Erlotinib in Conditions of Routine Clinical Practice

Position of Erlotinib in the Treatment of NSCLC

Erlotinib is one of the options for the 1st line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an activating mutation in the EGFR gene. In the 2nd and subsequent lines of treatment, it can be used if it was not part of the previous treatment and in the absence of the EGFR T790M mutation, which is the most common cause of failure of anti-EGFR targeted therapy with 1st generation tyrosine kinase inhibitors (TKI).

In phase II and III clinical trials, TKIs provided clinical benefits to patients – prolonging progression-free survival (PFS) in any line of treatment. However, many studies did not show an extension of overall survival (OS) because their design allowed switching to another therapy or using TKI in later lines of treatment for ethical reasons. Therefore, it is important to study the efficacy of anticancer drugs in real-world clinical practice conditions through observational studies.

Efficacy and Tolerance in a Non-Selected Population

One such study was conducted by French pulmonologists. They selected patients with advanced or metastatic NSCLC with an activating EGFR mutation from the medical records of 44 doctors who started erlotinib treatment between April 2014 and March 2016 and studied their records from the following 2 years.

In total, data from 177 patients were analyzed, with a median age of 72 years. Most of them never smoked (63.3%) and were predominantly women (69.5%). At the time of study entry, 22.6% of patients had brain metastases and 42.4% had undergone initial treatment for NSCLC (surgical, pharmacological/chemotherapy, but not targeted TKI therapy, radiotherapy).

Survival and Treatment Response

The median PFS in this population was 11.7 months. After 1 year, 48.6% of patients were progression-free (95% confidence interval [CI] 41.5–57.0%). The median OS was 25.8 months and after 1 year, 74% of patients were alive (95% CI 68–82%).

After 1 year, 4 patients (3.9%) achieved complete remission, 15 (14.7%) responded partially, and 52 (51%) had stabilized disease. After 2 years, 4 patients (6.5%) were still in complete remission, 10 (16.1%) in partial remission, and 37 (60%) had stabilized disease.

Poor performance status increased the risk of death, but not smoking or the presence of brain metastases. Weight gain during treatment proved to be a favorable factor – as with all patients with solid tumors, it is essential to take care of their nutritional status.

Safety Profile

No unusual safety signals were detected in the study. During the first 6 months of treatment, grade 3 and 4 adverse events occurred in 6 (7.7%) patients. Most (69.6%) were prescribed preventive measures against side effects or these complications were adequately treated if they occurred.

Conclusion

The observed population was older, frailer, and with poorer performance status than the populations included in previous phase III clinical trials. Nevertheless, the efficacy and safety of erlotinib were confirmed, and the PFS and OS results were comparable or even more favorable compared to some studies. The authors attribute this to better management of side effects.

(jam)

Sources:
1. The Blue Book of the Czech Oncology Society, 28th update. Masaryk Oncology Institute, Brno, March 1, 2022. Available at: www.linkos.cz/lekar-a-multidisciplinarni-tym/personalizovana-onkologie/modra-kniha-cos/aktualni-vydani-modre-knihy
2. Payen T., Trédaniel J., Moreau L. et al. Real world data of efficacy and safety of erlotinib as first-line TKI treatment in EGFR mutation-positive advanced non-small cell lung cancer: results from the EGFR-2013-CPHG study. Respir Med Res 2021; 80: 100795, doi: 10.1016/j.resmer.2020.100795.