Treatment with aumolertinib was associated with prolonged survival and duration of response in patients with non–small cell lung cancer.
Compared with gefitinib (Iressa), aumolertinib improved progression-free survival (PFS) and duration of response (DOR) in patients with advanced non–small cell lung cancer (NSCLC) with EGFR, according to findings presented at the virtual 2021 ASCO Annual Meeting.
“Based on these results, we will pursue discussions with global regulatory authorities; we anticipate our development approach will facilitate a markedly less costly global access pricing structure,” said Shun Lu, MD, PhD, from the Shanghai Lung Cancer Center, Shanghai Chest Hospital at Shanghai JiaoTong University, in the presentation.
Aumolertinib is an irreversible EGFR TKI that has already been approved in China for patients with EGFR-mutant NSCLC when disease has progressed and has favorable pharmacologic properties that inhibit EGFR sensitizing and resisting mutations.
This phase 3 trial assessed the safety and efficacy of treatment with aumolertinib compared with gefitinib in 429 patients across China who had previously untreated metastatic or locally advanced NSCLC and EGFR exon 19 deletion or L858R. Patients were randomly assigned to received either aumolertinib, once per day at 110mg (n= 214; median age, 59 years), or gefitinib, once per day at 250 mg (n = 215; median age, 62 years). Researchers had a primary endpoint of PFS, and secondary endpoints of overall survival (OS), objective response rate (ORR), DOR and safety. With 262 PFS events the study had 90% power to detect PFS (HR = 0.67).
Median PFS was significantly prolonged with aumolertinib at a median of 19.3 months (HR = 0.46; 95% CI, 17.8-20.8; P < 0.0001) compared with gefitinib at 9.9 moths (HR = 0.46; 95% CI, 8.3-12.6; P < 0.0001).
Median DOR followed a similar trend and was also significantly prolonged by aumolertinib at 18.1 months (HR = 0.38; 95% CI, 15.2-NA; P < 0.0001) compared with gefitinib at 8.3 months (HR = 0.38; 95% CI, 6.9-11.1; P < 0.0001). ORR was 73.8% with aumolertinib and 72.1% with gefitinib. And median overall survival was not reached.
Although aumolertinib was a longer treatment time compared with gefitinib, 463 days vs 254 days, side effects such as rash, diarrhea, alanine aminotransferase/ aspartate aminotransferase increase were less likely in that group.
The most common adverse events included alanine aminotransferase increased (29.4% in the aumolertinib arm vs 55.8% in the gefitinib arm), aspartate aminotransferase increased (29.9% vs 54%, respectively), rash (23.4%, vs 41.4%), diarrhea (16.4% vs 35.8%) and creatine phosphokinase (CPK) increased (35.5% vs 9.3%).
Additionally, aumolertinib was also associated with CPK increase, platelet count decrease and neutrophil count decrease.
Further research evaluating aumolertinib with other treatments is either ongoing or planned, Lu noted.
Lu S, Dong X, Jian H, et al. Randomized Phase III Trial of Aumolertinib (HS-10296, Au) Versus Gefitinib (G) as First-Line Treatment of Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) and EGFR Exon 19 Del or L858R mutations (EGFRm). J Clin Oncol. 2021;39(suppl 15):Abstract 9013.