Improvement of EGFR Testing over the Last Decade and Impact of Delaying TKI Initiation

Abstract

Background: Epidermal growth factor receptor (EGFR) is the most common oncogenic mutation in lung adenocarcinoma and tyrosine kinase inhibitors (TKIs) have been considered standard treatment for more than a decade. However, time to initiation of TKIs (TTIT) from diagnosis is often delayed and represents a challenge for clinicians. We aimed to assess the impact of TTIT on clinical outcomes and complications. Method: TTIT was defined as the time between confirmed advanced diagnosis and the initiation of a TKI. Complications during this pre-TKI period were retrospectively collected from all patients with EGFR-mutant non small cell lung cancer (NSCLC) in our institution. Results: 102 patients were diagnosed with EGFR mutated NSCLC between 2006 and 2019. The median PFS and OS were 12.9 and 22.5 months, respectively. TTIT was 5.7 months (95% CI 3.4–8) with a significant decrease in the latter years of this cohort. During the pre-TKI period, 23 patients received chemotherapy as first line treatment, of which 5 developed severe adverse events and 3 were not fit to receive TKI thereafter. Additionally, 29 patients had rapid clinical deterioration before initiation of first line TKI and 16 had to be hospitalized. Among the patients presenting a performance status deterioration, their prognosis was markedly affected compared to the remainder of the cohort (p = 0.01). Conclusion: Our real-world evidence study supports the concept that a delay to treat EGFR mutant NSCLC with TKIs is associated with adverse events, patient progression, hospitalization, and decreased overall survival. Rapid molecular diagnosis, including access to ctDNA technology may circumvent these deleterious delays.

Contribution of the IdyllaTM System to Improving the Therapeutic Care of Patients with NSCLC through Early Screening of EGFR Mutations

“…For patients with metastatic NSCLC harboring EGFR mutations, the development of EGFR tyrosine kinase inhibitors (TKIs) is an important improvement in therapeutic care, as shown by the increase in the progression-free survival (PFS) and limitation of toxicities using EGFR-TKIs for patients with EGFR -mutated NSCLC compared to chemotherapy [ 5 ], especially with the use of osimertinib versus first-line TKIs (gefitinib and erlotinib) [ 4 , 6 ]. However, a long delay to initiate EGFR-TKIs can result in rapid disease progression and deterioration in performance status associated with a worse prognosis [ 45 ]. Thus, it is essential to accelerate the availability of molecular sub-type results.…”