insight and Market Forecast Report

Note: The therapeutics segment is experiencing significant NSCLC clinical trial activity, which is further expected to drive Non-Small Cell Lung Caner market growth in the coming years.