1328P Analysis of data from the AENEAS study assessing the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), aumolertinib, and virtual comparison with osimertinib

TKIs targeting the EGFR revolutionized care of patients (pts) with non-small cell lung cancer (NSCLC) harboring EGFR mutations. Resistance to 1st/2nd-generation EGFR TKIs inevitably develops, with clone(s) harboring T790M EGFR mutations emerging in 50–70% of cases. 3rd-generation EGFR TKIs active against T790M and common EGFR-activating mutations are in development; only osimertinib and aumolertinib have regulatory approvals. We have described a novel approach for assessing treatment efficacy using measurements of tumor burden to estimate rates of growth and regression of tumors designated g and d, respectively. Data from thousands of pts with diverse tumors have shown g is inversely correlated with OS. We analyzed data from the randomized phase III AENEAS study comparing aumolertinib with gefitinib. 94% of the data could be analyzed; notably more pts than included for the primary PFS endpoint. Tumor growth reflected in a detectable g was found in 89% of both arms, including many not scored as progression. Superiority of aumolertinib was evident in statistically slower g values [and longer tumor doubling times, TDT] for aumolertinib [g = 0.0006/day (0.0005-0.0011); TDT 1155 days] than gefitinib, [g = 0.0012/day (0.0007-0.0020); TDT, 578 days], p<0.0001. Aumolertinib was superior in slowing g in tumors with Ex19del alterations compared to L858R mutations [p=0.0018], and superior to gefitinib in slowing g in tumors with Ex19del alterations [p<0.0001] just missing significance for L858R mutations [p=0.0687] – possibly due to smaller number of pts. Aumolertinib slowed g in non-smokers compared to smokers [p=0.0066] and superior to gefitinib in slowing g in non-smokers [p<0.0001]. Finally, g values with aumolertinib were comparable to published osimertinib values.Table: 1328PMedian rate of tumor growth (g) by line and type of therapyLine of therapyType of therapyNMedian g/dayTumor Doubling TimeData from USFDA Analysis [Gong, ASCO 2020]FrontMono 1stGen EGFRi*2370.0012/day578 daysFrontOsimertinib2430.0007/day990 daysData from analysis of AENEAS studyFrontGefitinib2150.0012/day578 daysFrontAumolertinib2140.0006/day1155 days*1st generation EGFR inhibitors, gefitinib or erlotinib Open table in a new tab *1st generation EGFR inhibitors, gefitinib or erlotinib Like osimertinib, aumolertinib is a highly effective third-generation EGFR-TKI.