Osimertinib vs Afatinib for NSCLC After EGFR-TKI Treatment Failure

Compared with afatinib, treatment with osimertinib demonstrates better survival outcomes for patients with T790M-positive non-small cell lung cancer (NSCLC) that does not initially respond to initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), according to study results published in BMC Pulmonary Medicine.

A team of investigators in China conducted a retrospective analysis to compare the efficacy of osimertinib vs afatinib in patients with T790M-positive NSCLC and multiple central nervous system (CNS) metastases that did not respond to initial EGFR-TKI treatment.

CT scan of the chest showing advanced stage non-small cell lung cancer (NSCLC), axial section, in a 50 year old woman who had a long history of smoking and emphysema. This large, pleura-based heterogeneous enhancing mass has eroded through the ribs and part of upper thoracic vertebrae. A portion of the right upper lung was removed two years earlier.

Data from 172 patients with T790M-positive NSCLC and multiple CNS metastases were collected from the Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy in Baoding, China from March 2016 to July 2018. Of the 172 patients, 124 patients were included in the final analysis; 60 patients (median age, 62.24 years) were treated with osimertinib and 64 patients (median age, 64.13 years) were treated with afatinib. Demographic data between groups were not statistically significant.

The median duration of follow-up for the total cohort was 24 months, with median follow-up durations of 13.7 months and 9.6 months for patients treated with osimertinib and afatinib, respectively.

Compared with afatinib, patients treated with osimertinib had a significantly longer duration of overall survival (hazard ratio [HR], 0.59; P =.0160). The median duration of progression-free survival was also more favorable for patients treated with osimertinib compared with afatinib (4.5 months vs 3.9 months, respectively; HR, 0.62; P =.014).

 

Adverse events were reported in 80.0% of patients in the osimertinib group and 92.2% of patients in the afatinib group. The frequency of grade 3 or higher adverse events was greater among patients treated with afatinib vs osimertinib (39.4% vs 22.4%, respectively); however, the majority of adverse events were mild to moderate and reversible. Although hematologic toxicity is a significant side effect of EGFR-TKI, the investigators did not report a significant difference in toxicity between the 2 groups.

“We believe that osimertinib could be a more effective therapeutic option than afatinib in the current setting,” wrote the authors. “Although our analysis was powered to assess end-points, given high mortality associated with T790M mutation-positive NSCLC, if osimertinib or afatinib were to be re-evaluated in the comparable setting, extended follow-up time is necessitated to clarify whether our findings persist over an extended follow-up,” they concluded.

Reference
Yang Y, Liu Q, Cao L, et al. Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment. BMC Pulm Med. 2021;21(1):172. doi:10.1186/s12890-021-01539-x